Benefits Of Contralateral Prophylactic Mastectomy Research Articles

Abstract PO1-08-10: Impact of Oncologist-Led Genetic Counseling and Testing on Prophylactic Mastectomy Rates Among Multi-Ethnic Women with Operable Breast Cancer

Abstract Introduction: Approximately 5-10% of breast cancers are attributed to an inherited pathogenic variant (PV) in breast cancer predisposition genes, such as BRCA1 and BRCA2. Identifying women with hereditary breast cancer syndromes is critical to inform risk-appropriate screening and prevention strategies. For example, contralateral prophylactic mastectomy (CPM) has been shown to reduce the risk of new breast primaries without a demonstrated survival benefit. In a prior study, we found that women with pathogenic/likely pathogenic (P/LP) variants were over four times more likely to undergo CPM compared to those with benign/likely benign (B/LB) variants. In recent years due to expanded indications for genetic testing and social distancing during the COVID-19 pandemic, oncologist-led genetic testing and telehealth genetic counseling has gradually replaced in-person genetic counseling visits. We aimed to understand how changes in the delivery of genetic counseling and testing services impacted CPM rates among multi-ethnic women with operable breast cancer in the post COVID-19 period. Methods: We conducted a retrospective cohort study among 1,080 women diagnosed with unilateral breast cancer who underwent germline genetic testing between 2013 and 2022 at Columbia University Irving Medical Center (CUIMC) in New York, NY. The pre COVID-19 period was defined as 2013-2019 and the post COVID-19 period as 2020-2022. Demographics, including age, race/ethnicity and marital status, and clinical characteristics, such as year of diagnosis, breast cancer stage, tumor hormone receptor status, family history of breast cancer, and genetic test results, were extracted from the electronic health record (EHR). We used univariable and multivariable logistic regression analyses to estimate the odds ratio (OR) and 95% confidence interval (95% CI) associated with each variable and receipt of CPM. Results: Among 1080 evaluable women, mean age at diagnosis was 51.2 years old (SD, 12.3) with 39.6% non-Hispanic White, 27.8% Hispanic, 11.4% non-Hispanic Black, 9.0% Asian, and 12.2% multi-racial/other. Within the overall study population, 12.1% of women had P/LP variants and 21.4% had variants of unknown significance (VUS) results. Non-Hispanic Whites and Blacks had the highest frequency of P/LP variants, whereas VUS results were more common among Hispanics and Asians (see Table). Twenty-three percent of women in the study population underwent CPM. In multivariable analysis, younger age at diagnosis, more advanced stage breast cancer, family history of breast cancer, Hispanic race and P/LP results on germline genetic testing were associated with increased CPM rates. Hispanic women were over 60% more likely to undergo CPM compared to non-Hispanic White women (adjusted OR=1.63, 95% CI=1.07-2.47). No significant change in CPM rates was observed in the post-COVID era compared to the pre-COVID era. Conclusion: We aimed to understand how the transition to telehealth and oncologist-led genetic testing affected CPM rates. Although we did not observe a change in CPM rates in the post-COVID era, Hispanic women had significantly more VUS results and were over 60% more likely to undergo CPM compared to non-Hispanic White women. In future studies, we hope to improve risk communication of genetic test results and the risks and benefits of CPM, particularly in vulnerable and underserved populations. Table 1 Genetic testing results and rates of contralateral prophylactic mastectomy stratified by race/ethnicity in women diagnosed with operable breast cancer and undergoing germline genetic testing from 2013-2022 at Columbia University Irving Medical Center, New York, NY Citation Format: Alissa Michel, Kelly Luo, Vicky Ro, Matthew Fine, Meghna Trivedi, Wendy Chung, Roshni Rao, Tarsha Jones, Elana Levinson, Carrie Koval-Burt, Donna Russo, Ilana Chilton, Rita Kukafka, Katherine Crew. Impact of Oncologist-Led Genetic Counseling and Testing on Prophylactic Mastectomy Rates Among Multi-Ethnic Women with Operable Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-08-10.

Trend and survival benefit of contralateral prophylactic mastectomy among men with stage I–III unilateral breast cancer in the USA, 1998–2016

Our study aimed to explore temporal trends and survival benefit of contralateral prophylactic mastectomy (CPM) in male breast cancer (MBC). Men with stage I-III unilateral breast cancer between 1998 and 2016 were identified from the surveillance, epidemiology, and end results (SEER). We compared CPM rate over the study period using the Cochrane-Armitage test for trend. Logistic regression model was used to test for factors predicting CPM. Survival analysis was conducted in patients who underwent CPM or unilateral mastectomy (UM) with a first diagnosis of unilateral breast cancer. Kaplan-Meier curve and univariate and multivariable Cox proportional hazards regression analyses were performed to compare overall survival (OS) and breast cancer-specific survival (BCSS) between CPM and UM groups. Propensity score matching was adopted to balance baseline characteristics. 5118 MBC cases were included in the present study, with 4.1% (n = 209) patients underwent CPM. The proportion of men undergoing CPM increased from 1.7 in 1998 to 6.3% in 2016 (P < 0.0001). Young age, recent years of diagnosis, higher tumor grade and lower T stage were significantly associated with CPM. A cohort of 3566 patients were enrolled in survival analysis with a median follow-up of 65months. CPM was associated with better OS (HR 0.58, 95% CI 0.37-0.89, P = 0.022) rather than BCSS (HR 0.57, 95% CI 0.29-1.11, P = 0.153) compared with UM. In propensity score-matched model, CPM was not an independent prognostic factor for OS (HR 0.83, 95% CI 0.46-1.52, P = 0.553) and BCSS (HR 0.98, 95% CI 0.39-2.47, P = 0.970). Our study revealed a dramatic increase in CPM utilization among MBC, especially in young patients. However, CPM provides no survival benefit for MBC compared with UM, indicating the decision of CPM should be fully discussed.

Abstract OT-20-01: Genetic testing for all breast cancer patients (get facts)

Abstract Background: There is evidence that increases in germline cancer genetic testing result in higher rates of contralateral prophylactic mastectomy (CPM) in newly diagnosed breast cancer (BC) patients, even among those with negative results. Unlike carriers of BRCA pathogenic variants (PV), the risks of contralateral breast cancer (CBC) and benefits of CPM for women with PV in moderate penetrance genes are not well studied. There is a critical need to determine how to best counsel BC patients about their personal CBC risk and surgical decisions. Trial design: Newly diagnosed BC patients are randomized 1:1 to quantitative or standard post-genetic test cancer risk counseling methods by genetic counselors. Quantitative counseling includes personalized CBC risk estimates. For patients with a PV in a BC risk gene, CBC risk estimates are calculated via the “ASK2ME” decision tool (https://ask2me.org/). For those without a BC-associated PV, CBC risk estimates are calculated via a validated model “CBCRisk” (https://cbc-predictor-utd.shinyapps.io/CBCRisk/).Standard counseling does not typically include specific CBC risk estimates.Eligibility criteria: All patients over 18 with newly diagnosed invasive or in situ unilateral BC considering genetic testing at Dana-Farber/Brigham and Women’s Cancer Center are eligible. Exclusion criteria include a diagnosis of previous BC, metastatic or bilateral BC, hematologic malignancy, prior or active other malignancy, prior multi-gene panel testing, known medical or surgical contraindication to surgery and/or CPM.Specific aims: The primary aims are to 1) compare changes in patients’ personal CBC risk assessment before/after quantitative versus standard counseling; 2) determine changes in patients’ propensity to choose CPM before/after quantitative versus standard counseling. The secondary aims are to: 1) compare CPM rates; 2) determine concordance between patient and surgeon assessment of CBC risk; 3) evaluate patient genetic testing satisfaction via the Genetic Testing Satisfaction Survey administered post-counseling; 4) measure patient anxiety via the PROMIS Anxiety Survey administered pre- and post-counseling, at 6 months and 2 years; and 5) measure patient decisional regret for both undergoing genetic testing and their surgery choices at 6 months and 2 years; all by quantitative versus standard counseling arms. Statistical methods: For aim 1, the difference between patients’ reported personal CBC risk and true risk before and after counseling will be determined. True risk will be based on the ASK2ME/CBCRisk estimates. We hypothesize that the difference between the true and estimated risk will be smaller post-counseling, and smaller in the quantitative counseling versus standard arm. Assuming an expected difference of 5% and expected standard deviation of 20%, 199 patients are needed for each arm to achieve 80% power and type I error of 5% (based on a two-sample t-test). For aim 2, to determine propensity to undergo CPM, patient responses will be assigned a numeric value: Very Unlikely (1), Somewhat unlikely (2), Unsure (3), Somewhat likely (4), Very likely (5). For each patient we will then calculate the difference in scores before/after counseling. Our hypothesis is that differences will be greater in the quantitative arm. Assuming an expected difference of 0.8 and expected standard deviation of 3, 175 patients are needed for each arm to achieve 80% power and type I error rate of 5% (based on a two-sample t-test). Accrual: Recruitment began on June 8, 2020; there are currently 9 of the target 450 patients enrolled. Funding Support: Sponsored Research Agreement with Myriad Laboratories, Inc. and a Brigham and Women’s Hospital Department of Surgery Robert T. Osteen Junior Fellowship Award. PI: Anna Weiss, aweiss5@bwh.harvard.edu, @DrAnnaWeiss Citation Format: Anna Weiss, Danielle Braun, Jill Stopfer, Daniel Desantis, Meaghan Dwan, Dillon Davis, Anjali Jha, Laura Dominici, Shoshana Rosenberg, Tari A. King, Elizabeth A Mittendorf, Mehra Golshan, Huma Q Rana, Judy E Garber. Genetic testing for all breast cancer patients (get facts) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-20-01.

Second primary breast cancer after unilateral mastectomy alone or with contralateral prophylactic mastectomy.

BackgroundAn increasing number of patients undergo contralateral prophylactic mastectomy (CPM) for unilateral breast cancer. However, the benefit of CPM has not been quantified in the setting of contemporary breast cancer therapy.MethodsWe performed an analysis of 180 068 patients in the Surveillance, Epidemiology, and End Results (SEER) database, diagnosed with unilateral ductal breast carcinoma between 1998 and 2013 and treated with unilateral mastectomy (UM) or CPM. UM was performed in 146 213 patients (81.2%); CPM was performed in 33 855 patients (19.8%). Primary outcome of interest was cumulative incidence of a second primary breast cancer in the ipsilateral or contralateral breast greater than 3 months after initial diagnosis. Cumulative incidence analysis was based on a Cox proportional model to generate curves of second primary breast cancer in any breast, ipsilateral breast only, or contralateral breast only.ResultsPatients who underwent CPM had a significantly reduced incidence of second primary breast cancer 10 and 15 years after surgery (CPM 0.93% [0.73%, 1.12%] vs UM 4.44% [4.28%, 4.60%]). Patients who underwent CPM had significantly lower adjusted hazard of second primary breast cancer when compared with UM (HR 0.38 vs 1.0, P < .0001).ConclusionsCPM offers some protection from a second primary breast cancer, attributable to a reduced incidence in the contralateral breast. These findings provide additional information to providers and patients as they make decisions regarding surgical management. They should also be interpreted in the context of the absolute incidence of second primary breast cancer after UM and previous literature demonstrating no survival benefit.

Risk-to-Benefit Relationship of Contralateral Prophylactic Mastectomy: The Argument for Bilateral Mastectomies with Immediate Reconstruction.

The increasing trend of women with unilateral breast cancer to electively undergo contralateral prophylactic mastectomy in addition to treatment of the index breast has been controversial. The authors set out to better frame the risks and benefits of contralateral prophylactic mastectomy in the treatment of unilateral breast cancer by evaluating outcomes of a large, consecutive cohort of patients. An institutional review board-approved review of a single-surgeon (N.T.) experience (2013 to 2018) was conducted of all consecutive patients with unilateral breast cancer treated with mastectomy and immediate reconstruction. Patient characteristics, surgical pathologic results, and 30-day complications were assessed. Outcomes of patients with unilateral cancer who underwent unilateral mastectomy versus bilateral mastectomy (with one breast being contralateral prophylactic mastectomy) were compared. Logistic regression models evaluated various risk factors for potential associations with positive pathologic findings in the contralateral prophylactic mastectomy specimen and/or postoperative complications. Of 244 patients, 68 (27.9 percent) underwent unilateral mastectomy and 176 (72.1 percent) underwent contralateral prophylactic mastectomy. Surgical pathologic results of the prophylactic breast revealed occult ductal carcinoma in situ or invasive cancer in 13 patients (7.3 percent) and lobular carcinoma in situ in eight patients (4.6 percent). Incidence of complications was similar between groups [unilateral mastectomy, 19.12 percent (n = 13); contralateral prophylactic mastectomy, 13.07 percent (n = 23); p = 0.234]. Immediate reconstruction for unilateral mastectomy and contralateral prophylactic mastectomy have similar complication risk profiles, among patients as a whole and between individual breasts. These findings contribute to our understanding of the clinical impact prophylactic mastectomy and reconstruction may have on optimizing the counseling among extirpative surgeons, reconstructive surgeons, and patients. Therapeutic, III.

Practitioner Opinion on Contralateral Prophylactic Mastectomy: How Do We Steer a Patient-Driven Discussion?

Contralateral prophylactic mastectomy (CPM) is increasing despite a recent statement from The American Society of Breast Surgeons discouraging average-risk women with unilateral breast cancer (BC) from undergoing CPM. The objective of our study was to conduct a needs assessment of BC health practitioners to gather information about their opinions, attitudes, and experiences surrounding CPM. The Ottawa Decision Support Framework was the theoretical framework for the development of the interview guide. Semistructured interviews were conducted until data saturation with a convenience sample of 16 BC practitioners (Ontario, Canada), including oncologic and reconstructive surgeons, medical oncologists, and nurse navigators. Nearly all practitioners identified the discussion regarding CPM as patient-initiated. The majority of practitioners (13/16) described their role as supporting the patient in the decision-making process. Practitioners described educating patients on the lack of survival benefit and in general discouraging CPM. Practitioners agreed that most patients demonstrate decisional conflict (11/16) as a barrier to decision-making, and it is a challenge to realign patients' understanding and expectations. Almost all practitioners (15/16) identified a need for information materials to help educate patients on the risks and benefits of CPM and to help realign expectations. Practitioners have identified CPM in average-risk women with unilateral BC as a patient-driven phenomenon that is on the rise, despite highlighting the increased risk of complications and lack of survival benefit. Our practitioner needs assessment identifies the need for a dynamic decision aid to help guide the shared decision-making process for practitioners and patients.

Abstract: Contralateral Prophylactic Mastectomy: The Argument for Bilateral Mastectomies and Reconstruction

BACKGROUND: The increasing trend of women with unilateral breast cancer to electively undergo contralateral prophylactic mastectomy (CPM) in addition to treatment of the index breast has been the source of much debate. This trend has been primarily patient-driven, with conflicting, objective evidence supporting CPM. Critics have cautioned against the rising rates of CPM, questioning its indications and the possibility of increased risk over unilateral treatment. As such, any information that can help practitioners better guide their patients towards the most beneficial and risk-reducing options is critical. The authors set out to better frame the risks and benefits of CPM in the treatment of unilateral breast cancer by evaluating outcomes of a large, consecutive cohort of patients. METHODS: An IRB-approved review of a single-surgeon (NT) experience (2013–2018) was conducted of all consecutive patients with unilateral breast cancer treated with mastectomy and immediate reconstruction. Demographic data, comorbidities, and surgical pathology results were assessed. Thirty-day complication rates were recorded, including medical complications requiring readmission to the hospital and surgical complications requiring a return to the operating room. Outcomes were compared between patients with unilateral cancer who underwent unilateral mastectomy (UM) versus bilateral mastectomy (one breast being CPM). Logistic regression models evaluated various risk factors for potential associations with positive pathology in the CPM specimen and/or postoperative complications. RESULTS: A total of 244 patients were identified, 146 (59.8%) of which had autologous reconstruction and 98 (40.2%) had implant-based reconstruction. Of the 244 patients, 68 (27.9%) underwent UM and 176 (72.1%) underwent CPM. Of those undergoing CPM, surgical pathology results of the prophylactic breast revealed occult ductal carcinoma in situ or invasive cancer in 13 patients (7.39%) and lobular carcinoma in situ in 8 patients (4.55%). Logistic regression analysis showed no significant association between positive breast pathology and any of the potential factors assessed, including tobacco use, history of radiotherapy, or breast cancer (BRCA) gene status. Incidence of medical complications (4.41% UM vs. 5.68% CPM; p<1.00) and surgical complications (16.18% UM vs. 8.52% CPM; p<0.104) were similar between UM and CPM patients. With UM and CPM patients analyzed in aggregate, multivariable logistic regression revealed increased BMI as a significant risk factor for medical complications (OR=1.15; 95% CI 1.05 to 1.26). Regression models also identified diabetes mellitus to be significantly associated with having a surgical complication (OR=4.05; 95% CI 1.38 to 11.91). CONCLUSION: These results underscore the premise that women with unilateral breast cancer who elect to undergo CPM may have an oncologic benefit by identifying an occult neoplasm in patients who lack typical risk factors associated with bilateral disease, such as positive BRCA status. Moreover, the findings presented here also suggest CPM does not pose an increased risk of complications compared to unilateral treatment.

Abstract P5-22-14: Assessment of risk factors in women undergoing contralateral prophylactic mastectomy after breast cancer diagnosis: Experience at an academic medical center

Abstract Recently, the rates of contralateral prophylactic mastectomy (CPM) have increased significantly with no clear evidence of improvement in overall survival or breast cancer (BC) specific survival. In 2016, American Society of Breast Surgeons (ASBS) provided a consensus statement regarding when CPM should be-, can be- or may be offered and when it should be discouraged. In light of new recommendations, our study aimed to review factors that influenced the choice of CPM at our institution. Methods: This retrospective study was approved by the IRB. Patients who underwent CPM between January 2011 and May 2014 were included. Medical records were reviewed for documentation of risk factors that led to CPM. Patients were stratified into four categories based on the consensus statement. CPM “should be considered” included carriers of BRCA1/2 mutation, patients with strong FH (2 or more first degree relatives with BC) but not tested for BRCA and patients with history of mantle radiation; CPM “can be considered” included patients with intermediate FH (one first degree or multiple second/third degree relatives with BC), carriers of non-BRCA gene mutation, patients with prior history of BC and patients with strong FH but tested negative for BRCA; CPM “may be considered" included patients with psychological factors, those who denied adjuvant therapy and patients with multicentric disease in the index side. CPM “should be discouraged” included patients with advanced disease at the time of diagnosis, patients with weak FH (one second or third degree relative with BC) and patients with no significant FH or unknown FH. Results: Between January 2011 and May 2014, CPM was performed in 261 women ranging from 24 to 83 years (mean, 50 years). The number and percentage of women in each risk group is summarized in Table. Discussion: Based on the results, only 13% of the 261 women satisfied the criteria for when CPM "should be considered”, 38% for when CPM "can be or may be considered”, and in the remaining 49% CPM should have been discouraged. In light of the growing controversy regarding the overall benefit of CPM, it is important that the women with average-risk are well informed about the surgical risks vs. the benefits of CPM. Summary of the risks factors associated with contralateral prophylactic mastectomy (n=261)CPM should be considered for those at significant risk of CBC (total 13%) Carriers for BRCA 1/2 mutation2911.1%Strong Family history (patient not tested for BRCA)20.8%History of mantle radiation31.1%CPM can be considered for those at lower risk of CBC (total 30.6%) Intermediate family history6023%Carriers for non-BRCA gene mutation31.1%History of prior breast carcinoma135%Strong Family history, BRCA negative41.5%CPM may be considered for other reasons (total 7.6%) Psychological factors62.3%Patient denied adjuvant chemo or radiation therapy31.1%Multicentric disease in the index breast114.2%CPM should be discouraged (48.8%) Advanced disease at diagnosis41.5%Weak family history7829.8%No family history4115.6%Unknown family history, no other significant personal history51.9%CPM: contralateral prophylactic mastectomy; CBC: contralateral breast cancer Citation Format: Drobysheva A, Butt Y, Sahoo S. Assessment of risk factors in women undergoing contralateral prophylactic mastectomy after breast cancer diagnosis: Experience at an academic medical center [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-22-14.

Abstract P2-07-09: CPM rate among individuals with breast cancer who underwent multiplex gene testing for hereditary cancer: Single institution experience

Abstract Background: Availability of multiplex gene (MPG) testing for hereditary cancer has led to increase use of panel testing versus single gene testing for hereditary cancer. These panels include high, but also moderate penetrance genes. For some of these genes, associated cancer risk and risk management guidelines do not exist. Furthermore there is a high rate of variant of unknown significant (VUS) findings in non-BRCA genes. Currently, in the absence or minimal available data, health care providers and patients are faced with important risk management decisions, especially regarding preventive surgeries, such as prophylactic mastectomy. Currently, there is no data regarding prophylactic mastectomy rate among patients with breast cancer who underwent (MPG) testing. Therefore, our aim was to evaluate the rate of contralateral prophylactic mastectomy (CPM) in a cohort of individuals who underwent multiplex gene testing. Methods: Eight hundred thirty five patients with breast cancer who underwent MPG testing between the years 2013 and 2016 were identified using Institutional Clinical Cancer Genetics Database. Patients with pathogenic, likely pathogenic variants or who had a VUS were included in the analysis. Results: Of 835 patients with a diagnosis of breast cancer; 105 (13%) had a pathogenic or likely pathogenic mutation: 29 (28%) BRCA1, 26 (25%) BRCA2, 11 (11%) ATM, 2 (2%) BARD1, 3 (3%) BRIP, 9 (9%) CHEK2, 1 (1%) MSH2, 1 (1%) NBN, 5 (5%) PALB2, 4 (4%) PTEN, 1 (1%) RAD51C, 5 (5%) TP53, 4 (4%) CDH1, 2 (2%) MUTYH, 1 (1%) PMS2, 1 (1%) APC (1). A total of 102 (12%) VUS were found. Average age of diagnosis was 44 (Range 21-81). CPM rate was 32% (n=66) for the total cohort. Twenty nine % (n=19) of patients with non-BRCA mutations, 24.2% (n=16) with VUS and 46% (n=31) with BRCA mutations opted for CPM. Conclusion: Overall 32% of breast cancer patients with germline mutations or VUS opt for CPM at our institution. The rate for CPM in non- BRCA mutations carriers is high despite no available data regarding contralateral breast cancer risk and benefit of CPM. This finding should be validated in larger cohorts, including identification of reasons behind decision for CPM in these cohorts. Citation Format: Elsayegh N, Gutierrez Barrera AM, Kuerer HM, Hernandez ND, Litton JK, Arun BK. CPM rate among individuals with breast cancer who underwent multiplex gene testing for hereditary cancer: Single institution experience [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-09.

Commentary on the Consensus Statement of the American Society of Breast Surgeons on Contralateral Prophylactic Mastectomy

The increasing rate of contralateral prophylactic mastectomy (CPM) led the American Society of Breast Surgeons (ASBrS) to issue an evidence-based consensus statement on CPM, as well as a discussion guide that health care providers can use to facilitate shared decision making with patients considering CPM for unilateral breast cancer. This article suggests several ways to improve the discussion guide by eliciting patient values and preferences and by providing more current, detailed, and balanced information about the potential risks and benefits of CPM.

Contralateral Prophylactic Mastectomy Consensus Statement from the American Society of Breast Surgeons: Additional Considerations and a Framework for Shared Decision Making.

The American Society of Breast Surgeons (ASBrS) encourages an evidence-based and patient value focused approach to contralateral prophylactic mastectomy (CPM). The ASBrS convened a panel of experts to develop a consensus statement on CPM.1 The majority of women will obtain no oncologic benefit from CPM, and therefore CPM should be discouraged in average-risk women with unilateral breast cancer. Consideration of the patient’s preferences and values and an informed discussion of the risks and benefits of CPM is recommended for all patients pursuing mastectomy, along with a direct recommendation by the surgeon for or against CPM.

Abstract 2574: Outcomes of contralateral prophylactic mastectomy in relation to familial history: a decision analysis

Abstract Purpose Family history of breast cancer is associated with an increased risk of contralateral breast cancer (CBC) even in the absence of mutations in the breast cancer susceptibility genes BRCA1/2. We compared quality-adjusted survival outcomes after contralateral prophylactic mastectomy (CPM) with surveillance only (no CPM) among women with breast cancer in relation to degree of family history. Methods We created a microsimulation model for women with a first-degree, second-degree and no family history treated for a stage I, II, or III estrogen receptor (ER)-positive or -negative breast cancer at the ages of 40, 50, 60, and 70 years. The model incorporated a 10-year post-treatment period for risk of developing CBC and/or dying of the primary cancer or CBC. For each patient profile, we used 100,000 microsimulation trials to estimate the quality-adjusted life expectancy for two clinical strategies: CPM and no CPM. Results CPM had a minimal improvement on quality-adjusted life expectancy among women age 50 to 60 with no or a unilateral first or second-degree family history (range -.06 to 0.31) and was unfavorable for the majority of women age 70 with stage III breast cancer regardless of degree of family history (range -.08 to -.02). Sensitivity analysis showed the highest predicted benefit of CPM with 95% risk reduction was 0.57 QALY for a 40-year-old woman with stage I breast cancer who had a first-degree relative with bilateral breast cancer. Conclusion Women age 40 years with stage I breast cancer and a first-degree relative with bilateral breast cancer have a QALY benefit from CPM similar to that reported for BRCA1/2 mutation carriers. For the majority of women, having a family history does not improve the minimal effect of CPM on quality-adjusted life expectancy. Citation Format: Kalatu R. Davies, Abenaa Brewster, Isabelle Bedrosian, Patricia Parker, Melissa A. Crosby, Susan K. Peterson, Yu Shen, Robert Volk, Scott B. Cantor. Outcomes of contralateral prophylactic mastectomy in relation to familial history: a decision analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2574.

Surgeons' Perspectives of Contralateral Prophylactic Mastectomy.

Contralateral prophylactic mastectomy (CPM) is commonly performed for the treatment of breast cancer, despite its limited oncologic benefit. Little is known about surgeons' perceptions of performing CPM. We hypothesized that a proportion of surgeons would report discomfort with performing CPM, particularly when there is discordance between patients' perceived benefit from CPM and the expected oncologic benefit. A survey was sent to members of the American Society of Breast Surgeons seeking self-reports of surgeons' practice patterns, perceptions, and comfort levels with CPM. Of the 2436 members surveyed, 601 responded (response rate=24.7%). The median age of respondents was 52years, and 59% of responders were women. The majority (58%) reported that 80% of their practice was devoted to the treatment of breast disease. Fifty-seven percent (n=326) of respondents reported discomfort with performing CPM at some point in their practice. While most surgeons (95%) were comfortable with CPM on a patient with a deleterious BRCA mutation, only 34% were comfortable performing CPM on an average-risk patient. The most common reasons reported for surgeon discomfort with CPM were a concern for overtreatment, an unfavorable risk/benefit ratio, and inadequate patient understanding of the anticipated risks and benefits of CPM. Despite the increasing use of CPM for the treatment of breast cancer, many surgeons report discomfort with CPM. Concerns with performing CPM predominantly focus on ambiguities surrounding the oncologic benefit and relative risk of this procedure. Further research is needed to define optimal shared decision-making practices in this area.

Abstract P5-08-39: Low risk of contralateral breast cancer rates in Asian women- A case for not recommending contralateral prophylactic mastectomy

Abstract Introduction The rates of contralateral prophylactic mastectomy (CPM)appears to be higher in the west as compared to the east.1,2There is a suggestion of an improved survival benefit of CPM. 1The trends are increasing in the west and little is known in Asia. In western data a rate of 0.5 to 1% per year is often quoted. However, There is scarcity of epidemiological data on rates of contralateral breast cancer (CBC) in Asia. Known predictors of CBC in the west include high stage at diagnosis, early age at diagnosis, presence of family history, genetic predisposition, time from first diagnosis and hormone receptor status. Little is known in Asia. Population based registries are not available in Malaysia as in many Southeast Asian countries. This study aims to provide CBC rates to provide evidence for informed decision making of CPM in Asians. Method A prospective database of newly diagnosed Stage I and II breastcancer patients diagnosed in University Malaya Medical Centre between 1993 to 2012 were analysed. Data on CBC were obtained from institutional database and medical records. Multivariate analysis used Cox regression was applied to observe for any associations with multiple variables such as age at diagnosis, time from diagnosis, presence of family history, menopausal status, ethnic groups, parity and hormone status. Results A total of 3060 Stage I and II patients were prospectively followed up. 127 (4.2%) women developed contralateral breast cancer.At 5 years, 57 (1.9%) and at 10 years, 100(3.4%) developed CBC. Using a multivariate model, the only independent predictor of developing contralateral breast cancer at 5 years was a positive family history OR 1.97(CI 1.02-3.80). However, at 10 years we found the effect of positive family history diminished OR1.57 (CI 0.94-2.64) and younger women were more likely to develop cancer, those aged 51 to 64 years OR 0.29 (CI 0.11-0.73) , &amp;gt;65 years OR 0.20 (CI 0.07-0.60)compared to those less than 35 years. The other factors in the model were not significant. Discussion There is an increasing rate of CPM at 22% from 9% in the west1. A study in Singapore showed a low CPM rate of 1.25%2 . Although uptake of CPM in Asia has not been reported extensively and appears low, the trends may rise and that evidence is needed to counsel patients on the benefits and harms of CPM if patients request for CPM. Given the lower incidence of breast cancer in Malaysia ie 5% average risk compared to 10% in the west, an urgent need to document the risk of contralateral breast cancer, and this data from a single institution is the first to report this rates in Southeast Asia. Conclusion The data shows that risk of contralateral breast cancer is low in this Southeast Asian country. Any recommendations or practice of CPM should be dealt with extreme caution.

Abstract CS1-2: Contralateral prophylactic mastectomy: Patient preferences and risk perceptions

Abstract Recent studies have revealed increasing rates of contralateral prophylactic mastectomy (CPM) among women with unilateral early stage breast cancer. Bilateral mastectomy at diagnosis of unilateral breast cancer is particularly common among young women, with younger age consistently identified as a predictor of CPM. This trend for more surgery rather than less has raised concerns, given the lack of evidence for a survival benefit from CPM and the relatively low risk of contralateral breast cancer for most women in this setting. Although mastectomy is a safe procedure and major complications are rare, there are potential negative consequences including cosmetic concerns and clinically significant potential long-term sequelae such as numbness of the chest skin and chronic pain and decreased function. Given most women opt for reconstructive surgery, extended recovery time, additional surgical complications, and decreased strength or function due to muscles being moved or stretched are also additional risks. Recent data have revealed that some women who undergo CPM have misperceptions about their actual risks and the values of the prophylactic surgery. In a recent cross-sectional survey of young breast cancer survivors who had undergone bilateral mastectomy for unilateral breast cancer, most women indicated that desire to decrease their risk for contralateral breast cancer (98%) and improve survival (94%) were extremely or very important factors in their decision to have CPM. However, only 18% indicated that women with breast cancer who undergo CPM live longer than those who do not. BRCA1 or BRCA2 mutation carriers more accurately perceived their risk for contralateral breast cancer, whereas women without a known mutation substantially overestimated this risk. An increasing body of literature suggests that fear of recurrence and anxiety are strong predictors of undergoing CPM. Improved education and counseling about the risks and benefits of CPM, as well as increased awareness and management of anxiety surrounding breast cancer diagnosis and treatment, are likely to help patients to understand their risks more fully and to make decisions consistent with their preferences and values. Decision aids may be particularly useful in this setting. Citation Format: Ann Partridge. Contralateral prophylactic mastectomy: Patient preferences and risk perceptions [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr CS1-2.

P4-11-10: Perceptions, Knowledge and Satisfaction with Contralateral Prophylactic Mastectomy among Young Women with Breast Cancer.

Abstract Background: There has been an increasing prevalence of contralateral prophylactic mastectomy (CPM), particularly among younger women with breast cancer. There has been limited research evaluating patient preference, knowledge and decision-making regarding this issue. Methods: We surveyed women who had bilateral mastectomy who were enrolled in a multicenter, longitudinal cohort study of women diagnosed with breast cancer at age 40 and younger. The CPM survey included 23 items on decision making, knowledge, and satisfaction with CPM. Results: Of the 550 patients enrolled as of November 2010, 157 (28.5%) had bilateral mastectomy, of whom 124 completed the CPM survey (response rate 79%). Women with bilateral breast cancer (3) or bilateral prophylactic (1) indications for surgery were excluded. Median age at diagnosis was 37 years (range 26–40); 26 women (21%) reported having a genetic mutation (21 BRCA1 and 5 BRCA2). Excluding mutation carriers, women estimated that a median of 10 of 100 women (range 0–90) would develop contralateral breast cancer in the 5 years after unilateral breast cancer treatment and that 5 of 100 women (range 0 — 98) treated with CPM would develop contralateral breast cancer. Eighteen percent of all respondents believed that women who undergo bilateral mastectomy live longer. Women were asked the importance of potential reasons for undergoing CPM (see Table 1). Eighty-two percent of women were “extremely confident” in their decision to undergo CPM and 92% would “definitely” still choose CPM. Conclusion: Young women with breast cancer have high rates of CPM. Many young women who have undergone CPM overestimate the risk of contralateral disease and the benefits of CPM, including believing that CPM will prevent metastasis and extend life. Interventions to counsel young women with early breast cancer to help them make optimal surgical treatment decisions are needed. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-10.

Current knowledge on contralateral prophylactic mastectomy among women with sporadic breast cancer.

The use of contralateral prophylactic mastectomy (CPM) in the U.S. among patients with unilateral invasive breast cancer increased by 150% from 1993 to 2003. Although CPM has been shown to reduce the risk for developing contralateral breast cancer, there is conflicting evidence on whether or not it reduces breast cancer mortality or overall death. The increase in the CPM rate is especially concerning among women with early-stage sporadic breast cancer who have a minimal annual risk for developing contralateral breast cancer, and for many of these women the risk for distant metastatic disease outweighs the risk for contralateral breast cancer. The lack of information about the clinical value of CPM in women with sporadic breast cancer is an important public health problem. This review evaluates current data on the clinical indications for CPM and long-term patient satisfaction and psychosocial outcomes. Gaps in knowledge about the clinical value of CPM, including patient- and physician-related psychosocial factors that influence the decision-making process of CPM among women with sporadic breast cancer, are highlighted.

Patient and tumor characteristics associated with contralateral breast cancer in a nested population-based case-control study.

1014 Background: The identification of patient and tumor characteristics associated with an increased risk of contralateral breast cancer (CBC) would be useful for counseling women with unilateral breast cancer (UBC) regarding risks and benefits of contralateral prophylactic mastectomy (CPM), a procedure increasingly chosen by young women. Methods: The WECARE (Women’s Environmental Cancer and Radiation Epidemiology) study is a multicenter, population-based study of 708 cases with metachronous CBC and 1,399 matched controls with UBC nested within a cohort of 52,536 women under age 55 at diagnosis of an initial breast cancer between 1985−2000. Family history was collected by phone interviews; treatment and tumor characteristics were abstracted from medical records, and germline DNA was tested for deleterious mutations of BRCA1/2. Multivariable adjusted rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Results: The median age of cases and controls was 46. 111 cases and 74 controls carried BRCA1/2 mutations. Results are reported for non-carriers. Race, body mass index and menopausal status did not differ between cases and controls. Risk of CBC was elevated among women with a first primary with lobular histology (RR=1.5; 95% CI=1.1−2.2). Grade 2 (RR 0.6, 95% CI 0.5−0.9) and grade 3 tumors (RR 0.6, 95% CI 0.4−0.9) were associated with a lower risk of CBC compared to grade 1 tumors. ER status was not significantly associated with CBC, but only 35% of ER positive patients received tamoxifen. These results were not modified by age at diagnosis (<45, ≥45) or family history of breast cancer. The proportion of in situ CBC increased from 18.2% between 1985−1988 to 22.0% between 1997−2000 (p=0.04). Conclusions: In this large population based study, women with an initial diagnosis of lobular cancer or low grade histology were at increased risk of CBC in the absence of widespread use of endocrine therapy. Given the known benefit of endocrine therapy in reducing CBC, our findings suggest that consideration of standard tumor characteristics alone in women without BRCA1/2 mutations do not identify a subset of women likely to benefit from CPM.

Contralateral Prophylactic Mastectomy: Caveat Emptor

Contralateral Prophylactic Mastectomy: Caveat Emptor