Women's preferences for contralateral prophylactic mastectomy following unilateral breast cancer: What risk-reduction makes it worthwhile?

ObjectivesContralateral prophylactic mastectomy (CPM) reduces the risk of contralateral breast cancer (BC) following unilateral BC, but may not increase survival in BRCA1/2 mutation negative women. Despite this, and the risk for adverse physical and psychological impact, uptake is increasing in BRCA1/2 mutation negative women. We aimed to quantify the degree of reduction in lifetime contralateral BC risk women required to justify CPM, and to explore demographic, disease and psychosocial predictors of preferences using Protection Motivation Theory (PMT) as a theoretical framework. Reasoning behind preferences was also examined.Materials and methods388 women previously diagnosed with unilateral BC, of negative or unknown BRCA1/2 status, were recruited from an advocacy group research database. Two hypothetical risk trade-off scenarios were used to quantify the reduction in lifetime contralateral BC risk that women judged necessary to justify CPM, using a 5% and 20% baseline. Demographic, disease and PMT measures were assessed using a questionnaire.ResultsMost women required their risk to be more than halved from a 5% or 20% baseline to justify CPM. Polarised preferences were also common, with some women consistently accepting or refusing CPM independent of risk/benefit trade-offs. Preferences were associated with coping self-efficacy and having a prior CPM. Explanations for judging CPM worthwhile included reducing or eliminating contralateral BC risk, attaining breast symmetry and reducing worry.ConclusionRisk-reduction preferences were highly variable. Decisive factors in women's preferences for CPM related to clinical, psychological and cosmetic outcomes, but not to demographic or disease characteristics.     

Increasing trend of contralateral prophylactic mastectomy: What are the factors behind this phenomenon?

IntroductionNumerous studies have shown a trend towards increasing rates of contralateral prophylactic mastectomy (CPM) in the US. In this review, we will explore the trend, possible causative factors and outcomes from CPM.MethodsWe performed a literature review of all relevant retrospective reviews, clinical trials and review articles regarding contralateral prophylactic mastectomy.ResultsSeveral studies have noted a four to fivefold increase in CPM in recent years; an increase most notable in younger patients. When surveyed, patients report that the most important factors affecting their choice of CPM include fear of cancer recurrence, genetic counseling/testing, family history or additional high risk factors, stress surrounding close follow up, the availability of reconstructive surgery and information provided about contralateral breast cancer (CBC) risk and risk for local recurrence. Women who have undergone CPM do report high satisfaction with the procedure and some studies suggest risk reduction.ConclusionCPM rates have increased across the US and numerous factors have been reported to increase the likelihood of choosing CPM. Despite that bilateral mastectomy is associated with an increased risk of wound and overall postoperative complications for certain populations, this surgery appears to have psychological, cosmetic and possibly oncologic benefit.     

Issues of Regret in Women With Contralateral Prophylactic Mastectomies

Background: Patients with a history of carcinoma of one breast have an estimated risk of 0.5% to 0.75% per year of developing a contralateral breast cancer. This risk prompts many women to consider contralateral prophylactic mastectomy (CPM) as a preventive measure. Virtually nothing is known about patient acceptance following CPM. We have developed a National Prophylactic Mastectomy Registry comprised of a volunteer population of 817 women from 43 states who have undergone prophylactic (unilateral or bilateral) mastectomy.Methods: Of the 346 women with CPM who responded to national notices, 296 women returned detailed questionnaires. The information obtained included patient demographics, family history, reproductive history, ipsilateral breast cancer staging and treatment, as well as issues involving the CPM.Results: At median follow-up of 4.9 years, the respondents were primarily married (79%), white (97%) women who had some level of college education or above (81%). These women cited the following reasons for choosing CPM: (1) physician advice regarding the high risk of developing contralateral breast cancer (30%); (2) fear of developing more breast cancer (14%); (3) desire for cosmetic symmetry (10%); (4) family history (7%); (5) fibrocystic breast disease (4%); (6) a combination of all of these reasons (32%); (7) other (2%); and (8) unknown (1%). Eighteen of the 296 women (6%) expressed regrets regarding their decision to undergo CPM. Unlike women with bilateral prophylactic mastectomies, regrets tended to be less common in the women with whom the discussion of CPM had been initiated by their physician (5%) than in the women who had initiated the discussion themselves (8%) (P = ns). Family history and stage of index lesion had no impact on regret status. The reasons for regret included: (1) poor cosmetic result, either of the CPM or of the reconstruction (39%); (2) diminished sense of sexuality (22%); (3) lack of education regarding alternative surveillance methods or CPM efficacy (22%); and (4) other reasons (17%).Conclusions: To minimize the risk of regrets in women contemplating CPM, it is imperative that these women be counseled regarding an estimation of contralateral breast cancer risk, the alternatives to CPM, and the efficacy of CPM. In addition, these women should have realistic expectations of the cosmetic outcomes of surgery and understand the potential impact on their body image.     

Axillary metastatic disease as presentation of occult or contralateral breast cancer

IntroductionAtypical axillary metastasis may arise from an occult ipsilateral or contralateral breast cancer or from primary non-breast tumour. The treatment of this entity is challenging and presents various options. We present our experience with a brief review of the literature.ResultsA study of atypical axillary metastasis done at St Mary's hospital, from 1998 to 2008, identified six cases. Radiological investigations and immunohistochemistry excluded non-breast primary tumour. Three patients had occult breast cancer on presentation, two patients had previously treated contralateral breast cancer and one patient developed a primary metachronous contralateral breast cancer, which had a completely different histological profile from the involved lymph nodes on the same side. Axillary nodal clearance was done for all patients except for the patient with lymphoedema. Four patients were alive with no evidence of disease and two patients died of the disease at a median follow-up of 23 months.ConclusionAtypical axillary metastasis from ipsilateral occult or contralateral breast cancer should be treated with axillary node clearance and further endocrine or chemotherapy. Radiation treatment or a watchful policy to the ipsilateral breast should be validated by further studies.     

Development and pilot testing of a Decision Aid (DA) for women with early-stage breast cancer considering contralateral prophylactic mastectomy

ObjectiveDescribe the development, acceptability and feasibility of a Decision Aid (DA) for women with early-stage breast cancer (BC) at average contralateral breast cancer (CBC) risk considering contralateral prophylactic mastectomy (CPM).MethodsThe DA was developed using the International Patient Decision Aid Standards (IPDAS) and the Ottawa Decision Support Framework. It provides evidence-based information about CPM in a booklet format combining text, graphs and images of surgical options. Twenty-three women with a history of early-stage breast cancer were interviewed in person or over the phone using a ‘think aloud approach’. Framework analysis was used to code and analyse data.ResultsTwenty-three women participated in the study. Mean age of participants was 58.6 years and time since diagnosis ranged from 14 months to 21 years. Five women had CPM and eighteen had not. Women strongly endorsed the DA. Many felt validated by a section on appearance and found information on average risk of recurrence and metastases helpful, however, noted the importance of discussing personal risk with their surgeon. Many requested more information on surgery details (time taken, recovery) and costs of the different options.ConclusionThe DA was acceptable to women, including the format, content and proposed implementation strategies. Practical and financial issues are important to women in considering treatment options.Practice implicationsWomen appreciate information about CPM at diagnosis and emphasised the importance of discussing potential downsides of the procedure in addition to benefits. The DA was considered acceptable to facilitate such discussions.     

单侧乳腺癌行预防性对侧乳房切除术的研究进展

为了能够防止对侧乳腺癌的发生从而避免产生相关的治疗和死亡,越来越多的单侧乳腺癌患者接受了预防性对侧乳房切除术(CPM),CPM在高风险人群中已经被认为能够获益,比如对于绝经前的BRCA1/2基因突变携带者。目前针对BCRA基因突变接受CPM已经达成了共识.尚无法证明CPM在其他人群中的生存获益.但CPM能够减少95%发生对侧乳腺癌的风险。所以个体化地评估患者发生对侧乳腺癌的风险和合理地制定相应的手术治疗是十分重要的。本文主要综述了发生对侧乳腺癌的危險因素并且探讨单侧乳腺癌患者施行CPM的获益。     

Contralateral prophylactic mastectomy in breast cancer patients who test negative for BRCA mutations

Background

Determination of BRCA1 and 2 mutation carrier status is important. Although BRCA carriers are offered bilateral mastectomy and oophorectomy, most who test negative decline. Some women choose contralateral prophylactic mastectomy (CPM) at the time of their breast cancer diagnosis despite testing negative.

Methods

A total of 110 women with breast cancer received genetic testing before surgical treatment. Patient demographics, tumor characteristics, surgical treatment, and magnetic resonance imaging use were recorded.

Results

Results revealed BRCA1/2 mutation in 33%, variant of unknown significance in 6%, and no mutation in 61% of women. In BRCA-negative women, 37% chose CPM. Marital status was significant for CPM (P = .03). Race, age, stage of presentation, and biomarker status were not associated with choice of CPM. Ninety-six percent of CPM recipients underwent breast reconstruction. Magnetic resonance imaging use did not affect CPM rates (P = .99).

Conclusions

Increased rates of CPM have been observed. In our study married women were more likely to choose CPM. We recommend genetic genotyping before surgery. These findings warrant further investigation.     

Review of risk factors for the development of contralateral breast cancer

Background

Women treated for breast cancer have an increased risk for developing metachronous contralateral breast cancer (CBC). Patient perception of this risk is often overestimated and has been found to contribute to the decision to undergo contralateral prophylactic mastectomy. An individual's risk is dependent on both patient and tumor characteristics. This review examines and summarizes the current literature on the factors that affect CBC risk.

Data Sources

English-language publications with the keyword “contralateral breast cancer” were identified through a MEDLINE literature search.

Conclusions

The global incidence of CBC is decreasing, a trend that is attributed to more effective adjuvant therapies. Patients with BRCA germ-line mutations demonstrate the highest risk for CBC. In the absence of known genetic mutations, patients with strong family histories who are diagnosed at young ages (<35 years) with estrogen receptor–negative index tumors appear to have a higher incidence of CBC.     

Cáncer de mama contralateral y recurrencia en portadoras BRCA1/2 y no portadoras con alto riesgo de cáncer de mama hereditario tras mastectomía bilateral

IntroductionContralateral prophylactic mastectomy (CPM) has been reported to reduce risk of contralateral breast cancer (CBC) by at least 90%.In addition, BRCA carriers presents higher risk of ipsilateral recurrence and a second primary tumor.The aim is to evaluate risk of CBC and recurrence and to analyze predictive factors in BRCA1/2 mutation carriers and non-carriers at high-risk of hereditary breast cancer patients.MethodsRetrospective observational study. 46 patients underwent bilateral mastectomy during 2004-2018.ResultsCohort comprised 9 patients BRCA1,12 BRCA2 and 25 at high-risk without mutation. Median follow-up 79 months. 16 patients recently diagnosed and 30 previously treated by breast cancer whom underwent CPM at second time (because of later detection of BRCA mutation in 10 cases). The external lateral incision was most frequent surgical technique. In all patients immediate reconstruction was performed.In CPM pieces, 4 in situ carcinoma, 3 invasive and 1 atypical hyperplasia were found. The incidence of occult contralateral cancer was 15.2%. Recurrence was observed in 5 patients a media of 21.2 months after surgery. FSD was 83.74 months and OS 84.33 months. Regression models identified BRCA1/2 mutation and high risk without mutation as significant occult tumor predictive factors while tumor size ≥ 2 cm was predictive of recurrence.ConclusionsIn our series we found a10.8% recurrence despite CPM and 7 patients (15.2%) would have developed a CBC in subsequent years.     

HER2阳性早期乳腺癌治疗年度进展

临床治疗指南推荐曲妥珠单抗作为HER2+早期乳腺癌的标准辅助治疗手段之一。在此基础之上,研究者继续尝试新的突破:一方面部分研究者试图通过双靶向治疗、延长用药期限等手段,进一步降低HER2+早期乳腺癌复发率;另一方面,其他研究者也在尝试缩短靶向治疗时间、减少传统化疗药物的使用等,以减少不必要的治疗及其带来的毒副作用。本文将对近期大型临床研究结果进行总结,围绕四个关于早期乳腺癌抗HER2辅助治疗的热点问题:HER2低表达患者是否需要抗HER2治疗?能否缩短抗HER2治疗的疗程?是否需要加强HER2+早期乳腺癌的靶向治疗?是否可以减少化疗药物的使用?为临床医生合理选择抗HER2靶向治疗提供参考。     

Breast cancer in women at high risk: The role of rapid genetic testing for BRCA1 and -2 mutations and the consequences for treatment strategies

Specific clinical questions rise when patients, who are diagnosed with breast cancer, are at risk of carrying a mutation in BRCA1 and -2 gene due to a strong family history or young age at diagnosis. These questions concern topics such as 1. Timing of genetic counseling and testing, 2. Choices to be made for BRCA1 or -2 mutation carriers in local treatment, contralateral treatment, (neo)adjuvant systemic therapy, and 3. The psychological effects of rapid testing. The knowledge of the genetic status might have several advantages for the patient in treatment planning, such as the choice whether or not to undergo mastectomy and/or prophylactic contralateral mastectomy. The increased risk of developing a second breast cancer in the ipsilateral breast in mutation carriers, is only slightly higher after primary cancer treatment, than in the general population. Prophylactic contralateral mastectomy provides a substantial reduction of contralateral breast cancer, although only a small breast cancer specific survival benefit. Patients should be enrolled in clinical trials to investigate (neo)-adjuvant drug regimens, that based on preclinical and early clinical evidence might be targeting the homologous recombination defect, such as platinum compounds and PARP inhibitors. If rapid testing is performed, the patient can make a well-balanced decision. Although rapid genetic counseling and testing might cause some distress, most women reported this approach to be worthwhile. In this review the literature regarding these topics is evaluated. Answers and suggestions, useful in clinical practice are discussed.     

Contralateral axillary nodal involvement from invasive breast cancer

Metastatic breast cancer to the contralateral axilla (CAM) is defined as stage IV disease. We postulate that CAM represents an extension of local-regional disease rather than distant metastasis and may have a better outcome. A single-institution, retrospective review of breast cancer cases from January 2005 and May 2011 was performed to identify cases with CAM. Eligibility for the study included unilateral primary breast cancer at presentation with synchronous/metachronous documented CAM without a documented primary invasive breast cancer within the contralateral breast by surgery or MRI. Clinicopathologic data was recorded for these patients (pts). Thirteen pts were identified. 12/13 (92%) pts presented with a locally advanced breast tumor or an ipsilateral in-breast recurrence. 10/13 (77%) pts had documented dermal involvement of tumor either at initial presentation or local recurrence. CAM occurred synchronously with the initial primary tumor (5 pts, 38%), concomitant with a local recurrence (5 pts, 38%), metachronously with the initial tumor (1 pt, 8%), and metachronously with a local recurrence (2 pts, 15%). Three patients had other distant disease at presentation. Of the other 10 pts, seven developed distant disease with a mean follow up of 3.6 years (range 0.3–7.6 years). Three pts have no evidence of disease at a mean follow up of 5.8 years (range 1.5–8.2). CAM may have different prognostic implications than other distant metastases and may occur through dermal lymphatic spread. Further study is warranted on the prognosis and management of these challenging and rare cases.     

Breast magnetic resonance imaging for preoperative locoregional staging

BACKGROUND: Breast magnetic resonance imaging (MRI) has been recommended increasingly in the preoperative setting for patients newly diagnosed with malignancy to evaluate tumor extent, multicentricity, and contralateral disease. METHODS: Results of conventional imaging, breast MRI, and pathology were analyzed from 603 consecutive breast cancer patients who underwent MRI preoperatively. The focus of this retrospective study was imaging-histologic correlation. RESULTS: Reoperation for positive margins after lumpectomy occurred in 8.8% of patients. Multicentricity was identified by MRI alone in 7.7% of patients, whereas 3.7% were found to have contralateral cancer by MRI. The sensitivity of MRI was 93% in detecting multicentric disease and 88% for contralateral disease, whereas sensitivity for conventional imaging was 46% and 19%, respectively. Unsuspected disease was identified by MRI equally for invasive ductal and ductal carcinoma in situ histology, whereas multicentricity was found more frequently with invasive lobular carcinoma. CONCLUSIONS: Breast MRI is recommended for preoperative evaluation of the newly diagnosed breast cancer patient.     

Contralateral mastoplasty for breast reconstruction: A good opportunity for glandular exploration and occult carcinomas diagnosis

Background: Exploration of the contralateral breast in case of breast cancer has been advocated by many investigators, based on the incidence of contralateral cancer expected to be around 10–15%. Method: From 1978 to 1993, 813 contralateral mammaplasties were performed to obtain symmetry in the course of breast reconstruction, including 373 mastopexies and 440 reduction mammaplasties (RMs). All these operations were performed in patients treated for a cancer of the opposite breast. Clinical and radiologic examination before the reduction mammaplasty showed tissue to be free of evident tumor. Results: Twenty clinically and radiologically occult contralateral cancers were found in the reduction specimen (4.6%). Most of them were located in the lower and central quadrants (70%). The macroscopic size of the tumors varied from 3 to 16 mm. Twelve carcinomas were in situ, and eight cases were infiltrating. Conclusion: The symmetry procedure allows a good check-up of the glandular tissue of the contralateral breast at the time of the breast reconstruction, especially when there is no evidence of tumor. The different techniques of breast reduction provide specific possibilities for such exploration and should be chosen according to the preferential area that should be explored.     

Is Routine Sentinel Lymph Node Biopsy Indicated in Women Undergoing Contralateral Prophylactic Mastectomy? Magee-Womens Hospital Experience

INTRODUCTION: The routine use of sentinel node biopsy (SLNB) at the time of prophylactic mastectomy remains controversial. This retrospective study was undertaken to determine if SLNB is justified in patients undergoing CPM. METHODS: Between 1999 and 2004, 155 patients underwent contralateral prophylactic mastectomy (CPM) at the Magee-Womens Hospital of University of Pittsburgh Medical Center. Eighty patients (51.6%) had SLNB performed at the time of CPM. The therapeutic mastectomy and the CPM specimens were evaluated for histopathology. Goldflam's classification was used to determine the risk of malignancy in the CPM specimens. RESULTS: Pathology in the therapeutic mastectomy specimens included 105 (68%) invasive carcinomas and 50 (32%) in-situ carcinomas. Multicentricity and/or multifocality were reported in 49.7%, and 70% were estrogen receptor positive. Two invasive breast cancers and three cases of DCIS were diagnosed in 155 CPM specimens (n = 5, 3.2%). The median number of SLN identified was 2 (range 1-6) from the CPM axilla. Two patients had positive SLNB for metastatic carcinoma (n = 2/80, 2.5%) with no primary tumor identified in the prophylactic mastectomy specimen. In both patients the therapeutic mastectomy was for recurrent invasive carcinoma in patients with a prior history of axillary node dissection. Occult carcinoma was found in five prophylactic mastectomy specimens: two invasive and three DCIS. Only 1 out of the 75 patients not undergoing SLNB at the time of their initial surgery would have required axillary staging for a previously undiagnosed invasive cancer in the CPM specimen on final pathology. Of all 155 patients undergoing CPM, only 4 (2.5%) had identified final pathologic findings where axillary staging with SLNB was beneficial. There was no evidence of arm lymphedema in any patient who had undergone CPM and SLNB at a median follow-up of 24 months. CONCLUSION: Although SLNB is a minimally invasive method of axillary staging, this retrospective study does not support its routine use in patients undergoing CPM.     

A standard mastectomy should not be the only recommended breast surgical treatment for non-metastatic inflammatory breast cancer: A large population-based study in the Surveillance,Epidemiology, and End Results database 18

BackgroundStandard mastectomy has long been the recommended breast surgical treatment for non-metastatic inflammatory breast cancer (IBC). The objective of this population-based study was to evaluate the significance of various breast surgical treatments for this highly aggressive subtype.MethodsThe Surveillance, Epidemiology, and End Results program registry was searched to identify women with non-metastatic IBC receiving standard treatment including breast surgery, radiation therapy and chemotherapy diagnosed between 1998 and 2013. Comparisons of the proportions of various breast surgery procedures over the years were performed using Pearson's chi-square test. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. Cox models were then fitted to compare the association between various breast surgical procedures and BCSS or OS after adjusting for patient and tumor characteristics.ResultsA total of 3374 cases were identified. Over the years, the proportion of contralateral prophylactic mastectomy (CPM), breast reconstruction and both were increasing. The proportion of implant-based reconstruction was also increasing with no difference in survival compared with other types of reconstruction. There was no statistically significant difference in BCSS or OS among various breast surgery treatments, such as breast conserving surgery, CPM, breast reconstruction and standard unilateral mastectomy.ConclusionsBreast surgery is of great significance to the clinical outcome of IBC. Standard mastectomy should not be the only recommended breast surgical treatment.     

Options in Breast Cancer Local Therapy: Who Gets What?

Today, women with primary breast cancer may consider three surgical options: breast-conserving surgery (BCS), mastectomy (MT), and mastectomy with contralateral prophylactic mastectomy (MT?+?CPM). In each case, the ipsilateral axilla is generally managed with a sentinel node biopsy and possibly an axillary lymph node dissection. BCS generally requires breast radiotherapy, except in older women having tumors with a favorable prognosis who will receive endocrine therapy. In contrast, women treated with MT generally do not require radiotherapy, except for those with large tumors or metastases to the axillary nodes. Moreover, MT and MT?+?CPM are usually undertaken with breast reconstruction. Yet, most patients today are suitable candidates for BCS, with a few relative contraindications. Thus, early pregnancy, previous radiotherapy to the breasts, active collagen vascular disease, multicentric breast cancer, large tumors (although neoadjuvant systemic therapy can often reduce tumor size), and the presence of the BRCA mutation are all relative contraindications to BCS. BRCA mutation carriers should consider MT?+?CPM because their risk of contralateral breast cancer is greatly increased. In the U.S., the use of MT for the treatment of primary breast cancer has declined in recent years, while MT?+?CPM rates have increased, and BCS rates have remained relatively stable. The underlying reasons for these trends are not fully understood. Local therapy options should be discussed with each patient in considerable detail, and more studies are needed to better elucidate which factors influence a woman's choice of local therapy following a breast cancer diagnosis.     

Incidence and outcomes of contralateral breast cancers

BACKGROUND: The significance of a contralateral breast cancer is largely unknown, making prophylactic mastectomy controversial. METHODS: Differences between stages of initial and contralateral cancers were determined by t test. Survival distributions were compared by log-rank analyses and compared with Surveillance Epidemiology and End Results data for unilateral cancers. RESULTS: Metachronous contralateral cancers occurred at a rate of .13% per year and were of significantly lower stage. Metachronous cancers adversely impacted survival for patients with low-stage initial cancers, but the interval between cancers was less than 36 months. Synchronous tumors occurred in 2.3% of patients; survival was worse than for patients with metachronous cancers. CONCLUSIONS: Prophylactic mastectomy is unlikely to be beneficial because of the lower stages and low incidence of second cancers, even for patients with initial low-stage cancers.     

Perceptions of Contralateral Breast Cancer: An Overestimation of Risk

Introduction  

The rate of contralateral prophylactic mastectomy (CPM) has recently increased. The aim of this study is to assess perceptions of contralateral breast cancer (CBC) risk among breast cancer patients and to evaluate tumor and patient factors associated with risk perception.