Breast Screening

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)
Breast Cancer
Screening and Diagnosis
Version 1.2023 — June 19, 2023
NCCN.org
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Version 1.2023 , 06/19/23 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
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NCCN Guidelines Version 1.2023 NCCN Guidelines Index

Table of Contents
Breast Cancer Screening and Diagnosis Discussion
*Therese B. Bevers, MD/Chair Þ Jeffrey Hawley, MD ф Liane Philpotts, MD ф

The University of Texas The Ohio State University Comprehensive Yale Cancer Center/Smilow Cancer Hospital
MD Anderson Cancer Center Cancer Center - James Cancer Hospital
and Solove Research Institute Donna Plecha, MD ф
*Mark Helvie, MD/Vice-Chair ф Þ Case Comprehensive Cancer Center/
University of Michigan Linda Hodgkiss, MD ф University Hospitals Seidman Cancer
Rogel Cancer Center St. Jude Children’s Research Hospital/ Center and Cleveland Clinic Taussig
The University of Tennessee Health Cancer Institute
Jennifer L. Baker, MD ¶ Science Center
UCLA Jonsson Comprehensive Cancer Center Jennifer K. Plichta, MD, MS ¶
Tamarya L. Hoyt, MD ф Duke Cancer Institute
Debbie L. Bennett, MD ф Vanderbilt-Ingram Cancer Center
Siteman Cancer Center at Barnes- Shadi Shakeri, MD ф
Jewish Hospital and Washington Jennifer Ivanovich, MS , CGC ₪ UC Davis Comprehensive Cancer Center
University School of Medicine Indiana University Melvin and Bren Simon
Comprehensive Cancer Center Mary Lou Smith, JD, MBA ¥
Ermelinda Bonaccio, MD ф Research Advocacy Network
Roswell Park Comprehensive Cancer Center Maxine S. Jochelson, MD ф
Memorial Sloan Kettering Cancer Center Clarie L. Streibert, MD ф
Melissa S. Camp, MD ¶ Fox Chase Cancer Center
The Sidney Kimmel Comprehensive Swati Kulkarni, MD ¶
Cancer Center at Johns Hopkins Robert H. Lurie Comprehensive Cancer Roberta M. Strigel, MD, MS ф
Center of Northwestern University University of Wisconsin
Sona Chikarmane, MD ф Carbone Cancer Center
Dana-Farber/Brigham and Rachael B. Lancaster, MD ¶
Women’s Cancer Center O'Neal Comprehensive Cancer Center at UAB Lusine Tumyan, MD ф
City of Hope National Medical Center
Emily F. Conant, MD ф Caitlin Mauer, MA, MS, CGC ₪
Abramson Cancer Center UT Southwestern Simmons Nicole S. Winkler, MD ф
at the University of Pennsylvania Comprehensive Cancer Center Huntsman Cancer Institute
at the University of Utah
Mohammad Eghtedari, MD, PhD ф Jessica Maxwell, MD, MS ¶
UC San Diego Moores Cancer Center Fred & Pamela Buffett Cancer Center Dulcy E. Wolverton, MD ф
University of Colorado Cancer Center
Meghan R. Flanagan, MD, MPH ¶ Bethany L. Niell, MD, PhD ф
Fred Hutchinson Cancer Center Moffitt Cancer Center NCCN Guidelines Panel Disclosures
NCCN Bhavika K. Patel, MD ф ф Diagnostic/Interventional ₪ Medical genetics/

Mayo Clinic Comprehensive Cancer Center radiology genomics
Rashmi Kumar, PhD
Ω Gynecologic oncology/ † Medical oncology
Katie Stehman, PA-C, MMS Mark Pearlman, MD Ω ¶ Gynecology ≠ Pathology
Mary Anne Bergman University of Michigan Rogel Cancer Center Þ Internist/Internal ¥ Patient advocacy
medicine, including family ¶ Surgery/Surgical
practice, preventive oncology
Continue management * Discussion Section
Writing Committee

Table of Contents
NCCN Breast Cancer Screening and Diagnosis Panel Members Clinical Trials: NCCN believes that
Summary of the Guidelines Updates the best management for any patient
with cancer is in a clinical trial.
Participation in clinical trials is
Clinical Encounter Including Risk Assessment (BSCR-1) especially encouraged.
Average Risk, Screening/Follow-Up (BSCR-1) Find an NCCN Member Institution:
Increased Risk, Screening/Follow-Up (BSCR-2) https://www.nccn.org/home/member-
Symptomatic During Clinical Encounter, Presenting Signs/Symptoms (BSCR-5) institutions
• Breast Implant-Related Symptoms (BSCR-5) NCCN Categories of Evidence and
• Palpable Symptom (BSCR-6) Consensus: All recommendations
are category 2A unless otherwise
• Nipple Inversion/Retraction without Palpable Mass (BSCR-8) indicated.
• Nipple Discharge, No Palpable Symptom (BSCR-9)
See NCCN Categories of Evidence
• Skin Changes (BSCR-10) and Consensus.
• Persistent or Severe Breast Pain (BSCR-11)
• Axillary Mass (BSCR-13)
Presentation of Symptoms in Individuals Assigned Male at Birth (BSCR-14)
Mammographic or Ultrasound Evaluation and Follow-up (BSCR-18)
Breast Screening Considerations (BSCR-A)
Recommendations for Breast Cancer Screening and Evaluation During Pregnancy and Lactation (BSCR-B)
Breast Imaging Assessment Category Definitions (BSCR-C)
Abbreviations (ABBR-1)
The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to
treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual
clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations
or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN
Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may
not be reproduced in any form without the express written permission of NCCN. ©2023.

Table of Contents
Terminologies in all NCCN Guidelines are being actively modified to advance the goals of equity, inclusion, and representation.
Updates in Version 1.2023 of the NCCN Guidelines for Breast Cancer Screening and Diagnosis from Version 1.2022 include:
Global Updates Footnotes
• All instances of screening or diagnostic mammography within the algorithm • p, New: Consider mammogram beginning at age 25 y on a case by case basis
(excluding footnotes) have been modified to include with tomosynthesis depending on family history.
• All instances of MRI within the algorithm (excluding footnotes) have been • r, New: Many experts recommend alternating the mammogram and breast MRI
modified to include with and without contrast with and without contrast every 6 months. While there is limited data to support
BSCR-1 this approach, the presumption is that this may lead to earlier identification of
Average Risk Age ≥40 y: cancer. (Also for BSCR-3, BSCR-4).
• Deleted: Tomosynthesis is recommended, if available. (Also for BSCR-2, BSCR- BSCR-5
3, BSCR-4). • Column 2, row 2, New: Acquired/new onset nipple inversion/retraction, with or
• Bullet 4, New: Consider supplemental screening for those with heterogeneous or without palpable mass.
extremely dense breasts (BSCR-A). (Also for BSCR-4). Bottom pathway, modified:
Footnotes ◊ Bullet 1: Breast implant associated anaplastic large cell lymphoma (BIA-
• h, modified: Risk models that are largely dependent on family history (eg, Claus, ALCL) (effusion, enlargement, mass)
BRCAPRO, Tyrer-Cuzick, BOADICEA/CanRisk). See NCCN Guidelines for ◊ Bullet 2: Breast implant associated squamous cell carcinoma (BIA-SCC)
Breast Cancer Risk Reduction. There are significant limitations in interpretation (ulceration)
of polygenic risk scores (PRS). PRS should not be used for clinical management Diagnostic evaluation
at this time and use is recommended in the context of a clinical trial, ideally • Row 6, modified: Pain evaluation, (See BSCR-11)
including diverse populations. See NCCN Guidelines for Genetic/Familial High- • Bottom pathway, modified:
Risk Assessment: Breast, Ovarian, and Pancreatic. (Also for BSCR-2). Bullet 1: Consultation with multidisciplinary team with experience in managing
• k, modified: Rationale for recommending clinical encounter is to maximize earliest BIA-ALCL and BIA-SCC with implant-related problems including BIA-ALCL
detection of breast cancers and assure ongoing risk assessment, particularly in Bullet 2: For diagnostic workup of BIA-ALCL, also See NCCN Guidelines for
regions where mammographic screening may not be accessible. Randomized T-Cell Lymphomas
trials comparing incremental CBE versus no mammographic screening have not Footnotes
been performed. (Also for BSCR-2, BSCR-3, BSCR-4). • v, modified: Including mass, new onset asymmetric thickening/nodularity,
BSCR-2 asymmetric breast enlargement, or change in shape/contour.
Screening/Follow-Up: • w, modified: Individuals with breast implants have a very small risk of developing
• Consider contrast-enhanced mammography (CEM) or molecular breast imaging BIA-ALCL (average 7–9 years after implantation) and BIA-SCC. The majority
(MBI) whole breast ultrasound for those who qualify for but cannot undergo MRI. of cases of BIA-ALCL have been seen in textured implants, while BIA-SCC is
Whole breast ultrasound may be done if contrast-enhanced imaging or functional associated with either smooth or textured implants. Only symptomatic individuals
imaging is not available/accessible. (Also for BSCR-3, BSCR-4). need to be evaluated.
Continued
Version 1.2023 , 06/19/23 © 2023 National Comprehensive Cancer Network (NCCN ), All rights reserved. NCCN Guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
® ® ®
UPDATES

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BSCR-6 Normal clinical and or MRI imaging findings
• Column 3, bottom pathway, modified: If low clinical suspicion: Consider observing • Deleted following pathway: Biopsy of skin or nipple, Benign/Malignant, Approprite
for 1-2 menstrual cycles clinical management, See NCCN Guidelines for Breast cancer.
• Column 4, top pathway, modified: Diagnostic mammogram with tomosynthesis or Footnotes
CEM if available + ultrasound • Deleted: This may include a referral to a breast specialist, supplemental imaging,
• Column 5, bullet 2, modified to include, of malignancy and tissue sampling.
Footnotes BSCR-13
• x, New: CEM may be considered if available when clinically suspicious. (Also for Footnotes
BSCR-10, BSCR-13). • eee, modified: ... Assess recent COVID-19 vaccination status and manage
• y, modified: ...CBE to be documented, as clock/quadrant location and distance.. accordingly.
BSCR-7 • iii, modified: If lymphoma is suspected, it tissue/specimen may require special
• This page has been significantly updated. pathologic processing and/or surgical excision.
BSCR-8 BSCR-14
• New page: Management of Nipple Inversion/Retraction Footnotes
BSCR-9 • kkk, New: Mammogram generally not performed prior to age 25 y for individuals
• Column 6, MRI added to BI-RADS 1-3 and BI-RADS 4-5 AMAB.
• Column 7, modified: 6-mo follow-up physical examination ± imaging diagnostic • lll, New: Clinical management depends on the presumed cause (drug-induced,
mammogram ± ultrasound for 1-2 y hypogonadism, hyperthyroidism, idiopathic), age of patient, duration, and
Footnotes presence of symptoms.
• ff, New: Patients should have clinical follow up and/or be instructed to monitor for BSCR-15
and report any changes. • This page has been significantly updated.
• nn, New: Nipple smear cytology is rarely helpful and NOT recommended. BSCR-16
BSCR-10 • Pleomorphic Non-Classic LCIS.
• Column 2, bottom pathway, modified: ...Paget disease or other manifestations of Footnotes
breast cancer includes but is not limited to: • ppp, modified: Clinicians should consider complete excision with negative
• Column 5, deleted: Reassess clinical suspicion margins for pleomorphic non-classic LCIS, florid LCIS, and multifocal/extensive
• Column 6, modified: LCIS involving >4 terminal ductal lobular units on a core biopsy.
Abnormal clinical and/or MRI imaging findings
Continued
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UPDATES

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BSCR-A, 1 of 2 Footnotes
• This page has been significantly updated. • Deleted: Abnormal nipple discharge includes bloody or clear, uniductal, unilateral
BSCR-A, 2 of 2 discharge. Milky discharge is generally normal in pregnancy.
• Bullet 1, modified: For individuals with a genetic mutation, or a an untested first- (Also for BSCR-B, 8)
degree relative of gene mutation carrier, see ... BSCR-B, 4 of 11
Footnotes • Column 1, top pathway, modified: Breast Erythema or Suspicious Worrisome Skin
• a, modified: For age ˃75 years, supplemental screening recommendations are Changes...
considered on an individual basis. BSCR-B, 5 of 11
• Deleted: Risk depends on age at diagnosis. • Bottom pathway, New: Management of Axillary Mass
BSCR-B, 1 of 11 BSCR-B, 8 of 11:
Increased Risk Screening Rational for Recommendation/Other Considerations
• Column 1, Bullet 1, modified: Individuals with a genetic mutation, or a first-degree • Column 6, Bullet 4, modified: While there is a small theoretical concern of milk
relative of gene mutation carrier who remains untested. (Also for BSCR-B, 6) fistula with core needle biopsy, biopsy should proceed in the usual prompt
Rational for Recommendation/Other Considerations timeframe following a BI-RADS 4 or BI-RADS 5 imaging result during lactation.
• Bullet 3, modified to include: Non-contrast MRI is not recommended due to lack of pregnancy
sensitivity. BSCR-B, 9 of 11
Footnotes • Column 1, modified: Breast Erythema or Suspicious Worrisome Skin Changes
• a, New: There are significant limitations in interpretation of PRS. PRS should (eg, thickening or edema)
not be used for clinical management at this time and use is recommended in the Rational for Recommendation/Other Considerations
context of a clinical trial, ideally including diverse populations.(Also for BSCR-B, • Column 6, Bullet 1, modified: Breast erythema or suspicious worrisome skin
6) changes may be due to puerperal mastitis and all patients should undergo
• c, New: Consider supplemental screening for those with heterogeneous or evaluation and, if clinically consistent with mastitis, appropriate treatment should
extremely dense breasts. (Also for BSCR-B, 6) proceed, including the use of antimicrobials.
BSCR-B, 2 of 11 Bullet 2, modified: In some circumstances, breast erythema or suspicious
Rational for Recommendation/Other Considerations worrisome skin changes without other evidence of mastitis (absence of pain or
• Column 6, Bullet 4, modified: Breast MRI is not appropriate for the management fever) may prompt immediate evaluation for inflammatory breast cancer.
of palpable symptom during pregnancy. Contrast-enhanced breast MRI is Bullet 3, sub-bullet 1, modified: Breast imaging is nearly always indicated to
not recommended during pregnancy due to the trans-placental passage of assist in the diagnosis of persistent breast erythema or skin changes that
gadolinium, and potential concerns of exposure of gadolinium to the fetus. Non- have failed usual treatment for mastitis. In this circumstance, age-appropriate
contrast MRI is not recommended due to lack of sensitivity. Also for BSCR-B, 3, evaluation should proceed similar to individuals who are not lactating pregnant
BSCR-B, 4 (BSCR-10).
BSCR-B, 3 of 11 BSCR-B, 11 of 11
Rational for Recommendation/Other Considerations • Column 5, Under MRI, Not recommended, New: Recommended if MRI was the
• Column 6, Bullet 1 modified: Because of the frequency of normal nipple imaging modality that initially resulted in the BI-RADS 3 finding and there are no
discharge during pregnancy, abnormal nipple discharge is defined as: Persistent, ultrasound or mammographic correlates.
spontaneous uni-ductal, unilateral bloody or clear nipple discharge. (Also for BSCR-B 12 through BSCR-B, 14
BSCR-B, 8) • These pages have been deleted.
Continued
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UPDATES

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SCREENING OR SYMPTOM CATEGORYa SCREENING/FOLLOW-UPb
• Clinical encounterb,d,k every 1–3 y

Age ≥25 but <40 y • Breast awarenessl
Average • Annual clinical encounterb,d,k

risk • Annual screeningb mammogramc,m,n
with tomosynthesiso (category 1)
Age ≥40 y • Breast awarenessl
• Consider supplemental screening for those
with heterogeneous or extremely dense breasts
(BSCR-A)
• Residual lifetime risk ≥20% as defined
by models that are largely dependent Increased Risk Screening Follow-up (BSCR-2)
on family historyg,h,i
Asymptomatic
• Thoracic radiation therapy (RT) between Increased Risk Screening Follow-up (BSCR-3)
ages 10 and 30 y
• 5-year risk of invasive breast cancer
Clinical encounter ≥1.7% in individuals ≥35 yi (per Gail
including risk Model)
Increased
assessmentb,c,d,e,f • Atypical ductal hyperplasia [ADH] and Increased Risk Screening Follow-up (BSCR-4)
Refer to the NCCN risk ≥20% residual lifetime risk
Guidelines for • Lobular neoplasia (lobular carcinoma in
Breast Cancer Risk situ [LCIS]/atypical lobular hyperplasia
Reduction for a [ALH]) and ≥20% residual lifetime risk
detailed qualitative
and quantitative • Pedigree suggestive of/or known
risk assessment. genetic predispositionh,j Increased Risk Screening Follow-up (See NCCN
�Refer to a genetic counselor or other Guidelines for Genetic/Familial High-Risk
health professional with expertise Assessment: Breast, Ovarian, and Pancreatic)
and experience in cancer genetics
Symptomatic Presenting Signs/Symptoms (BSCR-5)
Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
BSCR-1

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FOOTNOTES
a For individuals with a prior history of breast cancer, please refer to the NCCN Guidelines for Breast Cancer - Surveillance Section.
b Breast Screening Considerations (BSCR-A).
c Medicare and insurers allow the individual direct access to scheduling for screening mammography.
d At minimum, medical and family history should be reviewed and clinical encounter should encompass ongoing risk assessment, risk reduction counseling, and
preferably a clinical breast examination (CBE) even in individuals who are asymptomatic when feasible.
e There is limited data on screening in individuals with increased risk for breast cancer assigned male at birth (AMAB).
f For pregnant and lactating individuals, see BSCR-B.
g Individuals with a residual lifetime risk of 15%–20% may be considered for supplemental screening on an individual basis, depending on risk factors.
h Risk models that are largely dependent on family history (eg, BRCAPRO, Tyrer-Cuzick, BOADICEA/CanRisk). See NCCN Guidelines for Breast Cancer Risk
Reduction. There are significant limitations in interpretation of polygenic risk scores (PRS). PRS should not be used for clinical management at this time and use is
recommended in the context of a clinical trial, ideally including diverse populations. See NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian,
and Pancreatic.
i See Comparison of Predictive Models for Risk Assessment (NCCN Guidelines for Breast Cancer Risk Reduction).
j There is variation in recommendations for initiation of screening for different genetic syndromes. See NCCN Guidelines for Genetic/Familial High-Risk Assessment:
Breast, Ovarian, and Pancreatic.
k Rationale for recommending clinical encounter is to maximize earliest detection of breast cancers and assure ongoing risk assessment, particularly in regions where
mammographic screening may not be accessible. Randomized trials comparing incremental CBE versus mammographic screening have not been performed.
l Individuals should be familiar with their breasts and promptly report changes to their health care provider. See Symptomatic During Clinical Encounter, Presenting Signs
and Symptoms (BSCR-5).
m Mammographic Evaluation (BSCR-18).
n Shared decision-making is encouraged based on individuals' values and preferences.
o Tomosynthesis can decrease call back rates and improve cancer detection compared with 2D mammography alone.

BSCR-1A

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SCREENING OR SYMPTOM CATEGORYa SCREENING/FOLLOW-UP
Increased Risk: • Clinical encounterb,d,k every 6–12 mo

To begin when identified as being at increased risk, but not prior to age 21 y
�Consider referral to a genetic counselor or other health professional with expertise and experience in
cancer genetics, if not already done
Consider referral to a breast specialist as appropriate
• Annual screeningb mammogramc,m with tomosynthesiso
Residual lifetime risk ≥20% as defined To begin 10 years prior to when the youngest family member was diagnosed with breast cancer, not
prior to age 30 yp or begin at age 40 y (whichever comes first)
by models that are largely dependent
• Annual breast MRIq,r with and without contrast
on family historyg,h,i Consider contrast-enhanced mammography (CEM)b or molecular breast imaging (MBI)b for those
who qualify for but cannot undergo MRI. Whole breast ultrasoundb may be done if contrast-enhanced
imaging or functional imaging is not available/accessible
To begin 10 years prior to when the youngest family member was diagnosed with breast cancer, not
prior to age 25 ys or begin at age 40 y (whichever comes first)
• Consider risk reduction strategies (See NCCN Guidelines for Breast Cancer Risk Reduction)
• Breast awarenessl
a For individuals with a prior history of breast cancer, please refer to the NCCN k Rationale for recommending clinical encounter is to maximize earliest detection
Guidelines for Breast Cancer - Surveillance Section. of breast cancers and assure ongoing risk assessment, particularly in regions
b Breast Screening Considerations (BSCR-A). where mammographic screening may not be accessible. Randomized trials
c Medicare and insurers allow the individual direct access to scheduling for comparing incremental CBE versus mammographic screening have not been
screening mammography. performed.
d At minimum, medical and family history should be reviewed and clinical l Individuals should be familiar with their breasts and promptly report changes
encounter should encompass ongoing risk assessment, risk reduction to their health care provider. See Symptomatic During Clinical Encounter,
counseling, and preferably a CBE even in individuals who are asymptomatic Presenting Signs and Symptoms (BSCR-5).
when feasible. m Mammographic Evaluation (BSCR-18).
g Individuals with a residual lifetime risk of 15%–20% may be considered for o Tomosynthesis can decrease call back rates and improve cancer detection
supplemental screening on an individual basis, depending on risk factors. compared with 2D mammography alone.
h Risk models that are largely dependent on family history (eg, BRCAPRO, Tyrer- p Consider mammogram beginning at age 25 y on a case by case basis depending
Cuzick, BOADICEA/CanRisk). See NCCN Guidelines for Breast Cancer Risk on family history.
Reduction. There are significant limitations in interpretation of PRS. PRS should q High-quality breast MRI requires a dedicated breast coil, access to biopsy under
not be used for clinical management at this time and use is recommended in MRI guidance, experienced radiologists in breast MRI, and regional availability.
the context of a clinical trial, ideally including diverse populations. See NCCN MRI should be correlated with other breast imaging modalities.
r Many experts recommend alternating the mammogram and breast MRI with
Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and
Pancreatic. and without contrast every 6 months. While there is limited data to support this
i See Comparison of Predictive Models for Risk Assessment (NCCN Guidelines for approach, the presumption is that this may lead to earlier identification of cancer.
Breast Cancer Risk Reduction). s Except in rare circumstances of a family history of very early-onset breast
cancers before age 30 years.

BSCR-2

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SCREENING OR SYMPTOM CATEGORYa SCREENING/FOLLOW-UP
Increased Risk:
• Annual clinical encounterb,d,k

Current age <25 y Beginning 8 y after RT
Thoracic RT
between ages 10 • Clinical encounterb,d,k every 6–12 mo
and 30 y Begin 8 y after RT
Begin 8 y after RT but not prior to age 25 y
• Annual breast MRIq,r with and without contrast
Current age ≥25 y Consider CEMb or MBIb for those who qualify for but cannot undergo MRI. Whole breast ultrasoundb
may be done if contrast-enhanced imaging or functional imaging is not available/accessible
Begin 8 y after RT but not prior to age 25 y
a For individuals with a prior history of breast cancer, please refer to the NCCN Guidelines for Breast Cancer - Surveillance Section.
c Medicare and insurers allow the individual direct access to scheduling for screening mammography.
d At minimum, medical and family history should be reviewed and clinical encounter should encompass ongoing risk assessment, risk reduction counseling, and
preferably a CBE even in individuals who are asymptomatic when feasible.
k Rationale for recommending clinical encounter is to maximize earliest detection of breast cancers and assure ongoing risk assessment, particularly in regions where
mammographic screening may not be accessible. Randomized trials comparing incremental CBE versus mammographic screening have not been performed.
l Individuals should be familiar with their breasts and promptly report changes to their health care provider. See Symptomatic During Clinical Encounter, Presenting Signs
and Symptoms (BSCR-5).
m Mammographic Evaluation (BSCR-18).
qHigh-quality breast MRI requires a dedicated breast coil, access to biopsy under MRI guidance, experienced radiologists in breast MRI, and regional availability. MRI
should be correlated with other breast imaging modalities.
r Many experts recommend alternating the mammogram and breast MRI with and without contrast every 6 months. While there is limited data to support this approach,
the presumption is that this may lead to earlier identification of cancer.

BSCR-3

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SCREENING OR SYMPTOM SCREENING/FOLLOW-UP

CATEGORYa
Increased Risk:
• Clinical encounterb,d,k every 6–12 mo
To begin when identified as being at increased risk by Gail Model
5-year risk of invasive breast cancer • Annual screeningb mammogramc,m with tomosynthesiso
≥1.7% in individuals ≥35 y (per Gail To begin when identified as being at increased risk by Gail Model
Model)i • Consider risk reduction strategies (See NCCN Guidelines for Breast Cancer Risk Reduction)
• Consider supplemental screening for those with heterogeneous or extremely dense breasts (BSCR-A)
• Clinical encounterb,d,k every 6–12 mo

To begin at diagnosis of ADH or lobular neoplasia (LCIS/ALH)
To begin at diagnosis of ADH or lobular neoplasia (LCIS/ALH) but not prior to age 30 y
ADHt or Lobular neoplasia
• Consider annual breast MRIb,q,r with and without contrast
(LCIS/ALH) and ≥20% residual
Consider CEMb or MBIb for those who qualify for but cannot undergo MRI. Whole breast ultrasoundb may
lifetime risk be done if contrast-enhanced imaging or functional imaging is not available
To begin at diagnosis of ADH or lobular neoplasia (LCIS/ALH) but not prior to age 25 y
a For individuals with a prior history of breast cancer, please refer to the NCCN
Guidelines for Breast Cancer - Surveillance Section.
c Medicare and insurers allow the individual direct access to scheduling for l Individuals should be familiar with their breasts and promptly report changes
screening mammography. to their health care provider. See Symptomatic During Clinical Encounter,
d At minimum, medical and family history should be reviewed and clinical Presenting Signs and Symptoms (BSCR-5).
encounter should encompass ongoing risk assessment, risk reduction m Mammographic Evaluation (BSCR-18).
counseling, and preferably a CBE even in individuals who are asymptomatic o Tomosynthesis can decrease call back rates and improve cancer detection
when feasible. compared with 2D mammography alone.
i See Comparison of Predictive Models for Risk Assessment (NCCN Guidelines for q High-quality breast MRI requires a dedicated breast coil, the access to biopsy
Breast Cancer Risk Reduction). under MRI guidance, experienced radiologists in breast MRI, and regional
k Rationale for recommending clinical encounter is to maximize earliest detection availability. MRI should be correlated with other breast imaging modalities.
of breast cancers and assure ongoing risk assessment, particularly in regions r Many experts recommend alternating the mammogram and breast MRI with
where mammographic screening may not be accessible. Randomized trials and without contrast every 6 months. While there is limited data to support this
comparing incremental CBE versus mammographic screening have not been approach, the presumption is that this may lead to earlier identification of cancer.
performed. t Risk depends on age at diagnosis.

BSCR-4

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PRESENTING SIGNS/SYMPTOMS DIAGNOSTIC

EVALUATION
Age ≥30 y (See BSCR-6)
Palpable
symptomv
Age <30 y (See BSCR-6)
Acquired/new onset nipple

inversion/retraction, with or (See BSCR-8)
without palpable mass
Nipple discharge,
no palpable (See BSCR-9)
symptom
Skin changes:
Symptomatic during • Peau d’orange
clinical encounteru • Erythema (See BSCR-10)
• Nipple excoriation
• Scaling, eczema
• Skin ulcers
Breast pain (See BSCR-11)
Axillary mass(es) (See BSCR-13)

Breast implant-related symptomsw >1 y
post-implantation: • Consultation with multidisciplinary team
• Breast implant associated anaplastic with experience in managing BIA-ALCL
large cell lymphoma (BIA-ALCL) and BIA-SCCw
(effusion, enlargement, mass) • For BIA-ALCL, also See NCCN Guidelines
or for T-Cell Lymphomas
• Breast implant associated squamous cell
carcinoma (BIA-SCC) (ulceration)
w Individualswith breast implants have a very small risk of developing BIA-ALCL

u For symptoms in individuals AMAB, see BSCR-14.
(average 7–9 years after implantation) and BIA-SCC. The majority of cases of
v Including mass, new onset asymmetric thickening/nodularity, asymmetric breast BIA-ALCL have been seen in textured implants, while BIA-SCC is associated with
enlargement, or change in shape/contour. either smooth or textured implants.

BSCR-5

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PRESENTING DIAGNOSTIC IMAGING FINDINGS FOLLOW-UP

SIGNS/SYMPTOMS EVALUATION (Highest Imaging Category
by Mammogram and/or Ultrasound)
• BI-RADS category 1 (negative)

Diagnostic • BI-RADS category 2 (benign) See BSCR-7
mammogramx,z • BI-RADS category 3 (probably benign)
with tomosynthesiso
Age ≥30 y or
CEMx,z if available +
ultrasoundaa
• BI-RADS category 4 (suspicious) Core needle
Palpable or biopsycc
If clinically Ultrasound preferredbb • BI-RADS category 5 (highly suggestive
symptomv,y (BSCR-15)
suspicious of malignancy)
Age <30 y
Symptom persists
If low clinical
suspicion:
Consider
observing for 1–2
Screening
menstrual cycles Symptom resolves (BSCR-1)
z There are some clinical circumstances such as mass with low clinical suspicion
o Tomosynthesis can decrease call back rates and improve cancer detection or suspected simple cyst in which ultrasound would be preferred as the first
compared with 2D mammography alone. imaging modality and may suffice for individuals aged 30–39 years. Mammogram
v Including mass, new onset of asymmetric thickening/nodularity, asymmetric may not be necessary if performed and results were negative within the past 6
breast enlargement or change in shape/contour. months. See Discussion.
x CEM may be considered if available when clinically suspicious. aa Ultrasound may not be necessary for a palpable finding with a definitively
y It is critical for the location of physical findings from CBE to be documented, benign finding (eg, calcified fat necrosis) on mammogram.
as clock/quadrant location and distance from nipple to facilitate geographic bb If high suspicion for malignancy, obtain mammogram.
correlation with imaging findings. cc Confirm geographic correlation between clinical and imaging findings.

BSCR-6

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IMAGING FINDINGS WITH PALPABLE SYMPTOMv,y FOLLOW-UP

AFTER IMAGING
If clinically suspicious
BI-RADS Palpable Symptom
category 1dd,ee Significant increase in (BSCR-6)
(negative) size or clinical suspicion
If low clinical suspicion:
Physical examination at 3-6 moff
Stable or decrease in size
Screeninggg
If low clinical suspicionff: (BSCR-1)
BI-RADS (eg, simple cyst)
category 2dd,ee Palpation-guided tissue
(benign) sampling (by core needle
If clinically suspicious: biopsy BSCR-15, fine needle
aspiration [FNA] BSCR-17 or
excision BSCR-16)
If low clinical suspicionff: Stable or Screeninggg

Physical examination + imaging decrease in size (BSCR-1)
(ultrasound or diagnostic
BI-RADS mammogram with tomosynthesis)o
category 3dd for up to 24 mohh to assess Significant increase in size
(probably benign) for changes or clinical suspicion Core needle biopsyee,ii
(BSCR-15)
If clinically suspicious
ee Aspiration may be considered for symptomatic relief or possible abscess.

o Tomosynthesis can decrease call back rates and improve cancer detection (BSCR-17).
compared with 2D mammography alone. ff Patients should have clinical follow up and/or be instructed to monitor for and
v Including mass, new onset of asymmetric thickening/nodularity, asymmetric report any changes.
breast enlargement or change in shape/contour. gg Continue regular screening with age-appropriate imaging modality.
y It is critical for the location of physical findings from CBEs to be documented, hh Imaging modality would depend on original imaging. Probably benign findings
as clock/quadrant location and distance from nipple to facilitate geographic are typically monitored at 6, 12, and 24 months.
correlation with imaging findings. ii Core needle biopsy preferred; in some circumstances needle aspiration may be
dd Assessment Category Definitions (BSCR-C). sufficient.

BSCR-7

Table of Contents
MANAGEMENT OF NIPPLE INVERSION/RETRACTION

PRESENTING DIAGNOSTIC IMAGING FINDINGS FOLLOW-UP
SIGNS/SYMPTOMS EVALUATION BI-RADS Low clinical
category 1 suspicionff Screening (BSCR-1)gg
(negative)
or
BI-RADS Abnormal
Clinically Core
category 2 • Consider referral clinical
suspicious needle
(benign) to breast and/or MRI
specialist imaging biopsy
findings (BSCR-15)
• Consider
Perform CBE with breast Normal
Breast imaging MRI with and clinical
attention to:
• Age ˂30 y: Clinically Screeninggg
• Presence of mass without and MRI (BSCR-1)
breast suspicious
underneath nipplejj contrast imaging
ultrasound BI-RADS findings
Acquired/ • Presence of nipple • Age ≥30 y: category 3
new-onset discharge and color diagnostic (probably • Physical examination at
of nipple • Evidence of Mammo-
mammogram benign) 6-months ± diagnostic
Nipple retraction inflammation graphic
with mammogram with
(erythema, fistula Low clinical and/or
inversion/ tomosynthesiso tomosynthesiso ±
retraction on areola or nipple, suspicionff Ultrasound
and breast ultrasound for 1–2 yff,hh Evaluation
without purulent discharge,
ultrasound • Consider referral to (BSCR-18)
palpable tenderness)
breast specialist
mass
Congenital/ If recent changes

life long • Core needle biopsy (BSCR-15)
nipple • Reassurance BI-RADS 4
inversion • Screeninggg or • Surgical excision if not
No recent changesff amenable to core needle
(BSCR-1) BI-RADS 5
biopsy (BSCR-16)
o Tomosynthesis can decrease call back rates and improve cancer detection hh Imaging modality would depend on original imaging. Probably benign findings
compared with 2D mammography alone. are typically monitored at 6, 12, and 24 months.
ff Patients should have clinical follow up and/or be instructed to monitor for and jj For palpable mass see BSCR-6.
report any changes.
gg Continue regular screening with age-appropriate imaging modality.

BSCR-8

Table of Contents
PRESENTING DIAGNOSTIC EVALUATION AND FOLLOW-UP FOLLOW-UP

SIGNS/SYMPTOMS AFTER IMAGING
• Observation
Age <40 y
• Educate to stop compression of the breast and report any spontaneous discharge
Non-spontaneous
or • Screening mammogram with tomosynthesiso if not Mammographic
multi-duct Age ≥40 y done in the past year evaluation
• Educate to stop compression of the breast and report (BSCR-18)
any spontaneous discharge Core needle
Suspicious biopsy if imaging
6-mo follow- progression abnormality
up physical (BSCR-15)
examination ± or
Nipple imaging for Surgical excision
dischargekk,ll • MRI with 1–2 yff,hh (BSCR-16)
no palpable Age <30 y and without MRI BI-RADS Stable/
symptommm,nn ultrasound ± contrast
BI-RADS category 1–3 resolves Screeninggg
diagnostic category • Refer to
mammogram Surgical (BSCR-1)
1–3dd,oo breast Benign
with specialist consultation
MRI BI-RADS
tomosynthesiso for duct
category 4–5
Persistent and excisionpp
reproducible on See NCCN
examination, Malignant Guidelines for
spontaneous, Breast Cancer
unilateral, single Age ≥30 y
duct, and clear diagnostic BI-RADS Core needle biopsy (BSCR-17);
or bloody mammogram category surgical excision (BSCR-16) if not
with 4–5dd amenable to core needle biopsy Consider surgical
tomosynthesiso Benign
consultation for
+ ultrasound duct excisionpp
o Tomosynthesis kk A list of drugs that can cause nipple discharge (not all-inclusive): psychoactive
can decrease call back rates and improve cancer detection
compared with 2D mammography alone. drugs, antihypertensive medications, opiates, oral contraceptives, and estrogen.
dd Assessment Category Definitions (BSCR-C). ll For bilateral milky discharge consider endocrine workup.
ff Patients should have clinical follow up and/or be instructed to monitor for and mm If palpable symptom, see BSCR-6.
nn Nipple smear cytology is rarely helpful and NOT recommended.
report any changes.
hh Imaging modality would depend on original imaging. Probably benign findings oo If BI-RADS category 3 finding is unrelated to nipple discharge, manage
are typically monitored at 6, 12, and 24 months. mammographic finding by BSCR-18.
pp Based on clinical suspicion and patient preference.

BSCR-9

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PRESENTING SIGNS/SYMPTOMS DIAGNOSTIC EVALUATION AND FOLLOW-UP
• Consider Abnormal
BI-RADS Core needle biopsy
referral to clinical and/or
category 1–3dd (preferred) ± biopsy of
breast MRI imaging
(negative, skin or nippleuu
specialist findings
Suspicion for possible benign, • Consider
inflammatory breast or breast MRI
cancerx,qq includes but probably with and Normal
is not limited to: benign without clinical and Screening
• Peau d’orange findings) contrast MRI imaging (BSCR-1)
(pitted or dimpled findings
appearance of skin)
• Skin thickening
• Edema Diagnostic
• Erythema mammogram
Skin
changesrr,ss with
tomosynthesiso
Suspicion for possible ± ultrasoundx
Paget disease or other • Consider surgical referral
manifestations • Consider biopsy of skin or
of breast cancer Benigntt nipple (see pathway above)
includes but is not BI-RADS • Consider MRI with and
limited to: category 4–5dd without contrast
• Nipple excoriation Core needle
(suspicious or biopsy
• Scaling highly
• Skin ulceration (preferred)
suggestive of
malignancy) See NCCN Guidelines
Malignant
for Breast Cancer
x CEM may be considered if available when clinically suspicious.
dd Assessment Category Definitions (BSCR-C).
qq This may represent serious disease of the breast and needs evaluation.
rr If clinically low suspicion for breast cancer or high suspicion for infection, a short trial (eg, 7–10 days) of antibiotics for mastitis may be indicated.
ss If clinically low suspicion for Paget's disease or high suspicion for eczema, a short trial of topical steroids may be indicated.
tt A benign skin punch biopsy in a patient with a clinical suspicion of inflammatory breast cancer does not rule out malignancy. Further evaluation is recommended.
uu Inflammatory breast cancer is a clinical diagnosis and is not dependent on a positive punch biopsy.

BSCR-10

Table of Contents
PRESENTING SIGNS AND SYMPTOMS FOLLOW-UP EVALUATION
Palpable symptoms See BSCR-6
Nipple
See BSCR-9
discharge
Persistent Complete
or severe history and
breast painvv physical
Skin
See BSCR-10
changes
Cyclic, diffuse,
non-focal pain • Reassuranceww
(larger than • Treatment if needed/desired
No physical quadrant)ww
findings Ultrasound +
≥30 y mammogramxx
with
Focal tomosynthesiso (See BSCR-12)
pain
<30 y Ultrasoundbb
bb If high suspicion for malignancy, obtain mammogram.
vv Defined as a minimum of 4 to 6 weeks duration; prior to that, symptomatic
management unless patient reports other symptoms also present such as associated
redness or mass. If other symptoms present, physical examination should be done at that time.
ww Ensure that mammographic screening is up-to-date.
xx There are some clinical circumstances such as a suspected painful simple cyst in which ultrasound would be preferred as the first imaging modality and may suffice
for individuals aged 30–39 years. Mammogram may not be necessary if performed and results were negative within the past 6 months. See Discussion.

BSCR-11

Table of Contents
IMAGING FINDINGS FOR FOCAL BREAST PAIN FOLLOW-UP EVALUATION
BI-RADS Symptomatic management

category 1dd (See Discussion)
Screening
If simple cyst, consider (BSCR-1)
BI-RADS
drainage for symptom
category 2dd
relief aaa
Stable
Physical examination +
imaging (ultrasound or
BI-RADS diagnostic mammogram)
category 3dd,zz with tomosynthesiso for
up to 24 mohh,yyto assess Significant
for changes increase in
size or
BI-RADS suspicion
category 4dd,zz Core needle biopsy
(BSCR-15)
BI-RADS
category 5dd
hh Imaging modality would depend on original imaging. Probably benign findings are typically monitored at 6, 12, and 24 months.
yy There may be variability on the follow-up interval of physical examination based on the level of suspicion.
zz When imaging indicates possible abscess as cause of focal pain, consider aspiration or surgical consultation.
aaa If complicated cyst, consider aspiration.

BSCR-12

Table of Contents
RECOMMENDATIONS FOR WORKUP/DIAGNOSTIC EVALUATION OF AXILLARY MASS

PRESENTATION EVALUATION
Appropriate clinical managementbbb
Systemic or
diseaseeee See NCCN Guidelines for appropriate malignancy, if malignant
Bilateral Clinical
evaluationddd Negative/ Appropriate
Diagnostic benignfff clinical
No
mammogramfff,ggg,hhh If benign managementbbb
systemic
with tomosynthesiso
disease
+ ultrasoundfff Suspicious Malignant axillary Breast MRI
lymph node
Axillary (breast origin)
mass(es) and
and
expected to no breast mass
represent Tissue
adenopathyccc samplingiii Malignant axillary See NCCN
lymph node and Guidelines for
breast cancer Breast Cancer
Suspicious
See NCCN
Diagnostic
Guidelines for
mammogrameee,fff,ggg,hhh Malignant axillary
Unilateral appropriate
with tomosynthesiso lymph node (non- malignancy, if
+ ultrasoundx,fff breast origin) malignant
o Tomosynthesis can decrease call back rates and improve cancer detection compared with 2D Appropriate
mammography alone. Negative/ clinical
x CEM may be considered if available when clinically suspicious. benignfff managementbbb
bbb This may include a referral to a breast specialist, supplemental imaging, and tissue
fff For additional guidance based upon BI-RADS category 3 (probably
sampling.
ccc If not expected to represent adenopathy, see BSCR-5. benign) assessment, see BSCR-18.
ddd Complete clinical evaluation to assess for other sites of adenopathy and potential non-breast ggg If aged <30 years, mammogram is optional unless ultrasound
etiologies of adenopathy. results are suspicious.

eee Evidence of clinical conditions known to be associated with systemic adenopathy such as hhh Mammogram is recommended in those ≥30 years.
iii If lymphoma is suspected, tissue/specimen may require special
lupus, rheumatoid arthritis, human immunodeficiency virus (HIV) infection, and others. Assess
recent vaccination status and manage accordingly. pathologic processing and/or surgical excision.

BSCR-13

Table of Contents
PRESENTATION OF SYMPTOMS IN DIAGNOSTIC EVALUATION FOLLOW-UP

INDIVIDUALS ASSIGNED MALE AT EVALUATION
BIRTH jjj,kkk
Bilateral breast
enlargement Reassurance
consistent with with clinical
gynecomastia or managementlll
pseudogynecomastia
Clinical
BI-RADS category 1–3
managementmmm
Presumed asymmetric Diagnostic mammogramkkk with (negative/benign/
See BSCR-7 if
gynecomastia tomosynthesiso ± ultrasound probably benign)
BIRADS category 3
Palpable symptom
not explained by
gynecomastia
Diagnostic mammogramkkk with
OR tomosynthesiso + ultrasound
BI-RADS category 4-5
(suspicious/highly Core needle biopsy
Bloody nipple (BSCR-15)
suggestive of malignancy)
discharge
jjj See NCCN Guidelines for Breast Cancer for management and special considerations for breast cancer in individuals AMAB.
kkk Mammogram generally not performed prior to age 25 y for individuals AMAB.
lll Clinical management depends on the presumed cause (drug-induced, hypogonadism, hyperthyroidism, idiopathic), age of patient, duration, and presence of
symptoms.
mmm Consider surgical referral for suspicious clinical findings.

BSCR-14

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FOLLOW-UP EVALUATION AFTER CORE NEEDLE BIOPSY

Screening
Screeningsss (BSCR-1) Stable
Benign pathology is (BSCR-1)
or
concordant with imaging Physical examination and/or
findingsnnn imaging at 6 or 12 mo for up to
Significant
1 y to assess for changesyy
Indeterminate increase in
or size or
Benign suspicion
and image Surgical
discordant excision (BSCR-16)
or
ADHooo Discordant
Core or with imaging
needle Non-classic
Screening (BSCR-1)
biopsy LCISppp
or
Physical examination and/or imaging
Pathology is at 6 to 12 mo for up to 1 y to assess
concordant for changes yy
Other specific
with imaging and
histologiesqqq,rrr
findingsnnn,ppp Counseling for risk reduction See
NCCN Guidelines for Breast Cancer
Risk Reduction
See NCCN Guidelines
Malignant
for Breast Cancer
yy There may be variability on the follow-up interval of physical examination based
on the level of suspicion.
nnn Concordance established by radiologist/breast specialist after review of qqq For select patients with other specific histologies (eg, classic LCIS, ALH, flat
core needle biopsy pathology report and imaging findings. This may require epithelial atypia [FEA], papillomas without atypia, fibroepithelial lesions favoring
discussion/review with pathologist. fibroadenoma, radial scars adequately sampled or incidental, ADH) excision may
ooo Select patients may be suitable for monitoring in lieu of surgical excision. be considered depending on level of suspicion.
ppp Clinicians should consider complete excision with negative margins for non- rrr Other histologies that may require additional tissue: mucin-producing lesions,
classic LCIS, florid LCIS, and multifocal/extensive LCIS involving >4 terminal potential phyllodes tumor, papillary lesions, radial scar, or histologies of concern
ductal lobular units on a core biopsy. However, outcomes data regarding to pathologist.
treatment of individuals with non-classic LCIS are limited, due in part to a paucity sss While most would return to annual screening, there is the option of physical
of histologic categorization of variants of LCIS. examination with or without further imaging for individuals ˂40 years.

BSCR-15

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FOLLOW-UP EVALUATION AFTER SURGICAL EXCISION

Benignttt Screening (BSCR-1)
ADH
Screening (BSCR-4) and

Surgical excision See NCCN Guidelines for Breast Cancer
Classic LCIS Risk Reduction
Non-classic LCISppp
Malignant See NCCN Guidelines for Breast Cancer
ppp Clinicians should consider complete excision with negative margins for non-classic LCIS, florid LCIS, and multifocal/extensive LCIS involving >4 terminal ductal
lobular units on a core biopsy. However, outcomes data regarding treatment of individuals with non-classic LCIS are limited, due in part to a paucity of histologic
categorization of variants of LCIS.
ttt Includes lesions such as radial scar, papillomas, and FEA.

BSCR-16

Table of Contents
FOLLOW-UP EVALUATION AFTER ASPIRATION
Ultrasound + image-guided core

Mass persists needle biopsy
(BSCR-15)
Consider core needle biopsy

Negative cytology or
Mass resolves Short-term clinical/imaging follow-up

After but non-traumatic,
aspiration bloody fluid
obtaineduuu
Atypical or malignant Surgical excision
cytologywww (BSCR-16)
Mass resolves and Clinical follow-up + imaging

Screening
non-bloody cyst Mass recurs (BSCR-6)
(BSCR-1)
fluid obtainedvvv
uuu Place marker clip and send to cytology.

vvv Routine cytology is not recommended.
www There are some circumstances in which cytology may be sufficient. If cytology is concordant, core needle biopsy may not be needed.

BSCR-17

Table of Contents
ASSESSMENT CATEGORYdd FOLLOW-UP

Diagnostic workup including
BI-RADS category 0 comparison to prior
(Need additional mammograms and diagnostic See appropriate FINAL
imaging evaluation) mammogram with ASSESSMENT category
tomosynthesiso and/or
ultrasound as indicated
BI-RADS category 1
(Negative) Screening (BSCR-1)
BI-RADS category 2 Screening (BSCR-1)

(Benign finding) Stable or
Imaging (ultrasound or Screening (BSCR-1)
resolving
diagnostic mammogram
Mammographic with tomosynthesis)o for
and/or BI-RADS category 3 up to 24 mohh,yy to assess
ultrasound (Probably benign finding) for changes
evaluation If return visit uncertain or
strong patient preference Core
Increased
may include biopsy needle Follow-up After
BI-RADS category 4 suspicion
biopsy Core Needle Biopsy
(Suspicious abnormality)
After complete imaging evaluation (BSCR-15)
BI-RADS category 5 tissue sampling by image-guided
(Highly suggestive of core needle biopsy
malignancy)
BI-RADS category 6
(Known biopsy - proven See NCCN Guidelines for Breast Cancer
malignancy)
hh Imaging modality would depend on original imaging. Probably benign findings are typically monitored at 6, 12, and 24 months.
yy There may be variability on the follow-up interval of physical examination based on the level of suspicion.

BSCR-18

Table of Contents
BREAST SCREENING CONSIDERATIONS

General Considerations Dense Breasts
• Individuals should undergo breast cancer risk assessment by age 25 years • Dense breasts limit the sensitivity of mammography. Mammographically
and be counseled regarding potential benefits, risks, and limitations of dense breast tissue is associated with an increased risk for breast cancer.
breast screening in the context of their risk stratification. • For individuals with mammographically dense breast tissue
• Shared decision-making is encouraged based on a patient's values and (heterogeneously or extremely dense breast tissue), recommend counseling
preferences (See Discussion). on the risks and benefits of supplemental screening.
• Multiple studies show that tomosynthesis can decrease call back rates and • Handheld or automated ultrasound can increase cancer detection rates in
improve cancer detection compared with 2D mammography alone. Radiation individuals with dense breast tissue, but may increase recall and benign
exposure may be increased, but remain within FDA guidelines and can be breast biopsies.
reduced with FDA-approved synthesized 2D reconstruction.
• Current evidence does not support the routine use of thermography as High Risk Individuals
screening procedures. • In high-risk settings, based on current evidence and considering the FDA
• Due to lack of clinical evidence, these guidelines do not provide screening safety announcement1 (gadolinium-based contrast agents), we continue to
guidance for transgender individuals. Certain organizations have developed recommend annual MRI in select populations after shared decision-making.
consensus-based guidelines for transgender individuals, such as the ACR Breast cancer screening MRI may also increase recall and increase benign
Appropriateness Criteria. NCCN endorses these criteria. Transgender breast biopsies.
individuals should consult with their primary care physician to determine • Abbreviated MRI has a higher cancer detection rate than mammography with
when/whether screening would be appropriate. tomosynthesis and likely has similar sensitivity compared to full diagnostic
protocol breast MRI.
Upper Age Limit for Screening • CEM and MBI are also options for higher risk breast cancer
• Upper age limit for mammographic screening is not yet established. screening. CEM has the risk of iodinated contrast reactions and
• Consider severe comorbid conditions limiting life expectancy (eg, ≤10 years) has a higher breast radiation exposure per exam than standard
and whether therapeutic interventions are planned.
mammography. MBI has a whole-body effective radiation dose
substantially higher than that of mammography.
1 FDA Drug Safety Communication: FDA identifies no harmful effects to date with brain retention of gadolinium-based contrast agents for MRIs; review to continue: https://
www.fda.gov/Drugs/DrugSafety/ucm559007.htm.
Continued
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BREAST SCREENING CONSIDERATIONS

RECOMMENDATIONS FOR BREAST MRI SCREENING AS AN ADJUNCT TO MAMMOGRAPHYa,2
(FOR AGE TO BEGIN SCREENING EXCEPT WHERE NOTED BELOW: SEE BSCR-2)
Recommend Annual MRI Screening:3

• For individuals with a genetic mutation, or an untested first-degree relative of gene mutation carrier, see the NCCN Guidelines for Genetic/
Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic.
• For individuals who received thoracic RT between the ages of 10 and 30 years
• For individuals with a residual lifetime risk ≥20% as defined by models that are largely dependent on family historyb
• Consider annual MRI screening for individuals with ADH or lobular neoplasia (LCIS/ALH) and ≥20% residual lifetime risk
Insufficient Evidence to Recommend for or Against Routine Population-Based MRI Screening:

• Residual lifetime risk 15%–20%, as defined by models that are largely dependent on family history
• Heterogeneously or extremely dense breast on mammography
Recommend Against MRI Screening (Based on Expert Consensus Opinion):

• Individuals at <15% residual lifetime risk
a For age ˃75 years, supplemental screening recommendations are considered on an individual basis.
b Based on the extent of family history, consider referral for genetic testing. Refer to the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian,
and Pancreatic to see whether the patient meets the criteria. If testing is not performed or if negative genetic testing and if residual lifetime risk remains greater than (or
risk still exceeds) 20%, recommend MRI.
2 Adapted with permission from John Wiley and Sons. Copyright ©2007 American Cancer Society. Saslow D, Boetes C, Burke W, et al. American Cancer Society
Guidelines for Breast Cancer Screening with MRI as an Adjunct to Mammography. CA: Cancer J Clin 2007;57:75-89.
3 Individuals with a history of breast cancer with these risk factors should consider supplemental screening.

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MANAGEMENT OF BREAST CANCER SCREENING AND BREAST SYMPTOMS DURING PREGNANCY

Condition Recommendation Rationale for Recommendation/Other Considerations
CBE Mammogram with Ultrasound MRI
Tomosynthesisb
Average Risk Screening in R R NRc NR • There is no contraindication to screening mammography during

Individuals ≥40 Years pregnancy.
• While ionizing radiation exposure with mammography is many-
fold below the threshold of fetal teratogenesis (see comments
below), due to the infrequency of pregnancy-associated breast
cancers (PABC) and the decreased sensitivity and specificity of
mammography during pregnancy, providers and patients may
implement a short delay in routine breast imaging based on prior
imaging and date of delivery in individuals who are at average
risk until after pregnancy.
• There are no data evaluating the use of ultrasound alone as an
alternative screening method in individuals who are at average
risk during pregnancy; therefore, this is not recommended as an
alternative to screening mammography.
Increased Risk Screening R R O NR • In individuals who are at increased risk for breast cancer, it is
• Individuals with a genetic mutation, appropriate to recommend screening mammography at routine
or a first-degree relative of gene intervals (see BSCR-2 and BSCR-3).
mutation carrier who remains • The use of screening ultrasound alone has not been evaluated
untested as a method to reduce breast cancer mortality in individuals who
• Individuals who received thoracic are at increased risk for breast cancer and pregnant.
RT between ages 10 and 30 years • Contrast-enhanced breast MRI is not recommended during
• Individuals with a residual lifetime pregnancy due to the trans-placental passage of gadolinium, and
risk ≥20% as defined by models potential concerns of exposure of gadolinium to the fetus. Non-
that are largely dependent on contrast MRI is not recommended due to lack of sensitivity.
family historya
• Individuals with ADH or lobular
neoplasia (LCIS/ ALH) and ≥20%
residual lifetime risk.
R = Recommended, NR = Not recommended, O = Optional, depending on individual circumstances.

a There b Tomosynthesis can decrease call back rates and improve cancer detection
are significant limitations in interpretation of PRS. PRS should not be used
for clinical management at this time and use is recommended in the context of a compared with 2D mammography alone.
c Consider supplemental screening for those with heterogeneous or extremely
clinical trial, ideally including diverse populations.
dense breasts.

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MANAGEMENT OF BREAST CANCER SCREENING AND BREAST SYMPTOMS DURING PREGNANCY (Continued)

Tomosynthesisb
Management of Palpable R O R NR • Age-appropriate evaluation of a palpable symptom during

Breast Symptom pregnancy should proceed similar to that outlined in BSCR-6.
• Begin evaluation of palpable breast symptom during
pregnancy with breast ultrasound. However, mammography
is an appropriate breast imaging modality if the provider
or radiologist believes that it will add important clinical
information.
• While there is a small theoretical concern of milk fistula with
biopsy, image-guided core needle biopsy should proceed in
the usual prompt timeframe following a BI-RADS 4 or
BI-RADS 5 imaging result during pregnancy.
• Contrast-enhanced breast MRI is not recommended during
pregnancy due to the trans-placental passage of gadolinium,
and potential concerns of exposure of gadolinium to the
fetus. Non-contrast MRI is not recommended due to lack of
sensitivity.
b Tomosynthesis can decrease call back rates and improve cancer detection compared with 2D mammography alone.

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Tomosynthesisb
Management of Abnormal R O R NR • Because of the frequency of normal nipple discharge during

Nipple Discharge pregnancy, abnormal nipple discharge is defined as: Persistent,
spontaneous uni-ductal, unilateral bloody or clear nipple discharge.
• Due to normal physiologic changes of pregnancy, bloody nipple
discharge is common, but usually short-lived (eg, 1 or 2 episodes).
Persistence beyond 1 or 2 episodes should undergo evaluation.
• Begin evaluation of abnormal nipple discharge during pregnancy
with breast ultrasound. However, mammography is an appropriate
breast imaging modality if the provider or radiologist believes that it
will add important clinical information.
• While there is a small theoretical concern of milk fistula with biopsy,
image-guided core needle biopsy should proceed in the usual
prompt timeframe following a BI-RADS 4 or
• If there is persistent bloody nipple discharge without abnormal
breast imaging, a breast surgical expert should be consulted to
discuss possible further diagnostic testing (eg, duct excision).
pregnancy due to the trans-placental passage of gadolinium, and
potential concerns of exposure of gadolinium to the fetus. Non-
contrast MRI is not recommended due to lack of sensitivity.

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Tomosynthesisb
Breast Erythema or R O R NR • Breast erythema or suspicious skin changes should undergo age-
Suspicious Skin Changes appropriate breast imaging evaluation similar to that outlined on
(eg, thickening or edema) (BSCR-10).
• Begin evaluation of erythema during pregnancy with breast ultrasound.
However, mammography is an appropriate breast imaging modality
if the provider or radiologist believes that it will add important clinical
information.
• Contrast-enhanced breast MRI is not recommended during pregnancy
due to the transplacental passage of gadolinium,and potential concerns
of exposure of gadolinium to the fetus. Non-contrast MRI is not
recommended due to lack of sensitivity.
Persistent, Focal Breast R O R NR • While breast pain is common due to the physiologic changes of pregnancy
Pain and is considered normal, focal persistent breast pain (defined as 4 to
6 weeks duration) should undergo evaluation similar to that outlined on
(BSCR-10).
• Begin evaluation of persistent, focal breast pain during pregnancy with
breast ultrasound. However, mammography is an appropriate breast
imaging modality if the provider or radiologist believes that it will add
important clinical information.
• While there is a small theoretical concern of milk fistula with core needle
biopsy, image-guided biopsy should proceed in the usual prompt
timeframe following a BI-RADS 4 or BI-RADS 5 imaging result during
pregnancy.
• Contrast-enhanced breast MRI is not recommended during pregnancy
due to the transplacental passage of gadolinium and potential concerns
of exposure of gadolinium to the fetus. Non-contrast MRI is not
recommended due to lack of sensitivity.

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Tomosynthesisb
BI-RADS Category 3 Rǂǂ Rǂ Rǂ NR • Pregnancy should not change the management of follow-up
Imaging Follow-up of a BI-RADS 3 finding, and appropriate follow-up imaging
(BSCR-18) and/or examination should proceed as outlined in BSCR-18.
• In the case of a BI-RADS 3 finding on MRI without associated
ultrasound or mammography findings, a breast expert should
be consulted to assist with counseling regarding follow-up and
management recommendations (eg, defer to after pregnancy).
Management of Axillary R R R NR • The development of an axillary mass during pregnancy may

Mass be due to normal breast enlargement that occurs during
pregnancy in accessory axillary breast tissue that are present
in ~15% of individuals. It is not uncommon for this to be
asymmetric.
• If after clinical examination there remains concern that the

physical findings are not due to normal axillary breast tissue
that has enlarged due to pregnancy, providers should proceed
with evaluation as outlined in BSCR-13.

pregnancy due to the transplacental passage of gadolinium
and potential concerns of exposure of gadolinium to the
fetus. Non-contrast MRI is not recommended due to lack of
sensitivity.
R = Recommended.
NR = Not recommended.
ǂRecommended if this is the imaging modality that initially resulted in the BI-RADS 3 finding.
ǂǂIf an abnormal CBE finding was associated with the BI-RADS 3 imaging result, it may be appropriate to repeat CBE.

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MANAGEMENT OF BREAST CANCER SCREENING AND BREAST SYMPTOMS DURING LACTATION

Tomosynthesisb
Average Risk Screening in Individuals ≥40 R R NRc NR • While there is both decreased sensitivity and specificity of screening
Years mammography during lactation, there is no contraindication to
screening mammography during lactation.
• A short delay in routine breast imaging may be implemented until
after lactation, in those with average risk of getting breast cancer
based on prior imaging results particularly if they are not planning
prolonged breastfeeding
• It is recommended to either pump the milk or breastfeed just prior to
imaging to improve sensitivity and comfort of the examination
Increased Risk R R NR R • In individuals who are at increased risk for breast cancer, it is
• Individuals with a genetic mutation, or appropriate to recommend screening mammography at routine
a first-degree relative of gene mutation intervals (see BSCR-2 and BSCR-3).
carrier who remains untested • The use of screening ultrasound alone has not been evaluated as a
• Individuals who received thoracic method to reduce breast cancer mortality in individuals who are at
RT between ages 10 and 30 years increased risk for breast cancer and lactating.
Individuals with a residual lifetime risk • In individuals who are at increased risk for breast cancer, it is
≥20% as defined by models that are appropriate to recommend screening breast MRI at routine intervals
largely dependent on family history.a (see BSCR-2 and BSCR-3).
• Individuals with ADH or lobular neoplasia There is minimal excretion of gadolinium into human breast milk,
(LCIS/ ALH) and ≥20% residual lifetime with less than 1% of permitted neonatal dose of contrast over the
risk. first 24 hours after maternal administration. Breast MRI appears
to be highly sensitive for the detection of known PABC and may
proceed if due during lactation in individuals who are at increased
risk for breast cancer.
imaging to improve sensitivity and comfort of the examination.
R = Recommended, NR = Not recommended.

a There are significant limitations in interpretation of PRS. PRS should not be used for clinical management at this time and use is recommended in the context of a
clinical trial, ideally including diverse populations.
c Consider supplemental screening for those with heterogeneous or extremely dense breasts.

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MANAGEMENT OF BREAST CANCER SCREENING AND BREAST SYMPTOMS DURING LACTATION (Continued)

Tomosynthesisb
Management of Palpable R R R NR • Age-appropriate evaluation of a palpable symptom during

Breast Symptom lactation should proceed similar to that outlined in BSCR-6
and BSCR-7.
• It is recommended to either pump the milk or breastfeed just
prior to imaging to improve sensitivity and comfort of the
examination
core needle biopsy, image-guided biopsy should proceed in
BI-RADS 5 imaging result during lactation.

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Tomosynthesisb
Management of Abnormal R R R O • Nipple discharge is normal during lactation. Abnormal nipple
Nipple Discharge discharge is defined as: persistent (see next bullet), spontaneous,
uniductal, unilateral bloody or clear nipple discharge.
• Due to normal physiologic changes of pregnancy, bloody nipple
discharge is common during lactation, but usually short-lived (eg, 1
or 2 episodes). Persistence of bloody nipple discharge beyond 1 or
2 episodes should undergo evaluation.
• Age-appropriate evaluation of abnormal nipple discharge during
lactation should proceed similar to that outlined in BSCR-9.
core needle biopsy, biopsy should proceed in the usual prompt
timeframe following a BI-RADS 4 or BI-RADS 5 imaging result
during lactation.
• If there is persistent bloody nipple discharge without abnormal
breast imaging, a breast surgical expert should be consulted to
discuss possible further diagnostic testing (eg, duct excision).
• Breast MRI is not contraindicated for the management of abnormal
nipple discharge during lactation if clinically indicated.
imaging to improve sensitivity and comfort of the examination.

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Tomosynthesisb
Breast Erythema or R O R O • Breast erythema or suspicious skin changes may be due to

Suspicious Skin Changes puerperal mastitis and all patients should undergo evaluation
(eg, thickening or edema) and, if clinically consistent with mastitis, appropriate treatment
should proceed, including the use of antimicrobials.
• In some circumstances, breast erythema or suspicious skin
changes without other evidence of mastitis (absence of pain
or fever) may prompt immediate evaluation for inflammatory
breast cancer.
• Failure to resolve mastitis with usual treatment should result
in an in-person evaluation for alternative etiologies (eg,
breast abscess, inflammatory breast cancer).
Breast imaging is nearly always indicated to assist in the
diagnosis of persistent breast erythema or skin changes
that have failed usual treatment for mastitis. In this
circumstance, age-appropriate evaluation should proceed
similar to that outlined on (BSCR-10).
Breast ultrasound is particularly useful in diagnosing breast
abscess and may be the appropriate first imaging modality
and if found, drainage is usually indicated and provides a
definitive diagnosis.
However, if a breast abscess is not definitively identified,
individuals should promptly undergo evaluation for
inflammatory breast cancer (BSCR-10).
examination
R = Recommended, O = Optional, depending on individual circumstances.

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Tomosynthesisb
Persistent, Focal Breast R R R NR • While breast pain is common due to the physiologic changes of
Pain lactation and is considered normal, focal persistent (defined as
4 to 6 weeks duration) breast pain should undergo evaluation
similar to that outlined on (BSCR-11).
• Begin evaluation of persistent, focal breast pain during
lactation with breast ultrasound. However, mammography
is an appropriate breast imaging modality if the provider
or radiologist believes that it will add important clinical
information.
core needle biopsy, image-guided biopsy should proceed in
• While breast MRI is not contraindicated for the management
of persistent, focal breast pain during lactation, it is usually not
indicated.
examination

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Tomosynthesisb
BI-RADS Category 3 Rǂǂ Rǂ Rǂ NRǂǂǂ • Lactation should not change the management of follow-up of
Imaging Follow-up a BI-RADS 3 finding, and appropriate follow-up imaging and/
(BSCR-18) or examination should proceed as outlined in BSCR-18.
examination.
Management of Axillary R R R O • The development of an axillary mass during lactation is not

Mass During Lactation uncommon and may be due to normal lactational changes
in accessory axillary breast tissue that are present in
~15% of individuals. It is also not uncommon for this to be
asymmetric. The development of an axillary mass within the
first 2 weeks following delivery is clinically consistent with
lactational changes due to the presence of axillary breast
tissue.
• If after clinical examination there remains concern that the
physical findings are not due to normal axillary breast tissue,
providers should proceed with evaluation as outlined in
BSCR-13.
examination.
R = Recommended.
NR = Not recommended.
O = Optional, depending on individual circumstances.
ǂRecommended if this is the imaging modality that initially resulted in the BI-RADS 3 finding.
ǂǂIf an abnormal CBE finding was associated with the BI-RADS 3 imaging result, it may be appropriate to repeat CBE.
ǂǂǂ Recommended if MRI was the imaging modality that initially resulted in the BI-RADS 3 finding and there are no ultrasound or mammographic correlates.

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MAMMOGRAPHIC ASSESSMENT CATEGORY DEFINITIONS1,2

BI-RADS® - MAMMOGRAPHY FINDINGS
A. Assessment Is Incomplete:
Category 0: Incomplete - Need Additional Imaging Evaluation and/or Prior Mammograms for Comparison:
There is a finding for which additional evaluation is needed. This is almost always used in a screening situation. Under certain circumstances
this assessment category may be used in a diagnostic mammography report, such as when ultrasound equipment or personnel are not
immediately available, or when the patient is unable or unwilling to wait for completion of a full diagnostic examination. A recommendation
for additional imaging evaluation includes the use of spot compression (with or without magnification), special mammographic views,
and ultrasound. Category 0 should not be used for diagnostic breast imaging findings that warrant further evaluation with MRI. Rather,
the interpreting physician should issue a final assessment in a report that is made before the MRI examination is performed. In most
circumstances and when feasible, if a mammography examination is not assessed as negative or benign, the current examination should
be compared with prior examination(s). The interpreting physician should use judgment on how vigorously to attempt obtaining prior
examinations, given the likelihood of success of such an endeavor and the likelihood that comparison will affect the final assessment. In this
context, it is important to note that comparison with previous examination(s) may be irrelevant when a finding is inherently suspicious for
malignancy.
Category 0 should be used for prior image comparison only when such comparison is required to make a final assessment. When category 0
is used in the context of awaiting prior examinations for comparison, there should be in place a tracking procedure guaranteeing with 100%
reliability that a final assessment will be made within 30 days (preferably sooner) even if prior examinations do not become available. Some
mammography practices may reasonably choose never to use category 0 in the context of awaiting prior examinations simply because they
do not have a 100% reliable tracking procedure. If a mammography examination is assessed as category 0 in the context of awaiting prior
examinations and then the prior examinations do become available, an addendum to the initial mammography report should be issued,
including a revised assessment. For auditing purposes, the revised assessment should replace the initial assessment.
1 Mammography results are mandated to be reported using Final Assessment categories (Quality Mammography Standards: Final Rule. Federal Register.
1997;62:55988).
2 Terminology in this table is reflective of the American College of Radiology (ACR). ACR-BI-RADS®--5th Edition. ACR Breast Imaging Reporting and Data System,
Breast Imaging Atlas; BI-RADS®. Reston VA. American College of Radiology, 2014. For more information, see www.acr.org.
Reprinted with permission from the American College of Radiology. No other representation of this document is authorized without express, written permission from the
American College of Radiology.
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B. Assessment Is Complete - Final Assessment Categories:

Category 1: Negative:
There is nothing to comment on. This is a normal examination.
Category 2: Benign:
Like Category 1, this is a "normal" assessment, but here, the interpreter chooses to describe a benign finding in the mammography report.
Involuting, calcified fibroadenomas, skin calcifications, metallic foreign bodies (such as core biopsy and surgical clips), and fat-containing
lesions (such as oil cysts, lipomas, galactoceles, and mixed-density hamartomas) all have characteristically benign appearances and may
be described with confidence. The interpreter may also choose to describe intramammary lymph nodes, vascular calcifications, implants,
or architectural distortion clearly related to prior surgery while still concluding that there is no mammographic evidence of malignancy. On
the other hand, the interpreter may choose not to describe such findings, in which case the examination should be assessed as negative
(category 1).
Note that both category 1 and category 2 assessments indicate that there is no mammographic evidence of malignancy. Both should be
followed by the management recommendation for routine mammography screening. The difference is that category 2 should be used when
describing one or more specific benign mammographic findings in the report, whereas category 1 should be used when no such findings are
described (even if such findings are present).
1997;62:55988).
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Category 3: Probably Benign:

A finding assessed using this category should have a ≤2% likelihood of malignancy, but greater than the essentially 0% likelihood of
malignancy of a characteristically benign finding. A probably benign finding is not expected to change over the suggested period of imaging
surveillance, but the interpreting physician prefers to establish stability of the finding before recommending management limited to routine
mammography screening.
There are several prospective clinical studies demonstrating the safety and efficacy of periodic mammographic surveillance instead of biopsy
for specific mammographic findings.
Three specific findings are validated as being probably benign (the noncalcified circumscribed solid mass, the focal asymmetry, and solitary
group of punctate calcifications). All the previously cited studies emphasize the need to conduct a complete diagnostic imaging evaluation
before making a probably benign (category 3) assessment; hence, it is recommended not to render such an assessment in interpreting a
screening mammography examination. The practice of rendering category 3 assessments directly from screening examination also has been
shown to result in adverse outcomes: 1) unnecessary follow-up of many lesions that could have been promptly assessed as benign; and 2)
delayed diagnosis of a small number of cancers that otherwise may have been smaller in size and less likely to be advanced in stage. Also,
all the previously cited studies exclude palpable lesions, so the use of a probably benign assessment for a palpable lesion is not supported
by robust scientific data, although there are two single-institution studies that do report successful outcomes for palpable lesions. Finally,
because evidence from previously cited studies indicates the need for biopsy rather than continued surveillance when a probably benign
finding increases in size or extent, it is not prudent to render a category 3 assessment when a finding that otherwise meets “probably benign”
imaging criteria is either new or has increased in size or extent.
While the vast majority of probably benign findings are managed with an initial short-interval follow-up (6-month) examination followed by
additional examinations until long-term (2- or 3-year) stability is demonstrated, there may be occasions in which a biopsy is done instead
(patient preference or overriding clinical concern).
1997;62:55988).
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Category 4: Suspicious:
This category is reserved for findings that do not have the classic appearance of malignancy but are sufficiently suspicious to justify a
recommendation for biopsy. The ceiling for category 3 assessment is a 2% likelihood of malignancy and the floor for category 5 assessment
is 95%, so category 4 assessments cover the wide range of likelihood of malignancy in between. Thus, almost all recommendations of
breast interventional procedures will come from assessments made using this category. By subdividing category 43 into 4A, 4B, and 4C, as
recommended in Guidance chapter and using the cut point indicated therein, it is hoped that patients and referring clinicians will more readily
make informed decisions on the ultimate course of action.
Category 5: Highly Suggestive of Malignancy:

These assessments carry a very high probability (≥95%) of malignancy. This category initially was established to involve lesions for which
1-stage surgical treatment was considered without preliminary biopsy, in an era when preoperative wire localization was the primary breast
interventional procedure. Nowadays, given the widespread acceptance of imaging-guided percutaneous biopsy, 1-stage surgery is rarely,
if ever, performed. Rather, current oncologic management almost always involves tissue diagnosis of malignancy via percutaneous tissue
sampling to facilitate treatment options, such as when sentinel node biopsy is included in surgical management or when neoadjuvant
chemotherapy is administered prior to surgery. Therefore, the current rationale for using a category 5 assessment is to identify lesions for
which any non-malignant percutaneous tissue diagnosis is automatically considered discordant, resulting in the recommendation for repeat
(usually surgical) biopsy.
Category 6: Known Biopsy - Proven Malignancy:

This category is reserved for examinations performed after biopsy proof of malignancy (imaging performed after percutaneous biopsy
but prior to complete surgical excision) in which there are no mammographic abnormalities other than the known cancer that might need
additional evaluation.
1997;62:55988).
3 The new BI-RADS® cut points for the risk of malignancy are as follows: 4A (>2% – ≤10%), 4B (>10% – ≤50%), 4C (>50% – <95%).
Reprinted with permission for the American College of Radiology. No other representation of this document is authorized without express, written permission from the
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ULTRASOUND ASSESSMENT CATEGORY DEFINITIONS1,2

BI-RADS® - ULTRASOUND FINDINGS
A. Assessment Is Incomplete:
Category 0: Incomplete - Need Additional Imaging Evaluation:
There is a finding for which additional imaging evaluation is needed. This is almost always used in a screening situation. In this context,
additional imaging evaluation includes the recording of (nonstandard) ultrasound images to supplement the standard images recorded for a
screening examination. Note that this does not include repeat real-time scanning by the interpreting physician and/or colleague as long as
additional images are not recorded. This respects the unique real-time nature of ultrasound and does not penalize its use.
Under certain circumstances, assessment category 0 may be used in a diagnostic ultrasound report, such as when equipment or personnel
are not immediately available to perform a needed concurrent diagnostic mammography examination, or when the patient is unable or
unwilling to wait for completion of a full diagnostic examination. Category 0 should not be used for diagnostic breast imaging findings that
warrant further evaluation with MRI. Rather, the interpreting physician should issue a final assessment in a report that is made before the MRI
examination is performed.
In most circumstances and when feasible, if a screening ultrasound examination is not assessed as negative or benign, the current
examination should be compared to prior examination(s), if any exist. The interpreting physician should use judgment on how vigorously
to attempt obtaining prior examinations, given the likelihood of success of such an endeavor and the likelihood that comparison will affect
the final assessment. In this context, it is important to note that comparison to previous examination(s) may be irrelevant when a finding is
inherently suspicious for malignancy.
Category 0 should be used for prior image comparison only when such comparison is required to make a final assessment. When category
0 is used in the context of awaiting prior examinations for comparison, there should be in place a tracking system guaranteeing with 100%
reliability that a final assessment will be made within 30 days (preferably sooner), even if prior examinations do not become available. Some
breast imaging practices may reasonably choose never to use category 0 in the context of awaiting prior examinations simply because
they do not have a 100% reliable tracking system. If an ultrasound examination is assessed as category 0 in the context of awaiting prior
examinations and then the prior examinations do become available, an addendum to the initial ultrasound report should be issued, including
a revised assessment. For auditing purposes, the revised assessment should replace the initial assessment.
A need for previous studies to determine appropriate management might also temporarily defer a final assessment.
1997;62:55988).
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B. Assessment Is Complete — Final Categories:

Category 1: Negative:
There is nothing to comment on. This is a normal examination.
Category 2: Benign:
As with category 1, this is a “normal” assessment, but here the interpreter chooses to describe a benign finding in the ultrasound report.
For example, the interpreter may choose to describe one or more simple cysts, intramammary lymph nodes, postsurgical fluid collections,
breast implants, or complicated cysts/probable fibroadenomas that are unchanged for at least 2 or 3 years, while still concluding that there
is no sonographic evidence of malignancy. On the other hand, the interpreter may choose not to describe such findings, in which case the
examination should be assessed as negative (category 1).
Note that both category 1 and category 2 assessments indicate that there is no sonographic evidence of malignancy. Both should be followed
by the management recommendation for routine age-appropriate screening. The difference is that category 2 should be used when describing
one or more specific benign sonographic findings in the report, whereas category 1 should be used when no such findings are described
(even if such findings are present).
1997;62:55988).
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Category 3: Probably Benign:

Assessment category 3, probably benign, is not an indeterminate category for use simply when the radiologist is unsure whether to render
a benign (BI-RADS® category 2) or suspicious (BI-RADS® category 4) assessment, but is one that is reserved for specific imaging findings
known to have >0% but ≤2% likelihood of malignancy. For ultrasound, there is robust evidence that a solid mass with a circumscribed margin,
oval shape, and parallel orientation (most commonly fibroadenoma) and an isolated complicated cyst have a likelihood of malignancy in the
defined (≤2%), probably benign range, for which short-interval (6-month) follow-up sonography and then periodic sonographic surveillance
may represent appropriate management. Similar data have been reported for clustered microcysts, but these data are less strong because
they involve much fewer cases. The use of assessment category 3 for sonographic findings other than these three should be considered only
if the radiologist has personal experience to justify a watchful-waiting approach, preferably involving observation of a sufficient number of
cases of an additional sonographic finding to suggest a likelihood of malignancy within the defined (≤2%), probably benign range.
This edition of the BI-RADS® Atlas also emphasizes the recommendation that a category 3 assessment should not be made at screening;
rather, this should be done only after completion of full diagnostic breast imaging examination. This recommendation is appropriate for
screening mammography, for which batch interpretation usually is utilized, because in this setting there is no opportunity to complete the
diagnostic workup before interpreting the screening examination. However, screening ultrasound almost always is interpreted online, so
a full diagnostic examination also is completed while the patient remains in the breast imaging facility, and a single breast imaging report
may be issued that combines the findings of both screening and diagnostic components of the examination. Hence, there is no purpose in
recommending against category 3 assessment at screening ultrasound, because the diagnostic workup would be completed simultaneously.
Note that for auditing purposes, the screening component of a category 3-assessed screening ultrasound examination will be audit-positive,
not only because additional nonstandard (diagnostic) images will be recorded but also because a category 3 assessment at screening is
defined as being audit-positive.
1997;62:55988).
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For category 3 assessments, the initial short-term follow-up interval is usually 6 months and involves the breast(s) containing the probably
benign finding(s). Assuming stability at this 6-month examination, a category 3 assessment again is rendered with a management
recommendation for a second short-interval follow-up examination in 6 months. Again assuming stability at this second short-interval follow-
up, the examination is once more assessed as category 3, but now the recommended follow-up interval usually is lengthened to 1 year due
the already-observed 12-month stability. Note that although the 1-year follow-up coincides with the routine screening interval in the United
States, a category 3 assessment is rendered to indicate that the period of imaging surveillance is still underway. As with surveillance using
mammography, after 2 to 3 years of stability, the final assessment category should be changed to benign (BI-RADS® category 2). A benign
evaluation may also be rendered before completion of category 3 analysis if, in the opinion of the interpreter, the finding has no chance of
malignancy and is thus a category 2.
Category 4: Suspicious:
This category is reserved for findings that do not have the classic appearance of malignancy but are sufficiently suspicious to justify a
recommendation for biopsy. The ceiling for category 3 assessment is a 2% likelihood of malignancy, and the floor for category 5 assessment
is 95%, so category 4 assessments cover the wide range of likelihood of malignancy in between. Thus, almost all recommendations for breast
interventional procedures will come from assessments made using this category. By subdividing category 43 into 4A, 4B, and 4C, it is hoped
that patients and referring clinicians will more readily make informed decisions on the ultimate course of action.
1997;62:55988).
3 The new BI-RADS® cut points for the risk of malignancy are as follows: 4A (>2% – ≤10%), 4B (>10% – ≤50%), 4C (>50% – <95%).
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Category 5: Highly Suggestive of Malignancy:

These assessments carry a very high probability (≥95%) of malignancy. This category initially was established to involve lesions for which
1-stage surgical treatment could be considered without preliminary biopsy in an era when preoperative wire localization was the primary
breast interventional procedure. Nowadays, given the widespread acceptance of imaging-guided percutaneous biopsy, 1-stage surgery
rarely, if ever, is performed. Rather, current oncologic management almost always involves tissue diagnosis of malignancy via percutaneous
tissue sampling to facilitate treatment options, such as when sentinel node imaging is included in surgical management or when neoadjuvant
chemotherapy is administered prior to surgery. Therefore, the current rationale for using a category 5 assessment is to identify lesions
for which any nonmalignant percutaneous tissue diagnosis is considered discordant, resulting in the recommendation for repeat (usually
vacuum-assisted or surgical) biopsy. Also note that whereas the fourth edition simply indicated that “appropriate action should be taken”
as management for category 5 assessments, the fifth edition provides the more directed management recommendation that “biopsy
should be performed in the absence of clinical contraindication.” This new text unequivocally specifies tissue diagnosis as the interpreting
physician’s management recommendation for category 5 assessments, appropriately and effectively transferring the burden of establishing a
contraindication to this recommendation to the referring clinician.
Category 6: Known Biopsy-Proven Malignancy:

This category is reserved for examinations performed after biopsy proof of malignancy (imaging performed after percutaneous biopsy but
prior to surgical excision), in which there are no abnormalities other than the known cancer that might need additional evaluation.
1997;62:55988).

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ABBREVIATIONS
ADH atypical ductal hyperplasia
AMAB assigned male at birth
ALH atypical lobular hyperplasia
CBE clinical breast exam

CEM contrast-enhanced mammography
FEA flat epithelial atypia
LCIS lobular carcinoma in situ
MBI molecular breast imaging
PABC pregnancy-associated breast cancers

PRS polygenic risk scores
RT radiation therapy
ABBR-1

Table of Contents
NCCN Categories of Evidence and Consensus

Category 1 Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2A Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2B Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
Category 3 Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise indicated.

CAT-1
NCCN Guidelines Version 1.2023

Breast Cancer Screening and Diagnosis
Discussion This discussion is being updated to correspond with the Breast Pain ............................................................................MS-22
newly updated algorithm. Last updated 10/04/18.
Axillary Mass ..........................................................................MS-22
Table of Contents
Table 1: Breast Cysts - Types and Definitions ............................MS-24
Overview ..................................................................................... MS-2
References ................................................................................MS-25
Literature Search Criteria and Guidelines Update Methodology .... MS-2
Breast Screening Components .................................................... MS-3
Clinical Encounter .................................................................... MS-3
Breast Cancer Risk Assessment .............................................. MS-4
Breast Imaging Modalities ........................................................ MS-4
Screening Recommendations for Women at Average Risk ........... MS-6
Women with Average Risk Between the Ages of 25 and 39 ...... MS-6
Women with Average Risk 40 Years and Older: ....................... MS-7
Screening Recommendations for Women at Increased Risk ...... MS-12
Diagnostic Evaluation ................................................................ MS-14
Diagnostic Imaging After Screening Mammography Recall ..... MS-15
Breast Tissue Biopsy ............................................................. MS-16
Diagnostic Evaluation for Symptomatic Findings on Physical

Examination ........................................................................... MS-17
Palpable Mass in the Breast ................................................... MS-18
Nipple Discharge Without a Palpable Mass ............................ MS-20
Asymmetric Thickening or Nodularity ..................................... MS-21
Skin Changes ........................................................................ MS-21

MS-1
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.

chosen as it remains the most widely used resource for medical literature
Overview
and indexes peer-reviewed biomedical literature.
The average lifetime risk of breast cancer for a female in the United States
has been estimated at 12.3% (ie, 1 in 8 females).1 For 2018, the American Search results were confined to the following article types: Clinical Trial,
Cancer Society (ACS) estimates that 63,960 cases of female carcinoma in Phase II; Clinical Trial, Phase III; Clinical Trial, Phase IV; Guideline;
situ of the breast and 268,670 cases of invasive breast cancer (266,120 in Randomized Controlled Trial; Meta-Analysis; Systematic Reviews; and
females and 2,550 in males) will be diagnosed in the United States.2 About Validation Studies.
41,400 deaths are estimated for 2018.3 The good news is that death rates
have been falling an average of 1.8% each year over the course of 2006 The potential relevance of the PubMed search citations over the past year
through 2015.4 This decrease has been attributed to mammographic was examined. The data from key PubMed articles as well as articles from
screening and treatment advances.5 additional sources deemed as relevant to these Guidelines and/or
discussed by the panel have been included in this version of the
The National Comprehensive Cancer Network (NCCN) Clinical Practice Discussion section (eg, e-publications ahead of print, meeting abstracts).
Guidelines in Oncology® (NCCN Guidelines®) for Breast Cancer Any recommendations for which high-level evidence is lacking are based
Screening and Diagnosis are for facilitating clinical decision-making. The on the panel’s review of lower-level evidence and expert opinion.
general public and health care providers need to be aware that
mammography or any other imaging modality is not a stand-alone The complete details of the development and update of the NCCN
procedure. Neither the current technology of mammography or other Guidelines are available at www.NCCN.org.
imaging tests nor the subsequent interpretation of such tests is foolproof.
Clinical judgment is needed to ensure appropriate management. The
Sensitive/Inclusive Language usage
patient’s concerns and physical findings must be taken into account along NCCN Guidelines strive to use language that advances the goals of
with imaging results and histologic assessment. equity, inclusion, and representation. NCCN Guidelines endeavor to use
language that is person-first; not stigmatizing; anti-racist, anti-classist,
Literature Search Criteria and Guidelines Update anti-misogynist, anti-ageist, anti-ableist, and anti-weight-biased; and
Methodology inclusive of individuals of all sexual orientations and gender identities.
NCCN Guidelines incorporate non-gendered language, instead focusing
Before the update of this version of the NCCN Guidelines for Breast
on organ-specific recommendations. This language is both more accurate
Cancer Screening and Diagnosis, an electronic search of the PubMed
and more inclusive and can help fully address the needs of individuals of
database was performed to obtain key literature using the following
all sexual orientations and gender identities. NCCN Guidelines will
search terms: breast cancer screening; screening mammography; breast
continue to use the terms men, women, female, and male when citing
cancer diagnosis. The search results were narrowed by selecting studies
statistics, recommendations, or data from organizations or sources that do
in humans published in English. An updated search was carried out
not use inclusive terms. Most studies do not report how sex and gender
before the publication of this document. The PubMed database was
data are collected and use these terms interchangeably or inconsistently.
MS-2

If sources do not differentiate gender from sex assigned at birth or organs screening have not been performed. Rationale for recommending the
present, the information is presumed to predominantly represent cisgender clinical encounter is to maximize the earliest detection of breast cancers.
individuals. NCCN encourages researchers to collect more specific data in Overdiagnosis and overtreatment is not a significant issue with CBE, as
future studies and organizations to use more inclusive and accurate the majority of palpable cancers found on a CBE are invasive cancers.
language in their future analyses. CBE is an important component of a clinical encounter and is important in
order to detect early-stage palpable cancers, especially those that are
Breast Screening Components mammographically occult (eg, lobular carcinomas). According to the
Breast screening is performed in individuals assigned female at birth NCCN Panel, inspection of the breasts should be performed with the
(AFAB) without any signs or symptoms of breast cancer so that disease patient in both upright and supine positions. Positioning may be done so
can be detected as early as possible, which allows early treatment to as to elicit any subtle shape or contour changes in the breast.6
reduce the mortality and morbidity associated with the disease. A
diagnostic breast evaluation differs from breast screening in that it is used Breast Awareness: Individuals AFAB should be familiar with their breasts
to evaluate an existing problem (eg, palpable mass, discharge from the and any changes to them.7,8 Data from a large randomized trial of breast
nipple). self-examination (BSE) screening have shown that instruction in BSE has
no effect on reducing breast cancer mortality. In this study, 266,064
The components of a breast screening evaluation are dependent on age females of Chinese descent who were not undergoing routine
and other factors such as medical and family history, and can include mammographic screening were randomized to either receive instruction in
breast awareness (ie, patient familiarity with their breasts); regular clinical BSE or not.9 Compliance was encouraged through feedback and
encounters, which include breast cancer risk assessment and clinical reinforcement sessions. After 10 to 11 years of follow-up, 135 breast
breast exam (CBE); breast imaging with screening mammography; and, in cancer deaths in the group that received instruction and 131 in the control
selected cases, breast MRI. group were observed. The cumulative breast cancer mortality rates were
not significantly different between the two arms (relative risk [RR], 1.04;
Clinical Encounter 95% CI, 0.82–1.33; P = .72). The number of benign breast lesions
The starting point of these guidelines for screening and evaluating breast detected in the BSE instruction group was higher than that detected in the
abnormalities is a clinical encounter, which includes a complete medical control group. Nevertheless, individuals should be encouraged to be
history followed by breast cancer risk assessment and a CBE. The aware of their breasts since this may facilitate detection of interval cancers
frequency of the clinical encounter depends on the age and risk between routine screenings. The NCCN Panel recommends breast
assessment of the patient. awareness, specifically that all individuals AFAB should be familiar with
their breasts and promptly report any changes to their health care
In a review of controlled trials and case-control studies that included CBE provider.
as part of the screening modality, sensitivity of CBE was found to be 54%
and specificity 94%.6 Randomized trials comparing CBE versus no
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Breast Cancer Risk Assessment procedures.12,13 However, digital mammography was significantly more
If the physical examination is negative in an asymptomatic individual accurate in females <50 years of age with dense breasts, and there was a
AFAB, the next decision point is based on risk stratification. Individuals nonsignificant trend toward improved accuracy of film mammography in
AFAB are stratified into two basic categories of risk for the purpose of those ≥65 years of age. In another trial of females aged 45 to 69 years
screening recommendations: average risk and increased risk of breast randomly assigned to film or digital screening mammography, the latter
cancer. Risk assessment is outlined in the NCCN Guidelines for Breast procedure was shown to result in a higher rate of cancer detection.14
Cancer Risk Reduction. The increased risk category consists of six
More recently, combined use of digital mammography (two-dimensional,
groups: 1) those with a prior history of breast cancer; 2) those ≥35 years
2D) in conjunction with digital breast tomosynthesis (DBT) improves
of age with a 5-year risk of invasive breast cancer ≥1.7% (per Gail
cancer detection and reduces false-positive call-back rates.15-25
Model); 3) those who have a lifetime risk >20% based on history of
Tomosynthesis allows acquisition of three-dimensional (3D) data using a
lobular carcinoma in situ (LCIS) or atypical ductal hyperplasia
moving x-ray and digital detector. These data are reconstructed using
(ADH)/atypical lobular hyperplasia (ALH); 4) those who have a lifetime
computer algorithms to generate thin sections of images. The combined
risk >20% as defined by models that are largely dependent on family
use of 2D and DBT results in double the radiation exposure compared with
history; 5) those between the ages 10 and 30 years with prior thoracic
mammography alone. However, this increase in radiation dose falls below
RT (eg, mantle irradiation); and 6) those with a pedigree suggestive of or
dose limits of radiation set by the U.S. Food and Drug Administration
known genetic predisposition.
(FDA) for standard mammography. The radiation dose can be minimized
Breast Imaging Modalities by newer tomosynthesis techniques that create a synthetic 2D image,
which may obviate the need for a conventional digital image.16,26,27
Screening Mammography
Of the various imaging modalities, mammography remains the most The presence of dense breast tissue decreases the sensitivity of
important as it is the only one to demonstrate a mortality reduction. A mammography to detect small lesions and may obscure visualization of an
screening mammogram typically involves two x-ray images of each breast underlying cancer. In addition, dense breast tissue as measured by
(ie, one taken from the top [craniocaudal] of the breast and the other from mammography is increasingly recognized as an important risk factor for
the side [mediolateral oblique]). Technical aspects of mammography can breast cancer.28-31 About half of all females of screening age have “dense”
affect the quality of screening results. Digital mammography, which has breast tissue referred to as “heterogeneously dense” or “extremely dense”
replaced film-screen mammography in the United States, generates an by American College of Radiology (ACR) Breast Imaging Reporting and
electronic image of the breast and allows for computer storage and Data System (BI-RADS®) nomenclature. The presence of dense tissue is
processing of the image, thereby increasing the ability to detect subtle not abnormal and can change over time. Many states have passed
abnormalities.10,11 legislation mandating patient notification of breast density, but few have
required insurance coverage for supplemental screening.32 The NCCN
In a study of 49,528 females who underwent both film and digital
Panel recommends counseling on the risks and benefits of supplemental
mammography, no difference was seen in the overall accuracy of the two
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screening for individuals AFAB with heterogeneously dense and commonly used for diagnostic follow-up of an abnormality seen on
extremely dense breast tissue.33 Different supplemental imaging screening mammography and palpable clinical concerns.
modalities may be considered based on risk and patient
Screening MRI
values/preference.34
The sensitivity of contrast-enhanced breast MRI at detecting breast cancer
Screening Ultrasound is higher than the sensitivity of mammography, although the specificity of
Due to limitations of mammographic screening, especially in those with the former procedure is often lower, resulting in a higher rate of
dense breasts, other imaging modalities are being explored to supplement false-positive findings.41 In addition, microcalcifications are not detectable
mammography, most commonly ultrasound and MRI. Unlike with MRI.42,43 Similar to screening ultrasound, whether MRI screening
mammographic screening, both technologies lack evidence from impacts survival has not been addressed in randomized clinical trials.
randomized controlled trials (RCTs) of screening efficacy, although Therefore, careful patient selection for additional screening with MRI is
ultrasound is widely used in the diagnostic setting. Most clinical ultrasound needed. Although current evidence does not support the use of breast
screening studies have found increased cancer detection to be MRI to screen females at average risk of breast cancer, the benefits of
incremental to screening mammograms in females with dense breasts; screening MRI for early detection of breast cancer in females at high risk
however, they may increase recall and benign breast biopsies. For of breast cancer, such as those ages 10 through 30 years with a history of
example, a large prospective study in females with dense breasts and prior thoracic radiation, a known genetic predisposition for breast cancer,
elevated risk for breast cancer found that adding screening ultrasound to or a strong family history of the disease have been demonstrated in
mammography identified an additional 4.3 cancers per 1000 females multiple studies.44-52 The ACS has published guidelines recommending use
screened (95% CI, 1.1–7.2 cancers per 1000) but increased the number of of breast MRI as an adjunct to screening mammography in certain
false-positive results.34 Subsequent follow-up studies showed similar populations of females at high risk of breast cancer.53 Nevertheless, a high
results.35,36 However, in females with dense breasts, the mammographic false-positive rate for screening MRI was identified in several studies. For
sensitivity was found to be 50% (95% CI, 33.8%–66.2%) and the example, in one study of females at high risk, many of whom were young
sensitivity of mammography plus ultrasound was 77.5% (95% CI, 61.6%– (age range of entire cohort 35-49 years) and had very dense breast tissue,
89.2%).34 Application of screening ultrasound to females with dense screening MRI led to 3 times as many benign biopsies as
breasts in clinical populations has produced similar results.37 mammography.54
Although there is increasing evidence that breast ultrasonography can be A single retrospective study of asymptomatic females with atypical
useful in the incremental detection of breast cancer as an adjunct to hyperplasia or LCIS enrolled in a high-risk screening program has evaluated
screening mammography in the evaluation of females with dense use of MRI in this population.55 Approximately half of the females underwent
breasts,34,35,38-40 the routine use of ultrasound as a universal supplemental screening with mammography and MRI, whereas the other half was
screening test in individuals AFAB at average risk of breast cancer is not screened with mammography alone. For those undergoing both types of
recommended by the NCCN Panel at this time. Ultrasonography is screening, MRI detected breast cancer in 4% of patients with LCIS who had
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negative mammogram results. MRI screening did not affect the rate of localization of MRI-detected findings. The ACR has published guidelines
cancer detection in females with atypical hyperplasia. Females who for the performance of contrast-enhanced MRI of the breast.63
underwent screening with MRI were more likely to be younger and
Other Breast Imaging Modalities
premenopausal, and to have a stronger family history of breast cancer than
those who were evaluated by mammography alone. However, only one There is emerging evidence that breast scintigraphy and contrast-
female with cancer detected by MRI following a negative mammography enhanced mammography may improve detection of early breast cancers
finding had reported a family history of breast cancer, and no difference was among females with mammographically dense breasts;64-67 current
seen in the percentages of patients who ultimately developed cancer in the evidence does not support their routine use as alternative screening
two groups. procedures. Thermography and ductal lavage are not recommended by
the NCCN Panel for breast cancer screening or diagnosis. The FDA has
Studies have reported that deposits of gadolinium, a component of MRI issued a safety alert stating that ductal lavage should not be a
contrast agents, remain in the brain of some patients who undergo 4 or replacement for mammograms.68
more contrast MRI scans, long after the last administration.56-59 Retention
of gadolinium has also been seen in the bone.60,61 The clinical significance Screening Recommendations for Indivduals AFAB at
and practice implications of these observations are unclear and are being
Average Risk of Breast Cancer
investigated. In 2015, the FDA issued a safety warning alerting that The NCCN Panel recognizes that the primary purpose of screening
investigations were ongoing for the risk associated with gadolinium individuals AFAB at average risk for developing breast cancer is to detect
deposits in the brain following its repeated use with MRI. In 2017, the FDA breast cancer early, which allows treatment to decrease mortality and
issued an update stating that its review of available data had not identified morbidity associated with breast cancer.
adverse health effects from gadolinium retained in the brain.62 Patients will
Those with Average Risk of Breast Cancer Between the Ages of 25 and
be asked to read a medication guide prior to receiving gadolinium.
39:
In individuals AFAB with a history of thoracic radiation between ages 10 The NCCN Panel recommends a clinical encounter, which includes
and 30 years, a known genetic predisposition to breast cancer, or a ongoing breast cancer risk assessment, risk reduction counseling, as
lifetime risk of >20% based on models such as Claus or Tyrer-Cuzick, well as a CBE every 1 to 3 years, and encouraging individuals to be aware
based on current evidence, the NCCN Panel continues to recommend an of their breasts and promptly report any changes to their health care
annual MRI as an adjunct to mammography. Individuals AFAB with LCIS provider.
or ALH/ADH with a lifetime risk of ≥20% should be considered for breast
MRI based on emerging evidence of the benefits. Although the screening CBE by itself does not rule out disease, the high
specificity of certain abnormal findings by highly qualified clinicians
Criteria for the performance/interpretation of high-quality breast MRI increases the probability of finding certain breast cancers (eg, lobular
include a dedicated breast coil, radiologists experienced in breast MRI, carcinoma). The NCCN Panel believes that a clinical encounter provides
and the ability to perform MRI-guided needle sampling and/or wire an opportunity for providers to perform a CBE, conduct a breast cancer
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risk assessment, provide risk reduction recommendations, and counsel on The NCCN Panel continues to support its long-standing recommendation
healthy lifestyles. of annual screening mammography beginning at age 40 years (category
1 recommendation), as it results in the greatest mortality reduction, most
Those with Average Risk of Breast Cancer ≥40 Years of Age: lives saved, and most life years gained.
The NCCN Panel recommends annual clinical encounter, which includes
ongoing breast cancer risk assessment, risk reduction counseling, as The NCCN Panel has not established an upper age limit for screening.
well as a CBE, and encourages individuals to be aware of their breasts According to the panel, if a patient has severe comorbid conditions
and promptly report any changes and annual screening mammography limiting life expectancy and no further intervention would occur based on
(category 1 recommendation) with the consideration of tomosynthesis. the screening findings, then the patient should not undergo screening,
Those electing to undergo screening mammography should be counseled regardless of age.
regarding its potential benefits, risks, and limitations. The NCCN Panel is
in agreement with ACS and other organizations that annual screening Rationale for Mammographic Screening Starting at Age 40:
mammograms in individuals AFAB ≥40 years of age at average-risk of Reduction in breast cancer-related mortality is the major benefit of
breast cancer should be covered by health care payers without additional mammographic screening for breast cancer. This benefit is evident across
cost-sharing or copayments. studies, including RCTs, case-controlled observational studies, and
computer modelling studies.
Mammographic screening and subsequent treatment have been shown to
decrease breast cancer mortality beginning at age 40 years.69,70 Meta- While breast cancer screening guidelines put forth by all the organizations
analysis of invitational RCTs, observational studies, and computer acknowledge mortality reduction benefit from current studies of
modeling of mammographic screening consistently show benefit, although mammography screening in females 40 to 49 years of age, those
the magnitude of benefit has varied in part due to the diversity of study recommending breast cancer screening to begin at age 5070 view the
designs and screening frequency. However, the RCTs are now old and benefits of screening as being balanced by the harms of screening during
may not reflect current mammography technology, interpretation, and this decade. Other organizations, who have recommended screening
oncologic care. Therefore, effectiveness may be better estimated in more commencement at age 45 as a “strong” recommendation, have shown the
modern observational studies. absolute benefit of ages 45 to 49 to be very similar to ages 50 to 54.69
While showing there is benefit of screening for ages 40 to 44, a “qualified”
The mammography screening guidelines put forth by various rather than a “strong” recommendation is given for the younger age group
organizations vary with respect to age to initiate screening, the frequency due to the lower absolute benefit. However, the “qualified”
of screening, and when to stop screening.69,70 The assessment of the recommendation means “most” females would want the earlier screening
benefits of mammography versus the risks based on age are weighed on and only a “small proportion” would not.69
different scales by different organizations.
Benefits of Mammographic Screening:
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Systematic reviews of RCTs have generally shown a reduction in breast It is important to note that the RCTs studying the benefits of screening
cancer mortality with mammography screening.71 mammography used screen film mammography, sometimes using only a
single view. Therefore, they may not reflect results obtained with modern
The UK Age trial specifically studied the effect of film-screen advances in imaging. Digital mammography has been shown to detect
mammographic screening starting at age 40 years.72 A mean of 10.7 years more breast cancers in females with dense breasts, which is common in
of follow-up showed a non-statistically significant breast cancer mortality younger females. The more recent observational studies better quantify
reduction in females invited to screening (RR, 0.83; 95% CI, 0.66–1.04).72 the effectiveness of screening in the context of improved imaging
A follow-up of the UK AGE trial was carried out to study breast cancer techniques.
mortality and incidence at a median of 17.7 years of follow-up, an increase
of 7 years from the previous analysis.73 There continued to be a non- Case-control observational studies have shown benefits of reduction in
significant overall reduction in risk of breast cancer mortality (RR, 0.88; breast cancer mortality ranging from 40% to 45%.75,76 A meta-analysis of
95% CI, 0.74–1.04) during a median of 17 years of follow-up. However, observational case-control studies found a significant reduction in breast
the reduction in breast cancer mortality noted in the first 10 years after cancer mortality with mammographic screening for females aged 40 to
diagnosis was now significant in the group that underwent screening >79 years of age with a 48% mortality reduction (odds ratio [OR] 0.52;
compared with the control group (RR, 0.75, 0.58–0.97).73 Other trials 95% CI, 0.42–0.65) after adjustment for self-selection.77 Relevant to the
included females who were up to age 49 years at the time of entry into the North American population, data from a Canadian study showed a
trial, who were therefore in their 50s during the screening intervention. The mortality reduction of 44% (CI, 33%–55%) among screened females ages
results of the UK Age trial support the importance of annual 40 to 49 years, which was similar to the overall reduction in mortality of
mammography screening in females ages 40 to 49 years of age to reduce 40% (CI, 33%–48%) found among females ages 40 to 79 years.76
breast cancer-related mortality.73
A retrospective analysis evaluating the benefits of mammographic
A Swedish study compared breast cancer mortality rates in females 40 to screening of females aged 40 to 49 years found that mammography-
49 years of age living in different counties. Counties included those that detected breast cancer coincides with lower-stage disease at detection,
invited females for screening starting at age 40 and others that did not resulting in reduced treatment morbidity and lower rates of recurrence.78 A
invite females to be screened at age 40 and started screening at age 50.74 population-based study of data from the Netherlands Cancer Registry
After an average 16 years of follow-up, the investigators observed an estimated the impact of tumor size in females with breast cancer in two
overall 29% mortality reduction (RR, 0.71; 95% CI, 0.62–0.80). For age time intervals: 1999 to 2005 and 2006 to 2012. The year 2005 was used to
groups 40 to 44 and 45 to 59 years, the RR estimates were 0.82 (95% CI, divide the data into two-time intervals studies, because trastuzumab and
0.67–1.00) and 0.63 (95% CI, 0.54–0.75).74 Although the estimated other effective adjuvant therapy were introduced after this year in the
reduction in breast cancer mortality was smaller for ages 40 to 44 Netherlands. The analysis found that tumor size remained a critical
compared with ages 45 to 49, the reduction in mortality seen for ages 40 component of survival even with the availability of new and effective
to 44 was still substantial.74
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systemic therapy options.79 These findings reiterate the fact that potential overdiagnosis to be a “harm.”83 In this study, 63% of females
diagnosing breast cancer at an early stage is important. thought 500 or more false positives per life saved was acceptable.83
The Cancer Intervention and Surveillance Modeling Network (CISNET) The NCCN Panel believes that the harms analysis of mammographic
models from 2009 demonstrate a 29% to 54% (mean 39%) mortality screening is most informative if it includes the net harms of
reduction for annual screening for females ages 40 to 84 years.80 The mammographic screening in individuals who underwent screening versus
CISNET models from 2015, based on digital screening mammography, those who did not. According to the NCCN Panel, the major harm related
show greater mortality reduction benefit.81 Benefits of screening females in to not performing any screening for breast cancer is diagnosis of later-
their 40s are more favorable when considered from the perspective of life stage breast cancer, which may prove to be lethal or require therapy that
years saved compared exclusively to mortality reduction.82 Females in is more extensive. There is evidence showing that females diagnosed with
their 40s have the highest number of life years at risk to be lost due to breast cancer who did not undergo screening had substantially more need
longevity even though their breast cancer risk is smaller. Breast cancer is for chemotherapy and more extensive surgery than females who
the second leading cause of deaths for females in their 40s, trailing only underwent routine screening.84
poisonings.
Furthermore, absence of mammographic screening for breast cancer does
Individuals AFAB should be informed of the evidence demonstrating the not mean absence of breast-related problems. Non-screened females
value of detecting breast cancer early, before symptoms develop. The develop signs and symptoms leading to diagnostic investigation, false-
benefits of early detection include mortality reduction, less aggressive positive biopsies, or potential diagnosis of non-lethal conditions.
treatment, and a wide range of treatment options. Screening also identifies
A mammogram result is often considered a false positive when it prompts
those with atypical hyperplasia or LCIS who may be candidates for risk
additional imaging tests and/or biopsy in an abnormality that is not
reduction therapy to reduce their chance of developing breast cancer.
cancerous. False-positive results can occur at any age. It is important to
Harms of Mammographic Screening: distinguish between recalls from screening and biopsies that result in a
The harms or risk profile for breast cancer screening is weighted false-positive outcome. Recalls are defined by the FDA as “incomplete”
differently by different organizations.69,70 This is a very subjective rating as and not positive. Recalls are resolved by obtaining incremental diagnostic
there are limited data regarding a female’s perspective of the harms of mammographic imaging and/or ultrasound with the vast majority of recalls
screening. The clinical practice guidelines that recommend delaying proving negative and not requiring biopsy. The frequency of recalls from
screening to age 50 and older69 place a greater emphasis on the risks of screening are the same per decade whether screening begins at age 40 or
screening mammography, specifically false-positive results and age 50.70 While recalls are commonly thought to be higher in younger
overdiagnosis. Most females highly value the reduction in breast cancer females, this primarily reflects higher recall rates at the prevalent or initial
mortality, whereas many females do not consider false positives and screen when prior mammograms are not available for comparison and not
the age at which screening commences. Initiating screening
mammography at age 50 would shift this “prevalent” false positive to that
MS-9

decade. Furthermore, the decade-long false-positive biopsy carcinoma in situ (DCIS) is included or excluded. Furthermore,
recommendation rate is somewhat lower when screening begins at age 40 overdiagnosis estimates vary by age and duration of follow-up.
compared to age 50. Less than 1% of screened females per year will be
recommended for a biopsy that proves benign, whether annual screening The most reliable estimates of overdiagnosis would be from RCTs in
commences at age 40 or 50. The vast majority of false-positive biopsies which there was no formal screening offered to the control group for a long
are now performed as outpatient image-guided needle biopsies using local period at the end of the screening period. The Malmo randomized trial, in
anesthesia and are generally well-tolerated and acceptable to females. which the invited cohort group aged 55-69 years was not routinely
screened at the end of the trial,89 showed an overdiagnosis rate of 10%
Those considering false positives as one of the harms of screening note after an average of 15 years follow-up, which included invasive cancer
psychosocial consequence as one of the negative consequences of false and DCIS. The rate was 7% for invasive cancer.89 The National Breast
positives.85 However, a cross-sectional survey of female’s attitudes toward Screening Studies in Canada conducted two randomized trials that
false positives found that females consider false positives as an included a control group that did not receive routine screening at the end
acceptable consequence.83 of the trial. The follow-up period was 13 years. In the first trial, in which
females were aged 40 to 49 years at recruitment, the estimated
Overdiagnosis is the detection of a condition by screening that would not overdiagnosis was 14%. In the second trial, in which females were aged
have become apparent by usual care absent screening. Overdiagnosis 50 to 59 years at recruitment, the estimated overdiagnosis rate was
may lead to overtreatment, which is the more significant problem. It is 11%.90,91 Using these 3 studies, the UK review estimated overdiagnosis
important to understand that overdiagnosis would not influence the age to (including DCIS) to be 10.7%.92 Yet, these studies are limited by their age
initiate screening or the screening interval. The mammographic and differing use of diagnostic mammography among non-screened
abnormality that leads to a potential overdiagnosis does not go away females. However, analysis of the UK AGE trial, which included females
without treatment. If the age to initiate screening is raised from 40 to 45 or aged 40 to 49 years, showed a very low rate of overdiagnosis of 1%,93 a
50 years, or the screening interval is lengthened to biennial, the potential value similar to estimates from Sweden for females in their 40s.74 A
overdiagnosis would occur at the next mammogram that showed the recently reported population-based screening study showed a rate of only
imaging abnormality. 0.3% overdiagnosis after 12 years of follow-up in either invited or uninvited
females (n = 988, 090) and a 46% reduction in breast cancer mortality
Overdiagnosis is difficult to measure, because neither the clinician,
among attenders.94 Direct estimates of type 1 overdiagnosis for screened
pathologist, nor the patient can be sure whether the abnormality detected
U.S. females show marked differences depending on age of diagnosis,
by screening would be harmless or life threatening to the patient.
with less than 1% among premenopausal females and 22% among
Furthermore, overdiagnosis assumes that the level or amount of diagnosis
females aged 80 years.95
by symptomatic usual care is optimal. The estimates of overdiagnosis vary
widely between various studies (from almost none to up to 54%69,71,86-88) Prevention of cancer death is highly valued compared with false-positive
due to methods and parameters used for estimation and whether ductal results/overdiagnosis by most females.83 Current science cannot predict
MS-10

which breast cancer may be overdiagnosed or be potentially lethal in any screened females. To reduce mortality from breast cancer, yearly
one individual. Personalized treatment programs are recommended and screening is thought to be more beneficial. The panel also acknowledges
advances in personalized treatment will diminish the risk of overtreatment that incomplete compliance will alter the outcome of any recommendation.
and significance of overdiagnosis. The treatment of cancer may cause
suffering and anxiety, but that suffering is likely worth the gain from the An evaluation of the CISNET modeling of benefits of screening females
potential reduction in breast cancer mortality. According to the NCCN between 40 to 49 years found that using annual digital mammography
Panel, the risk of overdiagnosis and false positives are outweighed by the saves 30% more lives and 34% more life-years than biennial digital
benefit of mortality reduction in determining the age to recommend starting mammography.97 Also, with annual digital screening mammography, the
screening. deaths averted (0.6/1000) are similar for ages 40 to 44 and 45 to 49 years
(0.7/1000).96,98
The NCCN Panel emphasizes adopting strategies and research to reduce
the harms of screening (false positives and overdiagnosis) rather than A decline in breast cancer specific-mortality was observed in a cohort of
raising the age to initiate screening to potentially delay these issues. This females for every additional annual mammogram performed 5 years prior
includes newer imaging modalities that improve the detection of breast to breast cancer diagnosis; this further emphasizes the importance of
cancer with fewer recalls (eg, tomosynthesis). Research to better define annual mammography.99 The results of a primary analysis to estimate the
the biology of breast cancer is needed so that lesions that are not destined association between incidence of DCIS detected by screening and
to progress are either not treated or are treated less aggressively. subsequent invasive interval cancer incidence showed a DCIS detection
rate of 1.5 per 1000 screened and a reduction of one invasive interval
Screening Interval and Rationale for Annual Mammogram Screening: cancer per 1.5 to 3 DCIS cases detected.100
Another consideration is the time interval between screening exams.
Performing screening mammography annually versus every other year While the risk of false positives is greater with annual compared to biennial
remains controversial. Most studies and models suggest incremental mammograms,70 the panel believes that the lower mortality and morbidity
benefit with annual screening, especially among younger females and of annual screening outweighs this harm.
premenopausal females.69,70,80,96 The evaluation of benefits versus risk
Age to Stop Mammographic Screening:
strongly supports the value of screening and the importance of adhering to
Most trials for breast screening have used a cutoff age of 65 or 70
a schedule of regular mammograms.
years.101-103 However, observational studies and computer models show
mortality benefit to age 80 to 84.69,80 Considering the high incidence of
The NCCN Panel believes that the benefits of annual mammography
breast cancer in older individuals, the screening guidelines used for those
outweigh the risks. Breast cancer mortality is estimated to be lower with
≥40 years of age are recommended for all individuals age 40 and above
annual compared to biennial screening mammograms.80 Additionally,
with no age cutoff to stop screening. Clinicians should always use
mammograms can often detect a lesion 2 years before the lesion is
judgment when applying screening guidelines. The mortality benefit of
discovered by CBE. Interval cancer rates are lower among annually screening mammography is often delayed for 5 to 7 years in RCTs that
MS-11

emphasize the importance of life expectancy and overall health when cancer suggestive of a genetic predisposition, those with a prior history of
considering age to stop screening. Mammography screening should be thoracic radiation, or for those with LCIS.
individualized, weighing its potential benefits/risks in the context of the
patient’s overall health and estimated longevity.104 If a patient has severe The Gail model was updated using combined data from the Women’s
comorbid conditions limiting her expectancy and no intervention would Contraceptive and Reproductive Experiences (CARE) study and the
occur based on the screening findings, then the patient should not SEER database, as well as causes of death from the National Center for
undergo screening, regardless of age.104,105 Health Statistics, to provide a more accurate determination of risk for
African-American females.111 It has also been updated using the data from
Screening Recommendations for Individuals AFAB at the Asian American Breast Cancer Study (AABCS) and the SEER
Increased Risk of Breast Cancer database to provide a more accurate risk assessment for Asian and
Those with Prior History of Breast Cancer: These individuals are treated Pacific Islander females in the United States.112
according to the recommendations outlined in NCCN Guidelines for Breast
Increased risk of developing breast cancer is defined by the modified Gail
Cancer.
model for females ≥35 years of age as a 5-year risk of ≥1.7%. This is the
Those ≥35 Years of Age with a 5-Year Risk of Invasive Breast average risk for a 60-year-old female, which is the median age of
Carcinoma ≥1.7% by the Modified Gail Model: For those ≥35 years of diagnosis of breast cancer in the United States. The 5-year predicted risk
age, a risk assessment tool is available to identify those who are at of breast cancer required to enter the NSABP Breast Cancer Prevention
increased risk. The National Cancer Institute (NCI) and the National Trial of tamoxifen versus placebo, as well as the Study of Tamoxifen and
Surgical Adjuvant Breast and Bowel Project (NSABP) Biostatistics Center Raloxifene (STAR) trial, was ≥1.7%. As previously mentioned, the
has developed a computerized interactive risk-assessment tool based on modified Gail model risk assessment tool also provides an estimate of a
the modified Gail model106-110 that can be accessed at: female’s lifetime risk of breast cancer. However, this estimate is based on
http://www.cancer.gov/bcrisktool/Default.aspx, which provides risk the Gail model risk criteria, which differ from criteria used in risk
projections on the basis of several risk factors for breast cancer. The assessment models predominantly based on family history (see below).
modified Gail model assesses the risk of invasive breast cancer as a Lifetime breast cancer risk as determined by the Gail model is not used in
function of age, menarche, age at first live birth or nulliparity, number of these guidelines to determine whether an individual is eligible for
first-degree relatives with breast cancer, number of previous benign breast screening breast MRI.
biopsies, atypical hyperplasia in a previous breast biopsy, and race. The
For an individual AFAB ≥35 years of age with a 5-year risk ≥1.7%, the
model calculates 5-year and lifetime projected probabilities of developing
NCCN Panel encourages breast awareness and recommends a clinical
invasive breast cancer and can be used to identify those who are at
encounter every 6 to 12 months and annual digital mammography, with
increased risk. The Gail model should not be used for those with a
the consideration of tomosynthesis, to begin at the age identified as being
predisposing gene mutation, a strong family history of breast or ovarian
at increased risk by the Gail model. In addition, according to the NCCN
Panel, those in this group should be counseled for consideration of risk-
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reduction strategies in accordance with the NCCN Guidelines for Breast mutations. Strong genetic association between breast and ovarian cancer
Cancer Risk Reduction. has been demonstrated in some families by linkage analyses.
Those Who Have a Lifetime Risk >20% Based on History of LCIS or For those with a >20% lifetime risk of breast cancer based on models
ADH/ALH: A diagnosis of LCIS or ADH/ALH is associated with high risk of largely dependent on family history, the NCCN Panel encourages breast
development of cancer in either breast.113-118 awareness and clinical encounter every 6 to 12 months to begin at the
age identified as being at increased risk. The NCCN Panel recommends
For those with a history of LCIS or ADH/ALH, the NCCN Panel annual digital mammography, with the consideration of tomosynthesis
encourages breast awareness and recommends a clinical encounter every starting from 10 years prior to the youngest family member but not prior
6 to 12 months beginning at the age of diagnosis and annual digital to age 30. In addition, in accordance with the ACS guidelines,53 the NCCN
mammography, with the consideration of tomosynthesis, beginning at the Panel recommends annual breast MRI to begin 10 years prior to the
age of diagnosis of LCIS or ADH/ALH but not prior to age 30. In addition, youngest family member diagnosed but not prior to age 25 for those who
according to the NCCN Panel, annual MRI should be considered have a lifetime risk of breast cancer >20% based on models that rely
beginning at the age of diagnosis of LCIS or ADH/ALH but not before age mainly on family history. According to the NCCN Panel, individuals in this
25 (based on emerging evidence).55 Individuals in these groups should group should be asked to consider risk reduction strategies in accordance
also be considered for risk reduction strategies in accordance with the with the NCCN Guidelines for Breast Cancer Risk Reduction .
NCCN Guidelines for Breast Cancer Risk Reduction.
Those Who Have Received Prior Thoracic Irradiation Between the Ages
Those with a Lifetime Risk of Breast Cancer >20% Based on Models of 10 to 30 Years: Results from several studies have demonstrated that
Largely Dependent on Family History: A lifetime risk of breast cancer of females who received thoracic irradiation in their second or third decade of
>20% as assessed by models based largely on family history is another life have a substantially increased risk of developing breast cancer by age
risk threshold used in the guidelines to identify an individual as a potential 40 years.126-131 For example, in the Late Effects Study Group trial, the
candidate for risk reduction strategies, as well as to direct screening overall risk of breast cancer associated with prior thoracic irradiation at a
strategies. According to the ACS guidelines for breast screening, MRI may young age was found to be 56.7-fold (55.5-fold for female patients) greater
be performed as an adjunct to mammography53 in a female at high risk if than the risk of breast cancer in the general population.127,130 The RR of
the lifetime risk of breast cancer is approximately 20% or greater based on female breast cancer according to follow-up interval was 0 at 5 to 9 years;
models that rely mainly on family history. A cancer genetic professional 71.3 at 10 to 14 years; 90.8 at 15 to 19 years; 50.9 at 20 to 24 years; 41.2
should be involved in determining the lifetime risk of the individual based at 25 to 29 years; and 24.5 at >29 years.130 Results from a case-control
on models dependent on family history. These include Claus,119 study of females treated with thoracic radiation at a young age for Hodgkin
Tyrer-Cuzick,120 and other models.121-123 BRCAPRO124 and Breast and lymphoma indicated that the estimated cumulative absolute risk of breast
Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm cancer at 55 years of age was 29.0% (95% CI, 20.2%–40.1%) for a female
(BOADICEA)125 are more commonly used to estimate the risk of BRCA treated at 25 years of age with at least 40 Gy of radiation and no alkylating
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agents.132 Although there is a concern that the cumulative radiation The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast
exposure from mammography in a young female may itself pose a risk for and Ovarian include recommendations for referral to a cancer genetics
cancer, it is felt that the additional radiation in this population is negligible professional for further evaluation for individuals who have either a
compared to overall radiation exposure. Findings from a survey of breast personal history or a close family history meeting certain criteria and also
screening practices in this population of patients suggest that a sizable list screening recommendations for common hereditary syndromes that
segment of this group is not undergoing regular mammographic confer increased risk for breast and ovarian cancer. (See NCCN
screening.133 Guidelines for Genetic/Familial High-Risk Assessment: Breast and
Ovarian).
For those ≥25 years of age who have received prior thoracic irradiation,
the NCCN Panel recommends encouraging breast awareness, and Diagnostic Evaluation
recommends a clinical encounter be initiated every 6 to 12 months 10 Breast symptoms are common among individuals AFAB. A retrospective
years after radiation exposure.134 Breast imaging assessments with annual study of females aged 40 to 70 years showed that 16% (total visits of 23
digital mammograms, with the consideration of tomosynthesis, are per 100 females) of females will present with symptoms to their provider
recommended 10 years after RT but not prior to age 30, and annual during a decade with higher frequency among those ages 40 to 59 years
MRI44 is recommended to begin 10 years after radiation exposure but not compared to those who are older.135 Pain is found to be the most common
prior to age 25. symptom followed by palpable mass. In addition, palpable areas of
concern are identified during a breast physical exam. Breast clinical
For those <25 years of age who have received prior thoracic irradiation,
findings are not specific and there is variability in interpretation. Each
the NCCN Panel recommends encouraging breast awareness, counseling
symptom is associated with a risk of malignancy and warrants diagnostic
on risk, and an annual clinical encounter starting 10 years after radiation
evaluation; however, most symptoms will be determined to be benign in
therapy.
etiology. Those <40 years of age, who are not usually recommended for
Those with a Pedigree Suggestive Of or With a Known Genetic routine breast screening, also frequently present with breast symptoms.
Predisposition: Accurate family history information is needed to
Unlike imaging for screening, which is used to detect cancer in
adequately assess breast cancer risk. Familial cancers share some but
asymptomatic individuals, diagnostic evaluation is used to characterize a
not all features of hereditary cancers. For example, although familial
clinical finding or possible abnormality found during screening. There is
breast cancers occur in a given family more frequently than expected
confusion regarding the term “diagnostic” imaging, as it is applied to two
based on statistics, they generally do not exhibit inheritance patterns or
very different situations: 1) imaging for clinical finding such as a palpable
onset age consistent with hereditary cancers. Familial breast cancers may
mass; and 2) incremental imaging after a possible abnormal screening
be associated with chance clustering, genetic variations in
mammogram in an asymptomatic individual (also referred to as recall or
lower-penetrance genes, a shared environment, small family size, and/or
callback). To add further confusion, insurance carriers may consider a
other factors.
routine mammogram to be “diagnostic” in certain asymptomatic individuals
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(eg, in those with prior cancer). Diagnostic evaluation in this review will be The mammographic final assessments are mandated by the
restricted to the former two situations. Mammography Quality Standards Act and Program (MQSA) and are
reported using wording similar to the ACR BI-RADS® assessment
Diagnostic evaluation may include physical examination and diagnostic categories, which classify likelihood of the breast findings into 6 final
imaging for symptomatic individuals and diagnostic imaging for those assessment catergories.139 The BI-RADS® assessment categories (which
recalled from screening. Diagnostic imaging may include diagnostic include words and numbers) help to standardize both the reporting of
mammography, ultrasonography, and at times diagnostic breast MRI. The
mammographic findings and the recommendations for further
eventual decision regarding need for tissue sampling is based on level of management. The assessment wording and numbers are often used
suspicion on imaging and/or clinical examination. Biopsy is needed in
interchangeably. The definitions of the mammogram assessment
situations where imaging is negative but clinical findings are suspicious, categories are outlined in Mammographic Assessment Category
since imaging is not completely sensitive for cancer detection.
Definitions in the algorithm. Importantly, the same imaging terms are used
While the term “diagnostic” implies diagnosis, imaging results are often not for screened (asymptomatic) recalled individuals and symptomatic
specific enough to be truly “diagnostic.” individuals, which can create confusion regarding recommendations.
NCCN Recommendations for Screening Mammogram BI-RADS®

Diagnostic Imaging After Screening Mammography Recall
Assessment Categories 1, 2, 3, 4, 5, and 6 are listed below. The NCCN
Diagnostic Mammography
recommendations following evaluation of symptomatic diagnostic
Screening mammography consists of two standard x-ray images of each
individuals AFAB can be found in the next section. Importantly, Negative
breast, whereas a diagnostic mammogram includes additional views, such
or Benign BIRADS® imaging assessments, in the setting of symptoms,
as spot compression views or magnifications views, to investigate the
rely upon correlation of clinical finding, which may indicate need for
finding in question. Diagnostic mammography is associated with higher
biopsy even with negative imaging. Conversely, suspicious imaging
sensitivity but lower specificity as compared to screening mammography.
findings for those with clinical findings of very low suspicion still warrant
DBT may replace traditional diagnostic mammographic imaging in certain
biopsy.
situations.136-138
For BI-RADS® category 1 (negative finding) or category 2 (benign), the
Frequently, especially for masses or asymmetries, diagnostic ultrasound
panel recommends resuming routine screening.
is also performed. Each imaging modality may be positive or negative,
which allows four outcomes: both imaging modality results are negative; For BI-RADS® category 3 (probably benign), the panel recommends
both are positive; mammogram is positive and ultrasound is negative; diagnostic mammograms at 6 months, then every 6 to 12 months for 1 to 2
and mammogram is negative and ultrasound is positive. In general, a years as appropriate. If the lesion remains stable or resolves
“final” combined imaging assessment category is rendered after a “recall’ mammographically, the patient resumes routine screening intervals for
from screening, which is the most suspicious imaging outcome mammography. If, in any of the interval mammograms, the lesion
assessment. increases in size or changes its benign characteristics, a biopsy is then
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performed. The exception to this approach of short-term follow-up is when Diagnostic Breast MRI
a return visit is uncertain or the patient strongly desires or has a strong MRI can also play a role in the diagnostic setting. For patients with skin
family history of breast cancer. In those cases, initial biopsy with histologic changes consistent with serious breast disease, consideration of breast
sampling may be a reasonable option. MRI is included in the guidelines for those with benign biopsy of skin or
nipple following BI-RADS® category 1-3 assessment. Since a benign skin
For BI-RADS® categories 4 and 5 (suspicious or highly suggestive of
punch biopsy in a patient with a clinical suspicion of inflammatory breast
malignancy), tissue diagnosis using core needle biopsy (preferred) or
cancer (IBC) does not rule out malignancy, further evaluation is
needle localization excisional biopsy with specimen radiograph is
recommended. There is evidence that certain MRI features may facilitate
necessary. When a needle biopsy (aspiration or core needle biopsy) is
diagnosis of IBC.146 MRI may be used for suspicious nipple discharge
performed, concordance between the pathology report and the imaging
when mammography and ultrasound are not diagnostic.147-149
finding must be obtained.140,141 For example, a negative needle biopsy
associated with a spiculated category 5 mass (highly suggestive of Breast Tissue Biopsy
malignancy) is discordant and clearly would not be an acceptable
Breast biopsy is recommended if diagnostic imaging findings or clinical
diagnosis. When the pathology and the imaging are discordant, the breast
findings are suspicious (BI-RADS® 4) or highly suggestive of malignancy
imaging should be repeated and/or additional tissue sampled or excised;
(BI-RADS® 5).
surgical excision is recommended when pathology/image remains
discordant. Those with a benign result exhibiting pathology/image Fine-Needle Aspiration (FNA) Biopsy
concordance should be followed with mammography every 6 to 12 months An FNA biopsy involves use of a smaller-bore needle to obtain cytologic
for 1 to 2 years before returning to routine screening. samples from a breast mass. Advantages of FNA biopsy include its
minimally invasive methodology and low cost,150,151 whereas the need for
For BI-RADS® category 6 (proven malignancy), the patient should be
pathologists with specific expertise in the interpretation of test results and
treated according to the NCCN Guidelines for Breast Cancer.
the necessity of performing a follow-up tissue biopsy when atypia or
Breast Ultrasonography malignancy is identified are disadvantages of the procedure. FNA of
Imaging by ultrasound is an important adjunct for diagnosing breast nonpalpable lesions can be performed under imaging guidance (eg,
cancer.142 However, breast ultrasonography does not detect most ultrasound), although there is evidence to indicate that both core needle
microcalcifications.34,45,143-145 The definitions of the ultrasound assessment biopsy and excisional biopsy are more accurate than FNA in the
categories are outlined in Ultrasonographic Assessment Category evaluation of nonpalpable breast lesions.152,153
Definitions in the algorithm.
Core Needle Biopsy
A core needle biopsy, also called percutaneous core breast biopsy, is a
procedure that typically involves obtaining multiple cores of solid tissue
using standard techniques.154,155 It can be performed under imaging
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guidance (eg, stereotactic [mammographic] ultrasound or MRI) or directed may be needed. Excisional biopsy is recommended if the diagnosis by
by palpation. Advantages of breast core needle biopsy include: 1) core needle biopsy is an indeterminate lesion, a benign lesion that is not
increased accuracy over FNA when the procedure is performed in concordant with imaging, ADH or other specific histologies that require
situations where no mass is palpable; and 2) an ability to obtain tissue additional tissue including mucin-producing lesions, potential phyllodes
samples of sufficient size so as to eliminate the need for a follow-up tumor, papillary lesions, radial scars, or other histologies of concern to the
biopsy to confirm malignancy.156 In some situations, the core needle pathologist.151,156,161,162 Support for this recommendation includes results of
biopsy is performed under vacuum assistance, which can facilitate studies demonstrating an underestimation of cancer when atypical
collection of adequate tissue from a breast lesion without the need for hyperplasia and LCIS are diagnosed by core needle biopsy.163-168
multiple needle insertions.157-159 Marker clip placement is done at the time However, there are situations (eg, select cases of LCIS or ALH such as
of core needle biopsy so that the radiologist can identify the location of the those concordant with imaging, papillomas, fibroepithelial lesions, and
lesion in the event that it is entirely removed or disappears during radial scars) where close observation may be substituted for excisional
neoadjuvant treatment of a breast cancer.160 With a few exceptions, core biopsy in select patients.151,161,169-176
needle biopsy is preferred in the NCCN Guidelines over surgical excision
when tissue biopsy is required. Sensitivity for core needle biopsy directed Diagnostic Evaluation for Symptomatic Findings on Physical
by ultrasound or stereotaxis is 97% to 99%.98 According to the NCCN Examination
Panel, surgical excision is appropriate if unable to perform core needle In general, the breast imaging evaluations after physical exam include
biopsy. mammography and ultrasound. The addition of ultrasound to diagnostic
mammography significantly increases cancer detection and detection of
Excisional Biopsy
specific benign findings such as cysts. Imaging for females <30 years of
An excisional biopsy involves removal of the entire breast mass or
age begins with ultrasound, while those ≥30 years of age generally have
suspicious area of the breast by a surgeon in an operating room setting.
both studies unless a cyst is likely.177,178 ,179-182 Combined negative imaging
Needle or wire localization is done by the radiologist immediately prior to
results place a patient in a very low risk of malignancy (generally <3%)
an excisional biopsy of a nonpalpable mammographic or sonographic
category; however, clinical judgment is necessary as some females with
finding to direct surgical excision. The wire localization may bracket a
negative imaging may warrant biopsy that may identify a malignant
lesion that had a clip placed in it at the time of the core needle biopsy.160
mass.177,183-185 The recommendations for subsequent management follow
Newer localization methods using radionucleotide seeds, reflector devices,
imaging assessments and clinical level of suspicion. Imaging should
or magnetic devices are being explored.
precede biopsy in most situations due to potential alteration of imaging
Excisional biopsy is included in the NCCN Guidelines as an option when findings by the biopsy. BIRADS imaging assessments, even if negative,
tissue biopsy is required. Although excisional biopsy is a more invasive must be correlated with the clinical findings prior to final clinical
method than core needle biopsy and requires needle localization when recommendations and do not stand alone as in the screening situation.
lesions are not palpable, there are situations where larger tissue samples There are clinical situations where biopsy is warranted even with negative
imaging results.
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Symptomatic or positive findings on physical examination include palpable For those with mammographic findings that are suspicious or highly
mass in the breast, nipple discharge without a palpable mass, asymmetric suggestive of breast cancer, the NCCN Panel recommends ultrasound to
thickening or nodularity, skin changes, axillary mass, and breast pain. determine lesion size and to guide tissue biopsy. The NCCN Panel notes
that FNA and core needle biopsy are both valuable. However, FNA
Palpable Mass in the Breast requires cytologic expertise. When a needle biopsy is utilized,
A palpable mass is a discrete lesion that can be readily identified during a concordance between pathology, imaging, and clinical findings must be
physical exam. The NCCN Guidelines separate the evaluation of obtained.
individuals AFAB with the palpable mass into two age groups: those ≥30
years of age and those <30 years of age. Ultrasound Findings:
Solid Mass:
Those with Palpable Mass ≥30 Years of Age: If the solid mass found on the ultrasound is suspected to be probably
The main difference in the guidelines for evaluating a palpable mass in benign (ie, BI-RADS® category 3), the options are: 1) observation, if
those ≥30 years of age compared with those <30 years of age is the clinical suspicion for breast cancer is low; or 2) tissue (core needle)
increased degree of suspicion of breast cancer. The initial evaluation biopsy, if the mass is clinically suspicious. Observation may be elected for
begins with a diagnostic mammogram and ultrasound. Ultrasound should those with low clinical suspicion; a physical examination follow-up with or
be geographically correlated with the palpable mass in question. without ultrasound or diagnostic mammogram is recommended every 6
Observation without further evaluation is not an option for these months for 1 to 2 years to assess stability of the solid mass. There may be
individuals. There are some clinical circumstances, such as mass with variability on the follow-up interval based on the level of suspicion.
low clinical suspicion or suspected simple cyst, in which ultrasound Numerous clinical studies now support the ability of ultrasound to
would be preferred and may suffice for those 30 to 39 years of age due accurately characterize palpable solid masses as probably benign with
to the high sensitivity of ultrasound alone. 180,181,186 After the diagnostic risk of malignancy generally <2%. However, these same studies have
imaging assessment, the abnormality is placed into one of the following shown that many such masses will eventually warrant biopsy and
categories: negative or benign; probably benign; or suspicious or highly compliance with follow-up may be low.178,180,187-191 Progression of size or
suggestive of cancer with management following BIRADS final suspicion on follow-up studies warrants tissue biopsy. The NCCN Panel
assessment recommendations. recommends a tissue (core needle) biopsy for solid masses with a
BI-RADS® 4-5.
If there is a lack of geographic correlation between clinical and imaging
findings, further evaluation is recommended. Sensitivity of combined
mammography and ultrasound for evaluation of palpable masses is high Cystic Masses:
for cancer detection, although specificity may be relatively low. Breast cysts are classified as simple, complicated, or complex based on
the characteristics identified by ultrasound evaluation (see Table 1 for
definitions).
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Simple Cyst value of negative imaging is high, >96%.177,181,184 Soo, 2001 #674,185 If the clinical
A cyst meeting all criteria of a simple cyst is considered to be benign (ie, lesion increases in size or suspicion, tissue biopsy should be performed,
BI-RADS® 2)34,192 if the clinical findings and ultrasonographic results are whereas routine breast screening is recommended if the lesion remains
concordant. In a retrospective analysis of females (n = 14,602) with stable.
benign breast biopsies developing subsequent breast cancer, it was
Follow-up after Core Needle Biopsy
noted that simple cysts were not associated with subsequent breast
If the biopsy result indicates benign mass, and this finding is concordant
cancer development. 193 Therefore, these patients then can be followed
with the imaging results, the NCCN Panel recommends either routine
with routine screening.
screening or a physical examination at 6 or 12 months, with or without
Complicated Cyst ultrasound or mammogram, for 1 year to ensure that the lesion is stable.
A complicated cyst is associated with a low risk of malignancy (<2%) Routine breast screening is recommended if the lesion is stable. If the
(BI-RADS® 3).34,194-196 Options for managing complicated cysts are either lesion increases in size, the NCCN Panel recommends surgical excision.
aspiration or short-term follow-up with physical examination and
ultrasonography with or without mammography every 6 to 12 months for 1 If the diagnosis by tissue biopsy is an indeterminate lesion, a benign lesion
to 2 years to assess stability. There may be variability on the follow-up that is not concordant with the imaging findings, or ADH, the NCCN Panel
interval based on the level of suspicion. Complicated cysts that increase in recommends surgical excision. Mucin-producing lesions, potential
size or suspicion should be biopsied. Those that are stable or confirmed to phyllodes tumor, papillary lesions, radial scars, or other histologies of
be a complicated cyst with visible mobility of internal components can be concern to the pathologist may also require excisional biopsy. Select
followed with routine screening. patients (ie, some patients with flat epithelial atypia, papillomas,
fibroepithelial lesions, radial scars) may be suitable for monitoring in lieu of
Complex (Cystic and Solid) Mass: surgical excision. For patients with classic LCIS or ALH that is concordant
A complex cystic and solid mass has both cystic and solid components. with imaging, the NCCN Panel recommends physical exam with or without
Complex cysts have a relatively high risk of malignancy (eg, 14% and 23% imaging for 6 to 12 months along with risk reduction therapy according to
in 2 studies).34,162,195-197 The NCCN Panel recommends a tissue (core the NCCN Guidelines for Breast Cancer Risk Reduction or surgical
needle) biopsy for complex (cystic and solid) masses (BI-RADS® 4-5). excision. Multiple-foci LCIS involving greater than 4 terminal ductal units
on core biopsy is associated with increased risk of being invasive
No Imaging Abnormality: cancer.174 Patients with pleomorphic LCIS or LCIS/ALH that is non-
If no ultrasonographic or mammographic abnormality is detected concordant with imaging are treated with surgical excision.
(BI-RADS®) 1), tissue biopsy (core needle biopsy) should be carried out
for suspicious clinical findings; and 2) those with low clinical suspicion Any malignant findings with biopsy or surgical excision should be treated
observation with or without mammogram and ultrasound should be according to the NCCN Guidelines for Breast Cancer.
considered for 1 to 2 years to assess stability. The negative predictive
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Those with Palpable Mass <30 Years of Age: pregnancy, following breast stimulation, in females with certain thyroid
The preferred option for initial evaluation of a palpable mass is to conditions, and in those taking certain medications, such as estrogen, oral
proceed directly to ultrasound. 180 Mammogram may be considered if contraceptives, opiates, and particular antihypertensive agents.198
ultrasound or CBE results are highly suspicious or suggestive of cancer
or if the patient is identified as having a high risk for breast cancer based Suspicion of underlying pathology (eg, ductal carcinoma, papilloma) is
on personal and family history. From this point, the decision tree for raised when nipple discharge is persistent and reproducible on
those <30 years of age is almost identical to the pathway for those ≥30 examination, spontaneous, unilateral, from a single duct, serous,
years of age. The main difference is consideration of a diagnostic sanguineous, or serosanguineous.205
mammogram in only some situations for those <30 years of age.
In patients with a nipple discharge but no palpable mass, an evaluation of
Because the incidence of malignancy in those <30 years of age is low,
the characteristics of the nipple discharge is the first step. The appropriate
observation of the mass for one or two menstrual cycles is also an option
follow-up of a non-spontaneous, multiple-duct discharge in individuals
in cases with low clinical suspicion. If observation is elected and the
AFAB <40 years of age is observation, coupled with education to stop
mass resolves or is stable after one or two menstrual cycles, the patient
compression of the breast and to report the development of any
may return to routine care. If there is significant increase in size or
spontaneous discharge. In those ≥40 years of age, mammography and a
increase in clinical suspicion, ultrasound should be performed. Needle
further workup based on the BI-RADS® category along with education
sampling prior to imaging is not recommended.
similar to that for those <40 years of age is recommended. Evaluation of
this type of nipple discharge is based on the overall BI-RADS® category of
If no ultrasonographic abnormality is found (negative, BI-RADS® 1), a
the diagnostic mammogram, if not done previously.
mammogram is recommended in cases where there is clinical suspicion.
Based on the mammogram results, from this point the management is Patients presenting with no palpable mass but with persistent,
identical to the pathway for those ≥30 years of age. If the clinical spontaneous, unilateral, single-duct, and clear or bloody discharge are
suspicion is low, physical examination every 3 to 6 months for 1 to 2 imaged with age-appropriate diagnostic mammography and ultrasound.
years is recommended with or without ultrasound. If the mass increases Several clinical studies have established a very low risk of malignancy
in size during the observation period, diagnostic mammogram may be when these tests are negative.206,207 In certain situations, MRI or
considered followed by tissue (core needle) biopsy. If the mass remains ductogram may play an adjunctive role, aiding in identifying a possible
stable, routine breast care is recommended. abnormality and its location. Several studies have shown that breast MRI
aids in the diagnosis of suspected ductal disease.147-149,208,209
Nipple Discharge Without a Palpable Mass
According to the NCCN Panel, when an overall imaging BI-RADS®
Nipple discharge is common, and, in many cases, unrelated to breast assessment is category 1-3 (negative, benign, or probably benign), either
pathology.198-204 For example, non-spontaneous discharge from multiple a ductogram or MRI are optional to guide the duct excision. The
breast ducts in an individual that is not lactating can occur during management options include duct excision210 or follow-up with physical
MS-20

exam after 6 months and imaging with diagnostic mammogram with or findings indicate progression, it should be investigated as previously
without ultrasound for 1 to 2 years. If clinical suspicion increases during described for palpable mass.
follow-up, tissue biopsy is recommended.
If a clinically suspicious change is noted or the overall imaging findings are
®
For BI-RADS category 4 or 5 (suspicious or highly suggestive of classified as BI-RADS® assessment category 4-5 (suspicious or highly
malignancy), the NCCN Panel recommends a tissue biopsy. If the biopsy suggestive of malignancy), a tissue biopsy is recommended.
findings are benign, a ductogram is optional, but surgical duct excision
would still be necessary. If findings are indicative of malignancy, the Skin Changes
patient should be treated according to the NCCN Guidelines for Breast Any type of unusual skin changes around the breast may represent
Cancer. serious disease and needs evaluation. IBC should be considered when
dermal edema (peau d’orange) and breast erythema are present, and
Asymmetric Thickening or Nodularity nipple excoriation, scaling, and eczema should increase clinical suspicion
Thickening, nodularity, or asymmetry is distinct from a palpable mass in of Paget’s disease. IBC is a rare, aggressive form of breast cancer
that the finding is ill-defined and often vague on physical breast estimated to account for 1% to 6% of breast cancer cases in the United
examination. Factors to consider include whether the thickening is a new States. IBC is a clinical diagnosis that requires erythema and dermal
or previous finding, and whether or not it appears to be representative of edema of a third or more of the skin of the breast with a palpable border to
normal asymmetry. Imaging evaluation follows that of a palpable mass.177 the erythema.211,212 Paget’s disease of the breast is a rare manifestation of
If the patient is <30 years of age and has no high risk factors, ultrasound breast cancer characterized by neoplastic cells in the epidermis of the
evaluation is appropriate followed by consideration of diagnostic nipple areolar complex. It most commonly presents with eczema of the
mammography. Diagnostic mammograms for this age group are low in nipple or areola, bleeding, ulceration, and itching of the nipple. The
yield because of the density of the breast and low risk of breast cancer. In diagnosis is often delayed because of the rare nature of the condition and
those ≥30 years of age, a diagnostic mammogram and an ultrasound confusion with other dermatologic conditions.213,214 Pure Paget’s disease is
evaluation should be obtained. frequently occult on mammography215 and a negative mammogram does
not exclude Paget’s disease, which requires skin biopsy.
If the overall imaging findings are classified as BI-RADS® category 1-3
(negative, benign, or probably benign) and the clinical assessment is The initial evaluation of a patient with breast skin changes begins with a
benign, the patient should be clinically reexamined with imaging as bilateral diagnostic mammogram with or without ultrasound imaging. If the
needed in 3 to 6 months to assess stability. Age-appropriate diagnostic imaging results are abnormal, the evaluation proceeds based on the
mammogram and/or ultrasound may be performed every 6 to 12 months imaging findings. If the breast imaging results are normal, further workup
for 1 to 2 years to assess stability. If the findings on physical exam and/or is still needed.
imaging are stable, routine screening can be resumed. If either or both
Punch biopsy of the skin or nipple biopsy should be performed following
imaging findings consistent with an overall BI-RADS® assessment
MS-21

category 1-3 (negative, benign, or probably benign). Antibiotics may or NCCN Panel recommends providing reassurance to the patient and
may not be given, depending on the clinical suspicion for breast infection, treating the pain with symptomatic management (eg, over-the-counter pain
but should not delay diagnostic evaluation. If biopsy results are benign, medications, if needed; use of a good support bra; ice packs or heating
clinical and pathologic correlation should be reassessed. In addition, a pads). Cyclical breast pain may often spontaneously resolve.
breast MRI, a repeat biopsy, and consultation with a breast specialist Reassurance alone has shown to help resolve the symptom in 86% of
should be considered. If the skin biopsy is malignant, the patient should be women with mild pain and in 52% of women with severe pain.218 If the
treated according to the NCCN Guidelines for Breast Cancer. breast pain is focal in nature, the NCCN Panel recommends age-
appropriate diagnostic imaging (diagnostic mammogram with or without
A tissue biopsy should be performed if imaging findings are consistent of ultrasound for those ≥30 years of age; and ultrasound for those <30 years
an overall BI-RADS® assessment category 4-5 (suspicious or highly of age).
suggestive of malignancy). According to the NCCN Panel, core needle
biopsy is the preferred option with or without punch biopsy, although For those with BI-RADS® assessment category 1 (negative findings), the
surgical excision is also an option. A benign biopsy result should be panel recommends appropriate symptom management of breast pain. For
followed by a punch biopsy of the skin, if not previously performed, or a simple cyst (benign or BI-RADS® assessment category 2) geographically
nipple biopsy, with reassessment as described above for BI-RADS® correlated with focal pain, drainage may be considered for symptom relief.
category 1-3. A biopsy showing a malignant finding should be managed For complicated cysts (probably benign or BIRADS 3), the panel
according to the NCCN Guidelines for Breast Cancer. recommends appropriate imaging every 6 months for 1 to 2 years along
with symptomatic management of the breast pain, if desired. A tissue
Breast Pain (core needle) biopsy should be performed if imaging findings are
Breast pain is the most common symptom in the breast. Individuals consistent of an overall BI-RADS® assessment category 4-5 (suspicious or
presenting with breast pain fear that this is a symptom of breast cancer, highly suggestive of malignancy).
therefore causing significant anxiety. The risk of cancer in a female
presenting with breast pain as the only symptom is low, between 1.2% and Axillary Mass
6.7%.6,135,216,217 Localized axillary masses are more often related to benign disorders than
malignancy.219 Masses may relate to axillary lymph nodes, accessory
breast tissue in the axilla, or other soft tissue abnormality. Infections,
Evaluation of persistent and severe breast pain includes comprehensive
inflammation, and malignancy can cause lymphadenopathy. Breast
history, type of pain, relationship to menses, duration, location, impact on
implants can also cause benign axillary lymphadenopathy.220 However,
activities of daily living, factors that aggravate/alleviate pain, any other
when cancer is identified in the axillary lymph nodes, breast cancer is the
medical problems and comorbidities, and a thorough CBE. If CBE fails to
most common cause of axillary lymphadenopathy. In a study evaluating 31
identify any physical abnormality such as palpable mass, asymmetric
patients with isolated axillary masses, 9 of the 17 cases with cancer had
thickening, nipple discharge, or skin changes; the pain is cyclic; or diffuse
occult breast cancer (5 in the contralateral breast) 221
and non-focal and screening mammograms are current and negative, the
MS-22

For an individual presenting with unilateral or bilateral localized axillary

mass and no signs of lymphoma, the NCCN Panel recommends complete
clinical evaluation to assess for other sites of adenopathy and potential
non-breast etiologies of adenopathy. If no systemic disease is found, the
NCCN Panel recommends age-appropriate diagnostic imaging (ultrasound
with mammogram for those ≥30 years of age; and ultrasound for those
<30 years of age). Palpable axillary mass with negative/benign imaging
results should be clinically managed, as appropriate depending on level of
clinical suspicion. A core needle biopsy is recommended for palpable
axillary mass that is suspicious or highly suggestive on imaging. However,
suspicion of lymphoma in axillary lymph nodes may require special
pathologic evaluation and/or surgical excision of the axillary mass.
If the core needle biopsy results indicate malignancy of breast origin in the
axillary lymph node but no breast abnormality is evident with ultrasound or
mammogram, the panel recommends performing MRI and then following
the NCCN Guidelines for Breast Cancer as needed for management of the
axillary mass. For malignant axillary node with confirmed malignant breast
mass or for other types of malignant axillary lymph nodes, the panel
recommends referring to the appropriate NCCN Guidelines for
management.
Summary
The intent of the NCCN Guidelines for Breast Cancer Screening and
Diagnosis is to give health care providers a practical, consistent
framework for screening and evaluating a spectrum of clinical breast
lesions. Clinical judgment should always be an important component of
the optimal management of the patient.
MS-23

Table 1: Breast Cysts - Types and Definitions
Simple Anechoic (cystic), well-circumscribed,

round, or oval with well-defined
imperceptible wall and posterior
enhancement.
Complicated Has most but not all elements of a simple

cyst. Complicated cysts do not contain
solid elements, intracystic masses, thick
walls, or thick septa. This type of cyst may
contain low-level echoes or intracystic
debris, and can be described as a round,
circumscribed mass containing low-level
echoes without vascular flow, fulfilling
most but not all criteria of a simple cyst.
Complex Has some discrete solid component,

which may include thick walls, thick septa,
and/or intracystic mass. Complex cysts
have both anechoic (cystic) and echogenic
(solid) components.
151,162,192,194-197,222
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NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

*Therese B. Bevers, MD/Chair Þ Jeffrey Hawley, MD ф Liane Philpotts, MD ф

NCCN Bhavika K. Patel, MD ф ф Diagnostic/Interventional ₪ Medical genetics/

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

SCREENING OR SYMPTOM CATEGORYa SCREENING/FOLLOW-UPb

• Clinical encounterb,d,k every 1–3 y

Average • Annual clinical encounterb,d,k

Symptomatic Presenting Signs/Symptoms (BSCR-5)

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

SCREENING OR SYMPTOM CATEGORYa SCREENING/FOLLOW-UP

Increased Risk: • Clinical encounterb,d,k every 6–12 mo

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

SCREENING OR SYMPTOM CATEGORYa SCREENING/FOLLOW-UP

• Annual clinical encounterb,d,k

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

SCREENING OR SYMPTOM SCREENING/FOLLOW-UP

• Clinical encounterb,d,k every 6–12 mo

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

PRESENTING SIGNS/SYMPTOMS DIAGNOSTIC

Acquired/new onset nipple

Axillary mass(es) (See BSCR-13)

w Individualswith breast implants have a very small risk of developing BIA-ALCL

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

PRESENTING DIAGNOSTIC IMAGING FINDINGS FOLLOW-UP

• BI-RADS category 1 (negative)

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

IMAGING FINDINGS WITH PALPABLE SYMPTOMv,y FOLLOW-UP

If low clinical suspicionff: Stable or Screeninggg

ee Aspiration may be considered for symptomatic relief or possible abscess.

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

MANAGEMENT OF NIPPLE INVERSION/RETRACTION

Congenital/ If recent changes

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

PRESENTING DIAGNOSTIC EVALUATION AND FOLLOW-UP FOLLOW-UP

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

PRESENTING SIGNS/SYMPTOMS DIAGNOSTIC EVALUATION AND FOLLOW-UP

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

PRESENTING SIGNS AND SYMPTOMS FOLLOW-UP EVALUATION

Palpable symptoms See BSCR-6

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index

IMAGING FINDINGS FOR FOCAL BREAST PAIN FOLLOW-UP EVALUATION

BI-RADS Symptomatic management