Timing of genetic testing in BRCA1/2 and PALB2-Associated breast cancer: Preoperative result disclosure increases uptake of risk-reducing mastectomy and reduces unnecessary exposure to radiotherapy.

INTRODUCTION: The impact of timing of genetic testing on uptake of risk reducing mastectomy (RRM) in affected female BRCA1/2 or PALB2 carriers remains an area of evolving interest, particularly with the introduction of mainstream genetic testing initiatives. METHODS: Women with stage I-III breast cancer and a confirmed germline pathogenic variant in BRCA1/2 or PALB2 between 2000 and 2023 were identified from an institutional genetics database. Uptake of RRM was evaluated according to disclosure of genetic testing results before or after index surgery for a first diagnosis of breast cancer. RESULTS: The cohort included 287 female BRCA1/2 or PALB2 carriers with a median age of 44 years (IQR, 36-52). Overall, 155 (54 %) carriers received genetic testing results before and 132 (46 %) after index breast surgery. Receipt of genetic testing results before surgery was associated with a higher rate of index bilateral mastectomy (58.7 % vs. 7.6 %, p < 0.001) and a commensurate decrease in adjuvant radiation (41.9 % vs. 74.2 %, p < 0.001). At a median follow up of 4.4 years after genetic testing, 219 (76.3 %) affected carriers had undergone bilateral RRM, including 83.9 % with preoperative knowledge and 67.4 % of patients with postoperative knowledge of their germline pathogenic variant (log rank, p < 0.001). On multivariate regression, disclosure of genetic testing results before index breast surgery was independently associated with long-term uptake of bilateral mastectomy (HR 1.69, 95 % CI 1.21-2.38). CONCLUSION: Genetic testing results delivered prior to index breast surgery increase uptake of bilateral RRM in affected BRCA1/2 and PALB2 carriers. Efforts to mainstream genetic testing would help optimize surgical decision-making.

Are There Disparities in Breast Reconstruction After Contralateral Prophylactic Mastectomy?

INTRODUCTION: Despite national guidelines against contralateral prophylactic mastectomy (CPM) in low- to moderate-risk breast cancer, CPM use continues to rise. Breast reconstruction improves health-related quality of life and satisfaction among women undergoing mastectomy. Given the lack of data regarding factors associated with reconstruction after CPM and the known benefits of reconstruction, we sought to investigate whether disparities exist in receipt of reconstruction after CPM. METHODS: The 2004-2017 National Cancer Database was queried to identify women diagnosed with breast cancer who underwent unilateral mastectomy with CPM. Patients were divided into two groups: those who underwent planned reconstruction at any timepoint and those who did not. A secondary analysis comparing types of reconstruction (tissue, implant, combined) was conducted. Patient, tumor, and demographic characteristics were analyzed using chi-square test and odds ratios were calculated using generalized estimating equations. RESULTS: The cohort included 1,73,249 women: 95,818 (55.3%) underwent reconstruction and 77,431 (45.7%) did not. Both the rate CPM and the proportion of women undergoing reconstruction after CPM increased between 2004 and 2017. Of the women who had reconstruction, 40,840 (51.7%) received implants, 29,807 (37.7%) had tissue, and 8352 (10.6%) had combined reconstruction. After adjusted analysis, factors associated with reconstruction were young age, Hispanic ethnicity, private insurance, and living in an area with the highest education and median income (P < 0.01). Patients who underwent reconstruction were less likely to have radiation (P < 0.01) and chemotherapy (P < 0.01), more likely to have stage I disease (P < 0.01), and to be treated at an integrated cancer center (P < 0.01). CONCLUSIONS: Reconstruction after CPM is disproportionately received by younger women, Hispanics, those with private insurance, and higher socioeconomic status and education. While the rate of reconstruction after CPM is increasing, there remain significant disparities. Conscious efforts must be made to eliminate these disparities, especially given the known benefits of reconstruction after mastectomy.

Breast Cancer Screening and Prophylactic Mastectomy for High-Risk Women in Romania.

Breast cancer remains a significant contributor to morbidity and mortality within oncology. Risk factors, encompassing genetic and environmental influences, significantly contribute to its prevalence. While germline mutations, notably within the BRCA genes, are commonly associated with heightened breast cancer risk, a spectrum of other variants exists among affected individuals. Diagnosis relies on imaging techniques, biopsies, biomarkers, and genetic testing, facilitating personalised risk assessment through specific scoring systems. Breast cancer screening programs employing mammography and other imaging modalities play a crucial role in early detection and management, leading to improved outcomes for affected individuals. Regular screening enables the identification of suspicious lesions or abnormalities at earlier stages, facilitating timely intervention and potentially reducing mortality rates associated with breast cancer. Genetic mutations guide screening protocols, prophylactic interventions, treatment modalities, and patient prognosis. Prophylactic measures encompass a range of interventions, including chemoprevention, hormonal inhibition, oophorectomy, and mastectomy. Despite their efficacy in mitigating breast cancer incidence, these interventions carry potential side effects and psychological implications, necessitating comprehensive counselling tailored to individual cases.

Construction and Validation of a Nomogram Predicting the Overall Survival Benefit of Unilateral Breast Cancer Patients Undergoing Contralateral Prophylactic Mastectomy.

BACKGROUND: Currently, research on the prognostic factors of unilateral breast cancer (UBC) patients receiving contralateral prophylactic mastectomy (CPM) is limited. This study aimed to construct a new nomogram to predict these patients' overall survival (OS). METHODS: In this retrospective study, 88,477 patients who underwent CPM or unilateral mastectomy (UM) were selected from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier curves and Cox regression analyses were used to determine the difference in the impact of the 2 surgical methods on the prognosis. Multivariate Cox analysis was used to determine the best prognostic variable and construct a nomogram. The concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the discrimination capability and clinical effectiveness of the nomogram. RESULTS: The prognosis of patients receiving CPM and UM was significantly different. The DCA curves indicated that the nomogram could provide more excellent clinical net benefits for these patients. The NRI and IDI of the nomogram demonstrated that its performance was better than that of the classical tumor-node-metastasis (TNM) staging system. CONCLUSION: This study developed and validated a practical nomogram to predict the OS of UBC patients undergoing CPM, which provided a beneficial tool for clinical decision-making management.

The impact of prophylactic mastectomy on sexual well-being: a systematic review.

INTRODUCTION: Considering the increasing women's awareness of health promotion and disease prevention programs, mutation carriers are inevitably asked to face important decisions concerning the possibility of undergoing prophylactic mastectomy. Risk-reducing mastectomy (RRM) has become increasingly more common, although it has a significant impact on women's quality of life and sexual well-being. OBJECTIVES: The systematic review aims to evaluate the impact of RRM on the sexuality of women with breast cancer. METHODS: According to Cochrane Collaboration guidelines and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, the study quantified the effects of frontline work on the mental health of healthcare workers. This review followed the PRISMA guidelines. Three databases were systematically searched from inception to December 2022. The expression ("sexuality" OR "sexual" OR "sex") AND ("prophylactic mastectomy" OR "risk-reducing mastectomy") was searched in PubMed, Ovid Medline, and Embase. Twenty-two articles published in English until 2022 were selected. RESULTS: Two studies investigated sexual experience after risk-reducing surgeries as a single outcome, while other studies analyzed the relationship between sexuality and psychosocial outcomes, risk perception, and satisfaction. In all of the included studies, significant findings in sexual dysfunction were found. The most reported problems were related to sexual satisfaction and attractiveness, body image, and loss of femininity. Last, women reported changes in the relationship with their partners. CONCLUSION: RRM has a major impact on body image that affects sexual functioning and quality of life. These implications must be considered during treatment selection.

Symmetric Breast Surgery: Balancing Procedures versus Prophylactic Mastectomy and Immediate Reconstruction.

BACKGROUND: Various techniques for management of the contralateral breast exist in patients with unilateral breast cancer, including contralateral prophylactic mastectomy with immediate breast reconstruction (PMIBR), and symmetrization techniques including augmentation, reduction, or mastopexy. The purpose of this prospective cohort study was to evaluate and compare complications and patient-reported satisfaction of patients with contralateral PMIBR versus having symmetrization procedures. METHODS: A 7-year, single-institution, prospectively maintained database was reviewed. Patient-reported BREAST-Q scores were obtained at baseline, 3 months, and 12 months prospectively. Postoperative complications, oncologic outcomes, and BREAST-Q scores were compared. RESULTS: A total of 249 patients were included, 93 (37%) of whom underwent contralateral PMIBR and 156 (63%) of whom underwent contralateral symmetrization. The patients who underwent PMIBR were younger and had less comorbidities compared with patients with symmetrization. Rates of major and minor complications were similar, apart from higher rates of minor wound dehiscence in the PMIBR group. When comparing mean change at 12-month follow-up to preoperative results, there was a significant decrease in physical well-being of the chest in the symmetrization compared with the PMIBR group (2.94 versus -5.69; P = 0.042). There were no significant differences in mean breast satisfaction and psychosocial well-being, and nonsignificant decreases in sexual well-being between groups. CONCLUSIONS: Patients with unilateral breast cancer who underwent immediate contralateral breast management, with either contralateral PMIBR or symmetrization techniques, demonstrated similar profiles of major complications and good overall satisfaction except for one physical well-being domain. Management of the contralateral breast with symmetrization may provide similar outcomes compared with PMIBR, which often is considered not necessary in patients without specific indications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Low Cancer Occurrence Rate following Prophylactic Nipple-Sparing Mastectomy.

BACKGROUND: Nipple-sparing mastectomy (NSM) has become widely available for breast cancer prophylaxis. There are limited data on its long-term oncologic safety. The objective of this study was to determine the incidence of breast cancer in patients who underwent prophylactic NSM. METHODS: All patients undergoing prophylactic NSM at a single institution from 2006 through 2019 were retrospectively reviewed. Patient demographic factors, genetic predispositions, mastectomy specimen pathology, and oncologic occurrences at follow-up were recorded. Descriptive statistics were performed where necessary to classify demographic factors and oncologic characteristics. RESULTS: A total of 871 prophylactic NSMs were performed on 641 patients, with median follow-up of 82.0 months (standard error 1.24). A total of 94.4% of patients ( n = 605) underwent bilateral NSMs, although only the prophylactic mastectomy was considered. The majority of mastectomy specimens (69.6%) had no identifiable pathology. A total of 38 specimens (4.4%) had cancer identified in mastectomy specimens, with ductal carcinoma in situ being the most common (92.1%; n = 35). Multifocal or multicentric disease was observed in seven cases (18.4%) and lymphovascular invasion was identified in two (5.3%). One patient (0.16%), who was a BRCA2 variant carrier, was found to have breast cancer 6.5 years after prophylactic mastectomy. CONCLUSIONS: Overall primary oncologic occurrence rates are very low in high-risk patients undergoing prophylactic NSM. In addition to reducing the risk of oncologic occurrence, prophylactic surgery itself may be therapeutic in a small proportion of patients. Continued surveillance for these patients remains important to assess at longer follow-up intervals. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

Examining Race and Patient-Reported Outcomes After Contralateral Prophylactic Mastectomy with Reconstruction.

BACKGROUND: Little is known regarding racial differences in satisfaction and quality of life (QOL) after contralateral prophylactic mastectomy (CPM). In this study, we aim to characterize associations between race, and postoperative satisfaction and well-being, utilizing the validated BREAST-Q patient-reported outcome measure. PATIENTS AND METHODS: Patients were eligible if they were diagnosed with stage 0-III unilateral breast cancer and underwent mastectomy with immediate reconstruction at our institution between 2016 and 2022. BREAST-Q surveys were administered in routine clinical care preoperatively and postoperatively to assess QOL. We assessed whether the relationship between race, and domains of satisfaction with breasts and psychosocial well-being differed by receipt of CPM compared with unilateral mastectomy at 6 months, 1 year, 2 years, and 3 years following reconstruction. RESULTS: Of 3334 women, 2040 (61%) underwent unilateral mastectomy and 1294 (39%) underwent CPM. Compared with White and Asian women who received CPM, Black women who underwent CPM were more likely to have higher BMI (p < 0.001), undergo autologous reconstruction (p = 0.006), and receive postmastectomy radiation (PMRT) (p < 0.001). There was no association between race and domains of satisfaction of breasts or psychosocial well-being for women who underwent unilateral mastectomy (p = 0.6 and p > 0.9, respectively) or CPM (p = 0.8 and p = 0.9, respectively). PMRT was negatively associated with both satisfaction with breasts (p < 0.001) and psychosocial well-being (p = 0.007). CONCLUSIONS: Differences in satisfaction with breasts and psychosocial well-being at 3-year follow-up were not associated with race but rather treatment variables, particularly the receipt of PMRT. Further investigations with a larger and more diverse population are needed to validate these findings.

Trends of incidence and mortality in metaplastic breast cancer and the effect of contralateral prophylactic mastectomy: A population-based study.

INTRODUCTION: Metaplastic breast cancer (MBC) is considered rare and aggressive. We examined the epidemiology of and prognostic factors for MBC and investigated the effect of contralateral prophylactic mastectomy (CPM), because neither had been thoroughly examined previously. METHODS: We obtained data from the Surveillance, Epidemiology, and End Results (SEER)-18(2000-2018) for epidemiological and survival analysis. RESULTS: The age-adjusted incidence per 100,000 persons of MBC increased significantly from 0.12 to 0.35 [annual percent change (APC):2.95%, 95% confidence interval [CI], 1.73-4.19]. The incidence-based mortality increased from 0.01 to 0.12 (APC: 5.01%, 95% CI: 2.50-7.58). The incidence of MBC patients who underwent CPM significantly increased from 0.003 to 0.039 with an APC of 10.96% (95%CI, 7.26-14.78). Older patients and those with higher T classification were less likely to receive CPM. The multivariate Cox model showed that CPM was not an independent predictor of good prognosis for both overall survival (OS) and breast cancer-specific survival (BCSS) (pre-propensity score matching (PSM): OS: P = 0.331; BCSS: P = 0.462. post-PSM: OS: P = 0.916; BCSS: P = 0.967). Subgroup analysis showed that CPM still did not provide a survival benefit to any risk groups. CONCLUSION: In this study, we demonstrated that the incidence and incidence-based mortality of MBC have increased over the past decades. Although the number of MBC patients who underwent CPM has significantly increased recently, CPM did not confer a survival benefit compared with unilateral mastectomy, indicating that the decision to undergo CPM should be considered carefully.

Patient-reported outcomes in bilateral prophylactic mastectomy with breast reconstruction: A narrative review.

In women at high risk of developing breast cancer, bilateral prophylactic mastectomy (BPM) 1 significantly reduces the risk; simultaneously, breast reconstruction preserves body integrity. Given the complex and personal nature of such surgical procedures, patient assessment of satisfaction and health-related quality of life (HRQoL) 2 is essential in evaluation of surgical outcomes. With this review, we aim to organize the current knowledge on patient-reported outcomes (PROs) 3 in bilateral prophylactic surgery. Literature search was conducted using the databases Google Scholar, PubMed, and Web of Science to address the following questions, which can help clinicians and women undergoing the procedures navigate their healthcare decision-making process: How does BPM with reconstruction influence cancer-related distress? How does the surgery impact patient satisfaction and HRQoL? How do preoperative PROs differ from postoperative outcomes? Does the type of BPM and the type of reconstruction impact patient satisfaction and HRQoL? Furthermore, we summarize available patient-reported outcome measures (PROMs) 4 that can be administered to women undergoing BPM with reconstruction. In addition, we discuss possible future directions for PRO research in prophylactic breast surgery.

Assessment of the effect of the American Society of Breast Surgery guidelines on contralateral prophylactic mastectomy rates for unilateral breast cancer.

BACKGROUND: In July 2016, the American Society of Breast Surgeons published guidelines discouraging contralateral prophylactic mastectomy for average-risk women with unilateral breast cancer. We incorporated these into practice with structured patient counseling and aimed to assess the effect of this initiative on contralateral prophylactic mastectomy rates. METHODS: We evaluated female patients with unilateral breast cancer undergoing mastectomy at our institution from January 2011 to November 2022. Variables associated with contralateral prophylactic mastectomy and trends over time were analyzed using the Wilcoxon rank sum test or χ2 analysis as appropriate. RESULTS: Among 3,208 patients, (median age 54 years) 1,366 (43%) had a unilateral mastectomy, and 1,842 (57%) also had a concomitant contralateral prophylactic mastectomy. Across all patients, contralateral prophylactic mastectomy rates significantly decreased post-implementation from 2017 to 2019 (55%) vs 2015 to 2016 (62%) (P = .01) but increased from 2020 to 2022 (61%). Immediate breast reconstruction rate was 70% overall (81% with contralateral prophylactic mastectomy and 56% without contralateral prophylactic mastectomy, P < .001). Younger age, White race, mutation status, and earlier stage were also associated with contralateral prophylactic mastectomy. Genetic testing increased from 27% pre-guideline to 74% 2020 to 2022, as did the proportion of patients with a pathogenic variant (4% pre-guideline vs 11% from 2020-2022, P < .001), of whom 91% had a contralateral prophylactic mastectomy. Among tested patients without a pathogenic variant and patients not tested, contralateral prophylactic mastectomy rates declined from 78% to 67% and 48% to 38% pre -and post-guidelines, respectively, P < .001. CONCLUSION: Implementation of specific patient counseling was effective in decreasing contralateral prophylactic mastectomy rates. While recognizing that patient choice plays a significant role in the decision for contralateral prophylactic mastectomy, further educational efforts are warranted to affect contralateral prophylactic mastectomy rates, particularly in the setting of negative genetic testing.

Contralateral prophylactic mastectomy: Weighing the risks of delayed chemotherapy, radiotherapy, and hormonal therapy.

BACKGROUND: Many patients with unilateral breast cancer opt for contralateral prophylactic mastectomy (CPM) at the time of therapeutic mastectomy (immediate CPM) or following completion of adjuvant therapy. Studies show that immediate CPM increases the risk of surgical complications related to unilateral mastectomy (UM) alone, which may lead to delays in adjuvant therapy initiation. However, it is unclear if these complications cause clinically significant delays in initiating adjuvant chemotherapy, radiotherapy, or hormonal therapy. METHODS: A retrospective chart review was conducted on patients with breast cancer who underwent immediate CPM versus UM alone at Columbia University Medical Center from January 2000 to December 2020. Patient demographic and oncologic characteristics; complications; and timing of adjuvant chemotherapy, radiotherapy, and/or hormonal therapy relative to therapeutic mastectomy were collected. RESULTS: In this study, 239 UM alone patients were propensity score matched to 239 immediate CPM patients. No significant difference in complication rates was found between the index and contralateral breasts in CPM patients. A similar percentage of CPM and UM patients experienced postoperative complications (19% vs. 17%, p = 0.64). No significant difference in time to adjuvant chemotherapy, radiotherapy, or hormonal therapy was found between CPM patients with complications and all CPM patients or all UM patients. CONCLUSIONS: There is a lack of clear guidance for clinical decision-making regarding timing of CPM relative to adjuvant therapy. Our study suggests that immediate CPM does not significantly increase the risks of postoperative complications or complication-related delays in the initiation of adjuvant chemotherapy, radiotherapy, or hormonal therapy. This information may help patients and providers to plan, select, and schedule breast cancer treatment options.

Influence of contralateral prophylactic mastectomy on textbook outcome attainment at time of mastectomy.

INTRODUCTION: The objective of this study was to determine the incidence of textbook oncologic outcome (TOO) and its impact on overall survival (OS) among patients with invasive ductal carcinoma (IDC) following modified radical mastectomy (MRM) versus MRM with contralateral prophylactic mastectomy (MRM â€‹+ â€‹CPM). METHODS: The 2004-2017 National Cancer Database was queried for patients with IDC who underwent MRM and MRM â€‹+ â€‹CPM. TOO was defined as: resection with negative margins, adequate lymphadenectomy, length of stay ≤50th percentile, and no 30-day readmission or mortality. RESULTS: 87,573 patients were identified, of which 14.3% underwent MRM â€‹+ â€‹CPM. Logistic regression models revealed that MRM â€‹+ â€‹CPM is independently associated with a reduced likelihood of achieving TOO (AOR â€‹= â€‹0.71; P â€‹< â€‹0.001). MRM patients who achieved TOO had a higher median OS compared to those who did not (164.6 vs.142.2 months, P â€‹< â€‹0.001). CONCLUSIONS: MRM â€‹+ â€‹CPM is associated with a lower incidence of TOO attainment compared to MRM.

Top Breast Oncology Articles from 2021 to Inform Your Cancer Practice.

Breast oncology generates extensive literature and widespread media attention every year because of the high worldwide burden of this disease and also because of the rapid pace at which treatment advances have progressed. The year 2021 was no different, and this review will summarize some of the practice-changing, practice-validating, and practice-challenging publications of that year. These studies cover a broad range of topics including multidisciplinary care with gene expression profiling; breast cancer disparities; breast cancer screening; and prophylactic mastectomy surgery.

Association of Moderate-Risk Breast Cancer Genes with Contralateral Prophylactic Mastectomy and Bilateral Disease.

BACKGROUND: The impact of ATM, CHEK2, and PALB2, the three most prevalent moderate-risk breast cancer genes, on surgical decision making is not well known. METHODS: Our retrospective study included patients with resectable non-metastatic breast cancer who underwent multigene panel testing between July 2014 and January 2020 with at least one genetic alteration (pathogenic or variant of uncertain significance [VUS] in ATM [n = 49], CHEK [n = 57], or PALB2 [n = 27]). Our objectives were to determine the rate of contralateral prophylactic mastectomy (CPM) and the rate of bilateral breast cancer. Univariable analyses (UVA) and multivariable analyses (MVA) were performed to identify factors associated with CPM and bilateral breast cancer. RESULTS: The rate of CPM was 39% (n = 49/127), with 54% (n = 25/46) of patients with a pathogenic mutation and 30% (n = 24/81) of patients with a VUS choosing CPM. On MVA, premenopausal status (odds ratio [OR] 3.46) and a pathogenic alteration (OR 3.01) were associated with increased use of CPM. Bilateral disease was noted in 16% (n = 22/138). Patients with pathogenic mutations had a 22% (n = 11/51) incidence of bilateral breast cancer, while patients with VUS had a 13% (n = 11/87) incidence, although this was not statistically significant on UVA or MVA. On MVA, premenopausal status was associated with a decreased risk of bilateral disease (OR 0.33, p = 0.022). During follow-up, a breast cancer event occurred in 16% (n = 22/138). CONCLUSIONS: Our study identified a high rate of CPM among those with ATM, CHEK2, and PALB2 alterations, including VUS. Further studies are needed to clarify reasons for CPM among patients with moderate-risk alterations.