Breast disease

Learning objectives
Basic science
Describe how breast anatomy relates to clinical findings
and malignant metastases.
Epidemiology
Discuss risk factors for malignant breast disease
Give at least four differentials for a benign breast mass.
List at least three types of malignant breast mass.
Signs and symptoms
List the clinical features of a malignant breast mass .
Special attention should be paid to the risk factors, clinical
characteristics and investigation of:
Fibroadenoma
Ductal carcinoma
Pagets disease of the breast
Diagnosis and management
Discuss the investigation, of a breast mass including the
pathological and radiologic findings.
Describe prognostic factors including receptor positive
status and discuss how receptor status can influence
treatment

Gross anatomy
Breast lies within superficial fascia
Suspensory ligament of cooper attach nipple
and skin to breast.
Posterior suspensory ligament lies in retro
mammary area, separates mammary tissue from
underlying pectoral fascia
Internal thoracic, axillary and intercostal arteries.

Note: Fibrous bands extend from the dermis into the breast and form
bands of cooper. These attach skin and nipple to the breast. distortion
or contraction of this ligament by parenchymal lesions may be
manifested by skin dimpling or nipple retraction. Posterior suspensory
ligamant is extension of superficial fascia which fills mammary space.
Breast tissue lies in this post susp lig, in cancer the breast gets fixed to
the chest wall by cancer spreading across the post susp lig into the

pect muscle. Arterial supply subject to much variation but usually

internal thoracic vessels supply majority of blood.
Venous drainage is more variable, but can drain pretty directly to
vertebral veins through deep venous drainage into the intercostal
veins. hence cancer goes to vertebrae.
Lobar architecture
Functional lobular architecture 15-25 lobes,
Each lobe is parenchyma associated with a
major lactiferous duct ending at the nipple
Lactiferous duct lined by squamous and then
glandular epithelium
Squamocolumnar junction important in some
carcinomas ( pagets)
Myoepithelial and basel cells also present in ducts

Note: The existence of functional lobar architecture provides anatomic

framework for treating some benign conditions by major duct excision
and certain types of cancer by quadranectomy.
Volume drained by duct and length of duct highly variable
Superficial portion of duct is lined by squamous epithelium
Basel cells thought to be capable of differentiating into columnar or
myoepithelial cells
Nipple
Nipple covered by stratified squamous epithelium.
Nipple surrounded by areolar area with Montgomery glands
Pigmented
Note: Each lactiferous duct terminates in and exits from the nipple.
Montgomery glands moisten the nipple and areolar skin, atrophy after
menopause.
Hyper pigmented states show in nipple eg pregnancy, Addisons
Lymphatics
Axillary lymph nodes receive >75% of the lymph drainage from the
breast and the rest flows into the parasternal (internal
mammary)group of lymph nodes.

Noncancerous Conditions
Benign masses
Fibrocystic changes
Cysts:
Fibroadenomas:
Phyloides tumour
Infections:
Trauma
gynecomastia
Benign Masses Fibrocystic changes
Lumpiness, thickening and swelling, often associated
with a womans period
Aberration of normal cyclical changes
Commonest 40-60yrs
Epithelial hyperplasia(adenosis), fibrosis, and cystic changes with
apocrine cells
Not related to OCP/HRT
Diffuse lumpiness which may be painful

Note: Benign mammary dysplasia, epitheliosis, adenosis, fibroadenosis

Often hx of painful breast premenstrually.
Need to exclude cancer in lumps
Cysts lines by apocrine clees

Benign Masses Breast cysts

Fluid-filled lumps can range from very tiny to about the size of an
egg
Breast acini coalesce to form cyst
Any age pre-menopause
Breast lump+/- pain
Often PMHx of cysts
Exclude malignancy
Aspirate
galactocoele
**Ultra sound to differentiate benign cystic
from solid mass
Note: May be any size, single or multiple
Not associated with skin changes or tethering
Refer if aspiration fluid blood stained or cyst recurs >2x
Exclude malignancy if no PMHx
Galctocoele is milk containing cyst which occurs during pregnancy.
Refer any new lump during pregnancy to a surgeon.

Benign Masses Fibroadenoma

Most common benign breast mass in age < 35 years
May increase in size with increased estrogen (pregnancy)
Small, firm or rubbery , mobile mass with sharp border, non
tender
Pathology: encapsulated, abundant stroma and normal
cellular elements
Treatment surgical excision

Mammography: oval density with smooth margins, pop corn

calcifications seen with degenerating fibroadenoma

Benign Masses Phylloides tumors

Women in their 40s - 50s
Arises from fibro epithelial cells similar to fibroadenoma, with
overgrowth of periductal stromal cells
Rapidly growing large bulky benign tumor, painless mobile mass,
may recur following excision
5 10% undergo malignant degeneration
Ultrasound: large smooth multilobulated mass
Pathology: cystic spaces in stroma causing leaflike (phyllodes)
appearance
Treatment: Simple excision
Firm wooden-log consistency
involving almost the whole breast with well
circumscribed collateral bluish veins on the skin

Breast abscess

Lactating breast or mammary duct ectasia

Gradual onset of pain
Hot, tender swelling
Refer for surgical drainage
Parenchymal scarring can cause overlying

skin changes
Mastitis

Note: Usually in lactating breast after mastitis

Indrawn nipples can also predispose to abscess
Pain in one breast segment

Fat necrosis

A blow to the breast or a bruise can cause a lump

Saponification of fat cells
Tender
Hx of trauma
Disrupted fat cells become surrounded
by lipid-laden macrophages, multinucleated
giant cells, and acute inflammatory cells.
May show abnormality on mammogram

Gynecomastia
Enlarged breast in males
Usually does not predispose to cancer of the breast except in
Klinefelter syndrome
Physiological gynecomastia(excess estrogen): neonates,
adolescence, old age
Excess estrogen: testicular tumors, cirrhosis of liver
Androgen deficiency: Klinefelter syndrome (XXY)
Drugs: estrogens,anabolic steroids, marijuana, spironolactone,
digitalis, cimetidine, ketoconazole, alcohol

Breast cancer
#1 site of new cancers in women
#2 site of cancer deaths in women
1:8 risk of developing breast cancer during the lifetime of a
woman
Women diagnosed with breast cancer in 2010 have an 89%
chance of being cured of the disease
Breast cancer Risk Factors

Female sex
Increasing age
Family history
Personal history of breast cancer
Biopsy confirmed benign breast disease (especially atypical
ductal hyperplasia)
Hormonal factors early age at menarche or late menopause,
late age at first pregnancy(after 30), nulliparity, prolonged
postmenopausal estrogen use
Prior radiation therapy to breast
High fat content in diet, obesity
h/o endometrial or ovarian cancer
Breast cancer Genetic basis of breast cancer

5% - 10% of all cases of breast cancer in United States

BRCA1 and BRCA2, PTEN(with Cowden disease), p53 (with LiFraumeni syndrome), STK11(with Peutz Jeghers syndrome)
Breast cancer risk in women with abnormal genetic screen is
50% - 80%
Biomarkers of breast cancer aggressiveness
-HER2 GENE AND PROTEIN
90 percent of women have no family history of breast cancer

Breast cancer General principles

Left breast>right
10% bilateral

 Upper outer quadrant 50%

Ductal carcinoma most common(75%)-In situ and
invasive(beyond basement membrane)
Lobular carcinoma(10%) - tend to be bilateral and multiple,
orderly rows of cells-In situ and invasive
Cancers can be infiltrating or non infiltrating ( in situ)
Note: Infiltrating have penetrated beyond basement membrane in situ,
non invasive cancer has best prognosis ( not surprisingly!)

Breast cancer Types

Ductal carcinoma- atypia in cells with cribriform pattern
Lobular carcinoma- indian file of cells
Pagets carcinoma
infiltrating ductal carcinoma in the nipple , eczematous
lesion in nipple, presence of Paget cell large nuclei with
pale staining cytoplasm
Inflammatory carcinoma
most aggressive lesion, diffuse induration, erythema and
edema, peau dorange due to dermal lymphatic
involvement, 50% survival in 5 years
Medullary carcinoma
fleshy, cellular, plasma cell and lymphocytic infiltrate, good
prognosis

Ductal carcinoma

Note: Different types depending on cell lay out,

mitotic centers, tendency to form tubular structures
etc.
CRIBIFORM
Lobular carcinoma

Arise from terminal ductules

of the lobule
Often multicentric and bilateral (20%)
Characteristic "Indian file" strands of
infiltrating lobular carcinoma cells are
seen in the fibrous stroma

Pagets disease of the breast

Asubtypeofductalcarcinomawithlarge,

malignantcellsofglandularorigin(pagetscells)
whichspreadsoutoftheductsoverthenipple.
Eczematoustypeskinchange.
Pagetscellsinfiltrateandproliferateintheepidermis,
causingthickeningofthenippleandtheareolarskin.
Thesetumorousepithelialcellsarederivedfromluminal
lactiferousductalepitheliumofthebreasttissue

Note: There is an underlying infiltrating ductal

carcinoma
Inflammatory breast cancer
Most aggressive lesion, with diffuse
induration, erythema and edema,
peau dorange due to dermal
lymphatic involvement,
50% survival in 5 years

Abnormal signs and symptoms

Change in breast size
Pain or tenderness
Redness
Change in nipple position
Scaling around nipples

 Sore on breast that does not heal

Note: A recent change in breast size, especially unilaterally can be of

concern if not related to a normal physiological change.
Breast pain or tenderness during the menstrual period is normal.
However, prolonged tenderness may be a sign of breast cancer. It is
important to note that most malignant breast lesions are not painful.
Inflammatory signs of cancer can be rash or edema.
A change in the direction the nipple is pointing may also be a sign of
breast cancer.
Scaling on nipples can also indicate a problem. Scaling around both
nipples could be due to allergy to soap or powder but scaling around
one nipple often indicates an abnormality.
And then finally a sore on the breast that does not heal should be
examined by a physician.

Abnormal Signs(breast tumors)

Puckering
Dimpling(peu dorange)
Nipple Retraction
Nipple discharge
Thickening of skin or lump or knot
Note:

So, lets look at abnormal signs and symptoms.

Breast tumors can produce puckering, dimpling, or retractions
by disrupting underlying structures. Also, if a tumor is blocking
the lymphatic drainage, the pores of the breast skin may become
more prominent. This results in an orange peel appearance.
In breast self-exam, the nipple should always be squeezed to check
for discharge. Any new discharge should be reported to the physician.
A milky or clear discharge can be a normal finding in women anytime
following childbirth. Greenish discharges are often a sign of mastitis

and infection. A bloody discharge is strongly suggestive of breast

cancer and should be reported immediately.
Any new thickening of the skin or lump or knot in the breast should
be reported to a physician. It is normal for an adult breast to feel
granular, nodular, or lumpy especially premenstrually. However, any
new mass or enlargement of an existing mass should be reported to a
physician. Breast cancers tend to be hard, with no clear borders and
immobile ( attached to skin or underlying structures).
A retracted or inverted nipple can be normal and in itself is not a
problem. However the recent inversion of a nipple could be a sign of
breast cancer.

Most common:
lump or
thickening in
breast. Often
painless
Redness or pitting of skin
Discharge

over the breast, like the

or bleeding

skin of an orange

Change in size or

Breast
Examination

Change in color or

cancer

contours of breast
appearance of areola
Axillary lymph node involvement is single most important
prognostic factor
Pathology: atypia in cells with cribriform pattern, desmoplastic
stroma and stellate morphology in infiltrating ductal carcinoma
Mammogram

cancer

Staging and treatment of breast

Sentinel node dissection is the preferred method for staging for

axillary lymph node involvement

 Early invasive breast cancer (cancer restricted in breast or

involved axillary lymph nodes are mobile) modified radical
mastectomy or lumpectomy with sentinel node with radiation,
chemotherapy if node positive cancers, Tamoxifen if estrogen
receptors positive
Advanced breast cancer (involved axillary lymph nodes are
fixed or distant metastases) Neoadjuvant systemic therapy for
locally advanced cancer followed by mastectomy. Hormonal
therapy for distant metastases

Lymphoedema
A Complication of surgery

Treatment Chemotherapy
Chemotherapy - various regimes eg CMF, response rate 40-60%,
median duration 8 months, taxel improving response
Adjuvant systemic treatment Tamoxifen for E2 and
progesterone receptor positive disease, recently aromatase
inhibitors.
Monoclonal antibodies trastuzmab (herceptin) for HER2 positive
High risk women need adjuvant chemotherapy +/- ovarian
ablation
Note: HER2 is a transmembrane tyrosine kinase receptor and a
member of the ErbB protein family, more commonly known as the
epidermal growth factor receptor (EGFR) family. Activation of this class
of cellular receptors is known to result in increased activity of a variety
of molecular pathways associated with tumor growth and progression.
HER2 is overexpressed in 18-20% of invasive breast cancers, which has
both prognostic and predictive implications. Before the routine use of
trastuzumab (Herceptin, a monoclonal antibody) in adjuvant therapy,
HER2 overexpression was associated with a more aggressive tumor
phenotype and worse prognosis (higher rate of recurrence and
mortality), independent of other clinical features (eg, age, stage, tumor

grade), especially in patients who did not receive adjuvant

chemotherapy.
Additionally, HER2 status has been shown to be predictive for response
to certain chemotherapeutic agents (ie, doxorubicin [Adriamycin]; and
HER2-targeted therapies trastuzumab and lapatinib [Tykerb, a smallmolecule oral tyrosine kinase inhibitor directed specifically to the HER2
receptor]).
Excision can be wide local with breast conservation or mastectomy
with reconstruction. Radiotherapy used with wide local to decrease
chance of local reccurrence
Taxel containing regimens good for relapse eg paclitaxel or docetaxel
Radiotherapy reduces local recurrence by 25% and improves survival
by 3%
Tamoxifen reduced mortality by 25%
Cyclophosphamide, methotrexate fluoruracil

Poor prognostic factors

Young age
Pre-menopausal
Tumour size
High grade tumour
Oestrogen and progesterone receptor negative
HER2 negative
Positive nodes

Note:

HER2 is a transmembrane tyrosine kinase receptor and a

member of the ErbB protein family, more commonly known as the
epidermal growth factor receptor (EGFR) family. Activation of this class
of cellular receptors is known to result in increased activity of a variety
of molecular pathways associated with tumor growth and progression.

Breast cancer Screening

Clinical exam by MD or nurse

Performed by doctor or trained nurse
practitioner

 Annually for women over 40

At least every 3 years for women between
20 and 40
More frequent examination for high risk
patients
Mammography X-ray of the breast
Has been shown to save lives in patients 5069*
Data mixed on usefulness for patients 4049*
Normal mammogram does not rule out
possibility of cancer completely
Monthly breast self-exam (BSE)?
What Mammograms Show
Two of the most important mammographic
indicators of breast cancers
Masses; spiculated mass,
Pleomorphioc Microcalcifications: Tiny flecks of
calcium like grains of salt in the soft tissue of the
breast that can sometimes indicate an early cancer

What if I have an abnormal mammogram?

Biopsy may be recommended
Fine Needle biopsy - Ultrasound directed
Needle biopsy - mammogram directed
Surgical biopsy
The tissue diagnosis is the most important information in
planning treatment
Most mammogram abnormalities are not cancer; most are due to
benign changes

Refer to a surgeon
Lump new, discrete, new in preexisting
nodularity, asymmetric nodularity that persists
following menstruation, abscess, recurrent cyst
Pain unilateral persistent in post menopausal
Nipple discharge women<50,sufficient to stain
cloths, all women >50
Change in skin contour or nipple
retraction/eczema
Strong family history
In summary
Any breast mass needs to be investigated as if it
is breast cancer
Despite above most breast masses are benign
Mammography is still controversial

Lecture Questions
1) NoteRiskfactorsforbreastcancer.IfthereisaLumpyouneedtogetaTISSUE
biopsy.
2) WhatistheevidencethatSBE(selfbreastexamination)actuallyreducesthe
mortalityratefrombreastcancer?None
Butitincreasesmorbidity(generalsickness)
Fibroadenoma is MOBILE. IT IS RUBBERY. It is also well
circumscribed. They can grow very rapidly. They can reach large
sizes. For this you do surgical excision.
3) Whataretheriskfactorsforductalcarcinoma?Youwillseemultiplecysts.
ButatypicalductalhyperplasiaisaDEFINITErisk.
4) Riskfactorfordaughterwhomomhadbreastcancer?Havingamenstrualcycleis
ariskfactor.ThereforeearlymenarcheisaRISK.BeingpregnancyEarlyis
protective.NotBreastfeedingwillbeariskfactor.However***Radiationofthe
chestforlymphomawhenshewas9yearsoldisthebiggestrisk***
5) Genesassociatedwithbreastcancer:HER2(biomarker),BRCA1,p53,PTEN
6) Nippleseemstobedifferentheightthanotherheight.WhatOTHERfindingscan
indicatebreastcancer?ItcanmetastasizetoBoneandcausebonepain.Canalso
causebloodydischarge,pebbledswellingofskin,indrawnnipple.
7) Hardnontenderfixedlump.Nochildren.Motherdiedofbreastcancerat65.
SpiculatedmassandpleomorphiocMicrocalcificationsindicatescancer.
8) underlyinginfiltratingductalcarcinomaisindicativeofPagets
9) Whatistheworstprognosisofbreastcancer?Bonepain**Thisindicatesbony
metastasis.Nocurebuttheycangivebisphosphonates.3oroverlymphnode
involvementhasapoorprognosis.
Thepreferredmanagementofan80yearoldwhohasbreastcancerandhas
infiltratingductcellcarninomaisaLumpectomywithaxillarynodedissection,
postoperativeradiationandhormonaltherapy.***youhavetogivepatients
severaloptionstoo***!!!