Randomized trials of radiation after breast-conserving surgery (BCS) for ductal carcinoma in situ... more Randomized trials of radiation after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) found substantial rates of recurrence, with half of the recurrences being invasive. Decreasing local recurrence rates for invasive breast carcinoma have been observed and are largely attributed to improvements in systemic therapy. In this study, we examine recurrence rates after BCS for DCIS over 3 decades at one institution. We retrospectively reviewed a prospectively maintained database of DCIS patients undergoing BCS from 1978 to 2010. Cox proportional hazard models were used to investigate the association between the treatment period and recurrence, controlling for other variables. Overall, 363 (12 %) recurrences among 2996 cases were observed. Median follow-up for patients without recurrence was 75 months (range 0-30 years); 732 patients were followed for ≥10 years. The 5-year recurrence rate for the period 1978-1998 was 13.6 versus 6.6 % for the period 1999-2010 [hazard ratio (HR) 0.62, p < 0.0001]. Controlling for age, family history, presentation, nuclear grade, necrosis, number of excisions, margin status, radiation, and endocrine therapy, treatment period remained significantly associated with recurrence, with later years associated with a lower HR (0.74, p = 0.02) compared to earlier. After stratification by radiation use, association of recurrence with treatment period persisted in those treated without radiation (HR 0.62, p = 0.003). Recurrence rates for DCIS have fallen over time, with increases in screen detection, negative margins, and use of adjuvant therapies only partially explaining this decrease. The unexplained decline persists in women not receiving radiation, suggesting it is not due to changes in radiation efficacy but may be due to improvements in radiologic detection and pathologic assessment.
Historically, multiple ipsilateral breast cancer (MIBC) has been a contraindication to breast-con... more Historically, multiple ipsilateral breast cancer (MIBC) has been a contraindication to breast-conserving therapy (BCT). We report the feasibility of BCT in MIBC from the ACOSOG Z11102 trial [Alliance], a single arm noninferiority trial of BCT for women with two or three sites of malignancy in the ipsilateral breast. Women who enrolled preoperatively in ACOSOG Z11102 were evaluated for conversion to mastectomy and need for reoperation to obtain negative margins. Characteristics of women who successfully underwent BCT and those who converted to mastectomy were compared. Factors were examined for association with the need for margin reexcision. Of 198 patients enrolled preoperatively, 190 (96%) had 2 foci of disease. Median size of the largest tumor focus was 1.5 (range 0.1-7.0) cm; 49 patients (24.8%) had positive nodes. There were 14 women who underwent mastectomy due to positive margins, resulting in a conversion to mastectomy rate of 7.1% (95% confidence interval [CI] 3.9-10.6%). O...
Approximately 20% of breast cancer survivors develop breast cancer-related lymphedema (BCRL), and... more Approximately 20% of breast cancer survivors develop breast cancer-related lymphedema (BCRL), and current therapies are limited. We compared acupuncture (AC) to usual care wait-list control (WL) for treatment of persistent BCRL. Women with moderate BCRL lasting greater than six months were randomized to AC or WL. AC included twice weekly manual acupuncture over six weeks. We evaluated the difference in circumference and bioimpedance between affected and unaffected arms. Responders were defined as having a decrease in arm circumference difference greater than 30% from baseline. We used analysis of covariance for circumference and bioimpedance measurements and Fisher's exact to determine the proportion of responders. Among 82 patients, 73 (89%) were evaluable for the primary endpoint (36 in AC, 37 in WL). 79 (96%) patients received lymphedema treatment before enrolling in our study; 67 (82%) underwent ongoing treatment during the trial. We found no significant difference between g...
Breast cancer research and treatment, Jan 24, 2018
Although quality of life (QoL) improves over time for most breast cancer survivors (BCS), BCS may... more Although quality of life (QoL) improves over time for most breast cancer survivors (BCS), BCS may show different patterns of QoL. This study sought to identify distinct QoL trajectories among BCS and to examine characteristics associated with trajectory group membership. BCS (N = 653) completed baseline assessments within 8 months of diagnosis. QoL was assessed by the Functional Assessment of Cancer Therapy-Breast (FACT-B) at baseline and 6, 12, and 18 months later. Finite mixture modeling was used to determine QoL trajectories of the trial outcome index (TOI; a composite of physical well-being, functional well-being, and breast cancer-specific subscales) and emotional and social/family well-being subscales. Chi-square tests and F tests were used to examine group differences in demographic, cancer-related, and psychosocial variables. Unique trajectories were identified for all three subscales. Within each subscale, the majority of BCS had consistently medium or high QoL. The TOI ana...
Fibroepithelial lesions (FELs) are the most frequent breast tumors in adolescent females. The pub... more Fibroepithelial lesions (FELs) are the most frequent breast tumors in adolescent females. The pubertal hormonal surge could impact the growth and microscopic appearance of FELs in this age group. In this study, we evaluate the morphology and clinical behavior of FELs in adolescents. We searched the 1992-2012 pathology data base for FELs in females 18 years old or younger (F ≤18 years). Seven FELs from 1975 to 1983 were also included. Three pathologists reviewed all available material. Patient (pt) characteristics and follow-up information were obtained from electronic medical records. Forty-eight F ≤18 years had 54 FELs with available slides. Thirty (67%) pts were Caucasian, 12 (27%) African-American, two (4%) Hispanic, one (2%) Asian; three were of unknown race/ethnicity. Median age at diagnosis was 16 years. Median age at menarche was 12 years; most (96%) FELs occurred after menarche (median interval 48 months). All patients underwent lumpectomy; one required subsequent mastectomy. The FELs were 34 fibroadenomas (FAs) (11 usual, 23 juvenile), and 20 phyllodes tumors (PTs) (16 benign, one borderline and three malignant). Eight (35%) juvenile FAs showed slight intratumoral heterogeneity. The mean mitotic rate was 1.3 mitoses/10 high-power fields (HPFs) (range, 0-6) in usual FAs, 1.8/10 HPFs in juvenile FAs, 3.1/10 HPFs in benign PTs, 10/10 HPFs in the borderline PT and 17/10 HPFs in malignant PTs. The mean follow-up for 29 pts with 33 FELs was 44 months. Two (10%) PTs recurred locally (a benign PT at 18 months, and a borderline PT at 11 months). Both recurrent PTs had microscopic margins <1 mm. Mitotic activity in FAs from adolescents can be substantial and this finding should be interpreted cautiously. Awareness of the morphologic features of FELs in adolescents is important to avoid overdiagnosis of PTs, which can lead to additional unnecessary and potentially disfiguring surgery.
57 Background: Perioperative MRI is frequently obtained in women with breast cancer; however, stu... more 57 Background: Perioperative MRI is frequently obtained in women with breast cancer; however, studies have not shown decreased rates of re-excision, and some report unnecessary increases in mastectomy rates. We examined LRR rates among women with DCIS who underwent perioperative MRI as compared to those who did not. Methods: All women who underwent breast-conserving surgery for DCIS in 1997-2010 were included from a prospectively maintained database. Patient characteristics and rates of LRR were compared in women with and without an MRI. Univariate and multivariate analyses were performed. Analysis was repeated in the subset of women who did not receive RT. Results: 2,321 cases were identified; 596 had MRI and 1,725 did not. Women who had MRI were younger, more likely to be premenopausal, have a family history of breast cancer, have a clinical presentation, receive RT and endocrine therapy, be treated in later years, and had fewer close/positive margins. At median follow-up of 57 mo...
In the setting where determining extent of residual disease is key for surgical planning after ne... more In the setting where determining extent of residual disease is key for surgical planning after neoadjuvant chemotherapy (NAC), herein we evaluate reliability of MRI in predicting pathologic complete response (pCR) of the breast primary and axillary nodes following NAC. Patients who had MRI before and after NAC between 06/2014-08/2015 were identified in a prospective database following IRB approval. Post NAC-MRI of the breast and axillary nodes was correlated with residual disease on final pathology. PCR was defined as absence of invasive and in situ disease. We analyzed 129 breast cancers. Median patient age was 50.8 years (range 27.2-80.6). Tumors were HER2 amplified in 52/129 (40%), estrogen receptor-positive/HER2-negative in 46/129 (36%) and triple negative in 31/129 (24%), with respective pCR rates of 50%, 11% and 29%. Median tumor size pre- and post-NAC MRI were 4.1cm and 1.45cm, respectively. MRI had a positive predictive value of 63.4% (26/41) and negative predictive value of 84.1% (74/88) for in-breast pCR. Axillary nodes were abnormal on pre-NAC MRI in 97 cases; 65 had biopsy-confirmed metastases. The nodes normalized on post-NAC MRI in 33/65 (51%); axillary pCR was present in 22/33 (67%). In 32 patients with proven nodal metastases and abnormal nodes on post-NAC MRI, 11 achieved axillary pCR. In 32 patients with normal nodes on pre- and post-NAC MRI, 6 (19%) had metastasis on final pathology. Radiologic complete response by MRI does not predict pCR with adequate accuracy to replace pathologic evaluation of the breast tumor and axillary nodes.
Women with ductal carcinoma in situ (DCIS) are increasingly choosing bilateral mastectomy. We sou... more Women with ductal carcinoma in situ (DCIS) are increasingly choosing bilateral mastectomy. We sought to quantify rates of contralateral breast cancer (CBC) and ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) for DCIS, and to compare risk factors for CBC and IBTR. From 1978 to 2011, DCIS patients undergoing BCS with a contralateral breast at risk were identified from a prospectively maintained database. The association of clinicopathologic and treatment factors with CBC and IBTR were evaluated using Kaplan-Meier analysis, multivariable Cox regression, and competing risk regression (CRR). Of 2759 patients identified, 151 developed CBC and 344 developed IBTR. Five- and 10-year Kaplan-Meier CBC rates were 3.2 and 6.4%. Overall, 10-year IBTR rates were 2.5-fold higher than CBC rates, and, without radiation, 4-fold higher. On CRR, 5- and 10-year rates were 2.9 and 5.8% for CBC, and 7.8 and 14.5% for IBTR. CBC risk and invasive CBC risk were not significant...
Over the past several years, there has been an increasing rate of bilateral prophylactic mastecto... more Over the past several years, there has been an increasing rate of bilateral prophylactic mastectomy (BPM) and contralateral prophylactic mastectomy (CPM) surgeries. Since publication of the 2007 SSO position statement on the use of risk-reducing mastectomy, there have been significant advances in the understanding of breast cancer biology and treatment. The purpose of this manuscript is to review the current literature as a resource to facilitate a shared and informed decision-making process regarding the use of risk-reducing mastectomy.
International journal of surgical pathology, Jan 31, 2016
Background The clinical implications of the diagnosis of atypical ductal hyperplasia (ADH) and du... more Background The clinical implications of the diagnosis of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are very different. Yet there are "borderline" breast lesions that have characteristics of both ADH and DCIS. We examined interobserver diagnostic variability for such lesions and correlated pathologic features of the lesions with clinical outcomes. Methods We identified all cases of borderline ADH/DCIS lesions treated at our center from 1997 to 2010. Five specialized breast pathologists blinded to clinical outcomes independently reviewed all available slides from each case and were instructed to classify each as benign, ADH, or DCIS. A majority diagnosis (MajDx) was defined as a diagnosis agreed upon by ≥3 pathologists. Results A total of 105 women with borderline ADH/DCIS and slides available for review were identified. The MajDx was ADH in 84 (80%), and DCIS in 18 (17%). There were split diagnoses in 3 (3%). MajDx of DCIS correlated significantl...
Randomized trials of radiation after breast-conserving surgery (BCS) for ductal carcinoma in situ... more Randomized trials of radiation after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) found substantial rates of recurrence, with half of the recurrences being invasive. Decreasing local recurrence rates for invasive breast carcinoma have been observed and are largely attributed to improvements in systemic therapy. In this study, we examine recurrence rates after BCS for DCIS over 3 decades at one institution. We retrospectively reviewed a prospectively maintained database of DCIS patients undergoing BCS from 1978 to 2010. Cox proportional hazard models were used to investigate the association between the treatment period and recurrence, controlling for other variables. Overall, 363 (12 %) recurrences among 2996 cases were observed. Median follow-up for patients without recurrence was 75 months (range 0-30 years); 732 patients were followed for ≥10 years. The 5-year recurrence rate for the period 1978-1998 was 13.6 versus 6.6 % for the period 1999-2010 [hazard ratio (HR) 0.62, p < 0.0001]. Controlling for age, family history, presentation, nuclear grade, necrosis, number of excisions, margin status, radiation, and endocrine therapy, treatment period remained significantly associated with recurrence, with later years associated with a lower HR (0.74, p = 0.02) compared to earlier. After stratification by radiation use, association of recurrence with treatment period persisted in those treated without radiation (HR 0.62, p = 0.003). Recurrence rates for DCIS have fallen over time, with increases in screen detection, negative margins, and use of adjuvant therapies only partially explaining this decrease. The unexplained decline persists in women not receiving radiation, suggesting it is not due to changes in radiation efficacy but may be due to improvements in radiologic detection and pathologic assessment.
Historically, multiple ipsilateral breast cancer (MIBC) has been a contraindication to breast-con... more Historically, multiple ipsilateral breast cancer (MIBC) has been a contraindication to breast-conserving therapy (BCT). We report the feasibility of BCT in MIBC from the ACOSOG Z11102 trial [Alliance], a single arm noninferiority trial of BCT for women with two or three sites of malignancy in the ipsilateral breast. Women who enrolled preoperatively in ACOSOG Z11102 were evaluated for conversion to mastectomy and need for reoperation to obtain negative margins. Characteristics of women who successfully underwent BCT and those who converted to mastectomy were compared. Factors were examined for association with the need for margin reexcision. Of 198 patients enrolled preoperatively, 190 (96%) had 2 foci of disease. Median size of the largest tumor focus was 1.5 (range 0.1-7.0) cm; 49 patients (24.8%) had positive nodes. There were 14 women who underwent mastectomy due to positive margins, resulting in a conversion to mastectomy rate of 7.1% (95% confidence interval [CI] 3.9-10.6%). O...
Approximately 20% of breast cancer survivors develop breast cancer-related lymphedema (BCRL), and... more Approximately 20% of breast cancer survivors develop breast cancer-related lymphedema (BCRL), and current therapies are limited. We compared acupuncture (AC) to usual care wait-list control (WL) for treatment of persistent BCRL. Women with moderate BCRL lasting greater than six months were randomized to AC or WL. AC included twice weekly manual acupuncture over six weeks. We evaluated the difference in circumference and bioimpedance between affected and unaffected arms. Responders were defined as having a decrease in arm circumference difference greater than 30% from baseline. We used analysis of covariance for circumference and bioimpedance measurements and Fisher's exact to determine the proportion of responders. Among 82 patients, 73 (89%) were evaluable for the primary endpoint (36 in AC, 37 in WL). 79 (96%) patients received lymphedema treatment before enrolling in our study; 67 (82%) underwent ongoing treatment during the trial. We found no significant difference between g...
Breast cancer research and treatment, Jan 24, 2018
Although quality of life (QoL) improves over time for most breast cancer survivors (BCS), BCS may... more Although quality of life (QoL) improves over time for most breast cancer survivors (BCS), BCS may show different patterns of QoL. This study sought to identify distinct QoL trajectories among BCS and to examine characteristics associated with trajectory group membership. BCS (N = 653) completed baseline assessments within 8 months of diagnosis. QoL was assessed by the Functional Assessment of Cancer Therapy-Breast (FACT-B) at baseline and 6, 12, and 18 months later. Finite mixture modeling was used to determine QoL trajectories of the trial outcome index (TOI; a composite of physical well-being, functional well-being, and breast cancer-specific subscales) and emotional and social/family well-being subscales. Chi-square tests and F tests were used to examine group differences in demographic, cancer-related, and psychosocial variables. Unique trajectories were identified for all three subscales. Within each subscale, the majority of BCS had consistently medium or high QoL. The TOI ana...
Fibroepithelial lesions (FELs) are the most frequent breast tumors in adolescent females. The pub... more Fibroepithelial lesions (FELs) are the most frequent breast tumors in adolescent females. The pubertal hormonal surge could impact the growth and microscopic appearance of FELs in this age group. In this study, we evaluate the morphology and clinical behavior of FELs in adolescents. We searched the 1992-2012 pathology data base for FELs in females 18 years old or younger (F ≤18 years). Seven FELs from 1975 to 1983 were also included. Three pathologists reviewed all available material. Patient (pt) characteristics and follow-up information were obtained from electronic medical records. Forty-eight F ≤18 years had 54 FELs with available slides. Thirty (67%) pts were Caucasian, 12 (27%) African-American, two (4%) Hispanic, one (2%) Asian; three were of unknown race/ethnicity. Median age at diagnosis was 16 years. Median age at menarche was 12 years; most (96%) FELs occurred after menarche (median interval 48 months). All patients underwent lumpectomy; one required subsequent mastectomy. The FELs were 34 fibroadenomas (FAs) (11 usual, 23 juvenile), and 20 phyllodes tumors (PTs) (16 benign, one borderline and three malignant). Eight (35%) juvenile FAs showed slight intratumoral heterogeneity. The mean mitotic rate was 1.3 mitoses/10 high-power fields (HPFs) (range, 0-6) in usual FAs, 1.8/10 HPFs in juvenile FAs, 3.1/10 HPFs in benign PTs, 10/10 HPFs in the borderline PT and 17/10 HPFs in malignant PTs. The mean follow-up for 29 pts with 33 FELs was 44 months. Two (10%) PTs recurred locally (a benign PT at 18 months, and a borderline PT at 11 months). Both recurrent PTs had microscopic margins <1 mm. Mitotic activity in FAs from adolescents can be substantial and this finding should be interpreted cautiously. Awareness of the morphologic features of FELs in adolescents is important to avoid overdiagnosis of PTs, which can lead to additional unnecessary and potentially disfiguring surgery.
57 Background: Perioperative MRI is frequently obtained in women with breast cancer; however, stu... more 57 Background: Perioperative MRI is frequently obtained in women with breast cancer; however, studies have not shown decreased rates of re-excision, and some report unnecessary increases in mastectomy rates. We examined LRR rates among women with DCIS who underwent perioperative MRI as compared to those who did not. Methods: All women who underwent breast-conserving surgery for DCIS in 1997-2010 were included from a prospectively maintained database. Patient characteristics and rates of LRR were compared in women with and without an MRI. Univariate and multivariate analyses were performed. Analysis was repeated in the subset of women who did not receive RT. Results: 2,321 cases were identified; 596 had MRI and 1,725 did not. Women who had MRI were younger, more likely to be premenopausal, have a family history of breast cancer, have a clinical presentation, receive RT and endocrine therapy, be treated in later years, and had fewer close/positive margins. At median follow-up of 57 mo...
In the setting where determining extent of residual disease is key for surgical planning after ne... more In the setting where determining extent of residual disease is key for surgical planning after neoadjuvant chemotherapy (NAC), herein we evaluate reliability of MRI in predicting pathologic complete response (pCR) of the breast primary and axillary nodes following NAC. Patients who had MRI before and after NAC between 06/2014-08/2015 were identified in a prospective database following IRB approval. Post NAC-MRI of the breast and axillary nodes was correlated with residual disease on final pathology. PCR was defined as absence of invasive and in situ disease. We analyzed 129 breast cancers. Median patient age was 50.8 years (range 27.2-80.6). Tumors were HER2 amplified in 52/129 (40%), estrogen receptor-positive/HER2-negative in 46/129 (36%) and triple negative in 31/129 (24%), with respective pCR rates of 50%, 11% and 29%. Median tumor size pre- and post-NAC MRI were 4.1cm and 1.45cm, respectively. MRI had a positive predictive value of 63.4% (26/41) and negative predictive value of 84.1% (74/88) for in-breast pCR. Axillary nodes were abnormal on pre-NAC MRI in 97 cases; 65 had biopsy-confirmed metastases. The nodes normalized on post-NAC MRI in 33/65 (51%); axillary pCR was present in 22/33 (67%). In 32 patients with proven nodal metastases and abnormal nodes on post-NAC MRI, 11 achieved axillary pCR. In 32 patients with normal nodes on pre- and post-NAC MRI, 6 (19%) had metastasis on final pathology. Radiologic complete response by MRI does not predict pCR with adequate accuracy to replace pathologic evaluation of the breast tumor and axillary nodes.
Women with ductal carcinoma in situ (DCIS) are increasingly choosing bilateral mastectomy. We sou... more Women with ductal carcinoma in situ (DCIS) are increasingly choosing bilateral mastectomy. We sought to quantify rates of contralateral breast cancer (CBC) and ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) for DCIS, and to compare risk factors for CBC and IBTR. From 1978 to 2011, DCIS patients undergoing BCS with a contralateral breast at risk were identified from a prospectively maintained database. The association of clinicopathologic and treatment factors with CBC and IBTR were evaluated using Kaplan-Meier analysis, multivariable Cox regression, and competing risk regression (CRR). Of 2759 patients identified, 151 developed CBC and 344 developed IBTR. Five- and 10-year Kaplan-Meier CBC rates were 3.2 and 6.4%. Overall, 10-year IBTR rates were 2.5-fold higher than CBC rates, and, without radiation, 4-fold higher. On CRR, 5- and 10-year rates were 2.9 and 5.8% for CBC, and 7.8 and 14.5% for IBTR. CBC risk and invasive CBC risk were not significant...
Over the past several years, there has been an increasing rate of bilateral prophylactic mastecto... more Over the past several years, there has been an increasing rate of bilateral prophylactic mastectomy (BPM) and contralateral prophylactic mastectomy (CPM) surgeries. Since publication of the 2007 SSO position statement on the use of risk-reducing mastectomy, there have been significant advances in the understanding of breast cancer biology and treatment. The purpose of this manuscript is to review the current literature as a resource to facilitate a shared and informed decision-making process regarding the use of risk-reducing mastectomy.
International journal of surgical pathology, Jan 31, 2016
Background The clinical implications of the diagnosis of atypical ductal hyperplasia (ADH) and du... more Background The clinical implications of the diagnosis of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are very different. Yet there are "borderline" breast lesions that have characteristics of both ADH and DCIS. We examined interobserver diagnostic variability for such lesions and correlated pathologic features of the lesions with clinical outcomes. Methods We identified all cases of borderline ADH/DCIS lesions treated at our center from 1997 to 2010. Five specialized breast pathologists blinded to clinical outcomes independently reviewed all available slides from each case and were instructed to classify each as benign, ADH, or DCIS. A majority diagnosis (MajDx) was defined as a diagnosis agreed upon by ≥3 pathologists. Results A total of 105 women with borderline ADH/DCIS and slides available for review were identified. The MajDx was ADH in 84 (80%), and DCIS in 18 (17%). There were split diagnoses in 3 (3%). MajDx of DCIS correlated significantl...
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