Contralateral Risk-reducing Mastectomy Research Articles

Abstract PO5-19-02: I-PREPARE: International Prospective REgistry on Pre-pectorAl breast Reconstruction (EUBREAST 11R-NCT 05817175)

Abstract Background: Despite the progressive de-escalation of breast cancer (BC) surgery, mastectomy rates remain around 30-40%. Furthermore, up to 1/3 of BC patients undergo a contralateral risk-reducing mastectomy and around 40% of mutation carriers choose a bilateral intervention. To date, immediate breast reconstruction (IBR) with implants is the most commonly performed reconstructive procedure. After an initial experience with implants in subcutaneous positioning under the mastectomy flap in the seventies, this technique was abandoned due to a high rate of implant loss (28%), flap necrosis (13.5%) and capsular contracture (56%). For this reason, the positioning of the implant under the pectoralis major has become the standard of care. However, over time surgical techniques and implants have improved, resulting in decreasing implant loss, flap necrosis and capsular contracture rates. Moreover, biological/synthetic meshes have been used to cover the implant placed over the pectoralis major, thus avoiding to mobilize the muscle with some benefits in terms of reduced complications (no animation deformity, no chronic pain, no loss of muscular function), patients’ wellbeing, postoperative pain and recovery. Additionally, recent literature reported encouraging results with polyurethane breast implants in pre-pectoral positioning without any kind of implant coverage. Although these procedures are considered safe they were not evaluated in prospective randomized trials. In 2019 a joint consensus on pre-pectoral breast reconstruction (PBR) clearly recommended to properly audit the results in terms of surgical complications and patient-reported outcomes. Based on these premises the EUBREAST (European Breast Cancer Research Association of Surgical Trialists, www.eubreast.org) study group decided to launch a prospective international cohort study aimed at comparatively evaluating data on different surgical techniques of PBR with or without PMRT. Therefore, we will prospectively evaluate the utilization of PBR, including surgical, oncological, aesthetic and patients’ satisfaction and quality of life outcomes related to each type of surgical technique and the interaction with post-mastectomy radiation therapy (PMRT). Eligibility criteria: - Female patients age≥18 years - Signed informed consent - Patients undergoing mono/bilateral therapeutic mastectomy and immediate PBR Exclusion criteria - Patients not suitable for surgical treatment - Patients undergoing subpectoral reconstruction, reconstruction with tissue expander or autologous IBR Specific aims: The primary endpoint is implant-loss at 3 months defined as the unplanned removal or loss of the implant, as a result of infection or any other complication Secondary endpoints are infection, re-admission and re-operation rates, quality of life evaluated through BREASTQ Breast Reconstruction Module and EQ-5D-5L questionnaires on an App for patients before and after breast reconstruction at 6, 12, 24 months, early onset complication at 3 months, late-onset complications at 6, 12, 24 months, further surgery at 24 months, time to adjuvant therapy. Tertiary endpoints are further surgery, loco-regional recurrence, disease free survival, breast cancer specific survival, distant-disease free survival, overall survival, development of seroma/breast implant-associated anaplastic cell lymphoma. Statistics: We will use a single-arm design to assess the surgical safety of PBR through implant loss rate at 3 months which is expected to be ≤9% based on previous literature; 12% or greater will be regarded as unacceptably high. The assessment will be based on 1,112 patients. For this sample size calculation, power was set to 90%, and the two-sided alpha was set to 0.05. Allowing for a 10% loss to follow-up at 3 months, we aim at recruiting 1,236 patients. Accrual has not started yet. Funding: EUBREAST ETS Italy Contact: Oreste Davide Gentilini: gentilini@eubreast.org Citation Format: Rosa Di Micco, Maggie Banys-Paluchowski, Maria-Joao Cardoso, Jana de Boniface, Bahadir M. Gulluoglu, Orit Kaidar-Person, Thorsten Kühn, Maurizio Bruno Nava, Philip Poortmans, Shelley Potter, Nicole Rotmensz, Tanja Spanic, Marc Thill, Luzia Travado, Walter Weber, Oreste Davide Gentilini. I-PREPARE: International Prospective REgistry on Pre-pectorAl breast Reconstruction (EUBREAST 11R-NCT 05817175) [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 PO5-19-02.

Simultaneous bilateral mastectomy and RRSO for BRCA2-positive non-invasive breast cancer in Japan: a case report and analysis of initial experience.

In Japan, genetic testing, surveillance, and risk-reducing surgery for hereditary breast and ovarian cancer (HBOC) syndrome have been covered by the Japanese national insurance system since April 2020. On the other hand, the current situation is that medical care, including surveillance of undiagnosed (cancer-free) patients, is self-funded even for individuals with HBOC. We report a case in which breast cancer was diagnosed at an early stage during surveillance for cancer-free HBOC at the patient's own expense, and risk-reducing surgery was performed at the same time as treatment for breast cancer. The patient was a 63-year-old woman. Her sister had a history of breast cancer in her 30s and was found to be a BRCA2 pathogenic variant carrier by genetic testing. The patient therefore presented to the genetic department of our hospital and underwent genetic testing (out-of-pocket). A pathogenic variant was found at the same site. During annual breast and ovarian surveillance at the patient's own expense, a physician with sufficient expertise in contrast-enhanced breast magnetic resonance imaging (MRI) noticed a change in the contrast enhancement pattern on breast MRI and performed needle biopsy, revealing ductal carcinoma in situ. At the request of the patient, she underwent concurrent contralateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy in addition to breast cancer treatment. We encountered a case in which cancer treatment and risk-reducing surgery were performed at the same time for a pathogenic variant carrier who was very anxious about developing cancer. Surveillance of cancer-free BRCA1/2 mutation carriers and expansion of insurance coverage for surgery are important future issues.

Surgical Decision Making in Genetically High-Risk Women: Quantifying Postoperative Complications and Long-Term Risks of Supplemental Surgery After Risk-Reducing Mastectomy.

Risk-reducing mastectomy (RRM) helps prevent breast cancer in high-risk women but also carries a risk of unanticipated supplemental surgeries. We sought to determine the likelihood of supplemental surgeries following RRM. We performed a retrospective cohort study of female patients with a confirmed germline pathogenic variant (GPV) in a breast cancer susceptibility gene (BRCA1/2, PALB2 and others) who underwent bilateral or contralateral RRM at our institution between 2006 and 2022. Supplemental surgeries were defined as any operation requiring general or local anesthesia performed outside of the initially planned procedure(s). The Kaplan-Meier method was used to estimate the 5-years cumulative incidence of supplemental surgery. Of 560 GPV carriers, RRMs were performed in 258 (46.1%) women. The median age of the cohort was 44 years (interquartile range 37-52 years), with 33 (12.8%) patients undergoing RRM without reconstruction and 225 (87.2%) undergoing RRM with reconstruction. Following surgery, 34 patients (13.2%) developed early (< 30 days) postoperative complications, including infection, hematoma, seroma, loss of the nipple areola complex, flap necrosis, implant exposure and/or prosthesis removal. At a median follow-up of 3.8 years, 94 (36.4%) GPV carriers underwent at least one reoperation. Participants who experienced an early postoperative complication had the highest rate of reoperation (85.3% vs. 29.0%; p < 0.001) and a significantly higher likelihood of multiple additional surgical interventions (41.2% vs. 10.7%; p < 0.001). The 5-years rate of supplemental surgery was 39.2% [95% confidence interval (CI) 32.7-46.5] in the overall cohort and 31.5% (95% CI 24.9-39.3) in patients without an early postoperative complication. Unanticipated supplemental surgeries occur in 40% of GPV carriers following RRM andin nearly one-third of patients without early postoperative complications.

Impact of risk-reducing mastectomy on quality of life of women with Li-Fraumeni syndrome.

10623 Background: Risk-reducing mastectomy (RRM) is a common strategy for managing breast cancer (BC) risk in women with Li-Fraumeni syndrome (LFS). Data on uptake and health-related quality of life (HRQoL) in LFS are limited and often extrapolated from BRCA scenario, despite the lack of evidence on survival benefits in LFS. This study evaluated RRM uptake and its impact on HRQoL in women with LFS. Methods: TP53 PV female carriers from a Brazilian LFS cohort from January 2012 to December 2022 were eligible. After informed consent, 90 women reported oncological status, uptake of RRM, and completed BREAST-Q questionnaire. Scores were compared among different BC risk management strategies and minimal important difference (MID) of ≥ 4 was described. Multivariable analyses were performed to identify surgical factors related to HRQoL outcomes. Results: 71.7% (n=33) of women diagnosed with unilateral BC (n=46) underwent contralateral risk-reducing mastectomy (CRRM) at a median age of 39 years. Among unaffected BC women (n=44), 36.3% underwent bilateral risk-reducing mastectomy (BRRM) at a median age of 36 years. CRRM was associated with lower scores for psychosocial (64[±19] vs 93[±21], p=.05) and physical well-being (72[±16] vs 92[±18], p=.001). BRRM women had lower physical well-being scores (72[±19] vs 92[±13], p=.003). MID associated with worst HRQoL outcomes were seen in all four domains on CRRM women and on satisfaction with breasts and physical well-being of BRRM patients (table). Nipple-sparing mastectomy (NSM) presented better psychosocial (74[±20] vs 52[±19], p=.04) and sexual well-being (60[±20] vs 46[±20], p=.05) when compared to skin-sparing mastectomy (SSM) on CRRM patients and with higher sexual well-being (60[±20] vs 46[±20], p=.05) on BRRM patients. Women with BRRM &gt; 2 years had better physical well-being (83[±14] vs 56 [±12], p&lt;.001). There were no significant differences in scores of women with age £35 years at the time of BRRM, although MID ≥ 4 was observed on psychosocial and sexual well-being and satisfaction with breasts: -23.0, -14.4, and -20.0, respectively. Conclusions: We observed high rates of RRM in LFS women and those were associated with worse outcomes on breast HRQoL in comparison to surveillance. The potential benefits and harms of RRM should be carefully discussed with patients before performing it, especially in LFS women where the survival benefits of these interventions remain uncertain. [Table: see text]

Prophylactic Risk-Reducing Mastectomy (PRRM): A Set Practice or Catch-22 Situation in LMIC. A Single-Centre Prospective Cohort Study.

Background Pakistan's hereditary breast cancer has a higher-than-average prevalence. Our acceptability of prophylactic risk-reducing mastectomy (PRRM) still needs to be determined, and genetic testing still needs to be offered to all eligible. The aim is to determine the number of women presenting to our centre who availed of PRRM after positive genetic tests and the main reasons restraining them from considering PRRM.Materials and methods This study is a single-centre, prospective cohort. We collected data from 2017 to 2022 on BRCA1/2 and other (P/LP) gene-positive patients. Continuous variables are presented as means (±SD) and categorical variables in percentages, with a significant P-value of ≤ 0.05.Results Out of 477 tested individuals, only 95(20.12%) had a positive result. BRCA1/2 was positive in 70 cases, while P/LP variants were in 24 cases. Only 32.6% of eligible families underwent genetic testing, with 54.8% positivity. Altogether, 92.6% of patients had BRCA1/2-related cancers. Only 25/95(26.3%) individuals availed of PRRM, the majority had contralateral risk-reducing mastectomy 68% with a 20% reconstruction rate. The main reasons to decline PRRM were false belief of not having any disease 57.44%, followed by family/spouse pressure 51%, body appearance/societal perception, fear of complications/quality of life and financial constraints.Conclusion Genetic testing and its implications are still a grey area for LMICs, primarily due to the scarcity of centres offering genetic testing to eligible populations, followed by prevalent perceptions about prophylactic surgeries among the masses. Addressing relevant issues in LMICs is the need of time.

Abstract PD14-09: PD14-09 The effect of timing of TP53 genetic testing on treatment and outcomes among women with Li-Fraumeni syndrome and breast cancer

Abstract Background: Li-Fraumeni syndrome (LFS) is a pan-cancer predisposition syndrome caused by pathogenic germline TP53 variants. Breast cancer (BC) is the most prevalent tumor in women with LFS. The risk of secondary malignancies, including multiple primary BCs, other LFS-related cancers, radiation-induced sarcomas, and local recurrences are important clinical concerns in the LFS setting. The diagnosis of LFS may influence treatment decisions and outcomes. Methods: In this international multicenter study, we analyzed women with pathogenic or likely pathogenic germline TP53 variants and BC (DCIS or invasive breast carcinoma) diagnosed 2002-2022 from three retrospective LFS cohorts (Dana Farber Cancer Institute, USA; Institut Gustave Roussy, France; Hospital Sírio-Libanês, Brazil). We excluded carriers of TP53 unconfirmed possibly mosaic variants, carriers of a 2nd pathogenic variant in another BC susceptibility gene, and those with missing data related to timing of genetic testing (TGT) or date of 1st BC diagnosis (dx). The overall cohort was divided in two groups: genetic testing before or at 1st BC dx (group A) and those with testing ≥1 year after 1st BC dx (group B). In cases with synchronous bilateral BC, we included the tumor of higher risk of recurrence (invasive, higher stage, more aggressive tumor biology) and excluded the other. The chi-square test was used to measure the association between TGT and other categorical variables. Results: 209 patients (pts) met criteria for this analysis. The median age of 1st BC dx was 35 years (IQR, 31-42). BC was the 1st cancer dx in 87.5% of the pts. Among 1st breast tumors, 38 were DCIS, 147 were early-stage BC (61 I, 49 II, 37 III) and 7 stage IV (17 missing). There were no differences between groups A and B regarding staging at dx. Missense TP53 variants were the most common type of germline mutation (n=154, 73.6%), with 60.4% (n=93) in the DNA-binding domain and 38.9% (n=60) in the tetramerization domain. Median follow-up from 1st BC dx was 6 years (IQR, 3-10). 53.1% of pts (n=111) underwent TP53 germline testing only after 1st BC dx. Family history of BC &amp;lt; 50 and non-BC malignancy prior to or synchronous with 1st BC dx were not associated with TGT (p=0.3 and p=0.2, respectively). 35.4% of pts developed a second primary BC (25 ipsilateral; 49 contralateral). Among pts without synchronous bilateral BC or metastatic BC at dx, 97 pts underwent contralateral risk reducing mastectomy (CRRM), 56.7% (55/97) as part of treatment surgery for the 1st BC. CRRM uptake was associated with TGT (A 70.3% vs B 41.6%, p=0.001). Of 194 pts with detailed data on surgical treatment (1st BC), 146 underwent mastectomies and 48 breast conserving surgery (BCS). Group A had more mastectomies (79.5% vs 61.2%, p=0.001) and less radiation therapy (10.2% vs 45.9%, p&amp;lt; 0.001). Among the irradiated pts, 9.8% (n=5) developed sarcomas in the irradiated field. Thirty-eight pts had BC recurrence: 21 loco-regional (A 6 vs B 15, p&amp;lt; 0.05), mostly in-breast, and 17 distant relapses. There was a significant statistical association between TGT and type of BC surgery (p=0.001), radiation-therapy (p&amp;lt; 0.001), CRRM uptake (p=0.001) and local relapses (p&amp;lt; 0.05). Conclusion: This analysis of BC in our sizable cohort of LFS patients with treatment data confirms that, timing of genetic testing affects some treatment options and outcomes, including surgical procedures and use or avoidance of radiation. These decisions appear to influence the risk of local recurrence or additional primary BC and radiation-induced sarcoma. Recognition of germline TP53 variants in breast cancer patients as part of genetic testing at diagnosis appears to have implications for treatment options and outcomes. Citation Format: Renata Sandoval, Michele Bottosso, Natalia Polidorio, Brittany Bychkovsky, Benjamin Verret, Alessandra Gennari, Sophie Hyman, Maria Isabel Achatz, Olivier Caron, Fabrice Andre, Judy Garber. PD14-09 The effect of timing of TP53 genetic testing on treatment and outcomes among women with Li-Fraumeni syndrome and breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD14-09.

Effectiveness of Prophylactic Mastectomy

Introduction: The growing incidence and recurrence rate of breast cancer has influenced multiple strategies such as surgical interventions that serve as preventive measures for women at high risk. Prophylactic mastectomy seems to be the most effective tool in the primary prevention of breast cancer, but opinions are not uniform, especially among specialists. The goal of this presentation is to examine the effect of risk-reducing mastectomy, including breast cancer incidence, breast cancer mortality, disease-free survival, physical morbidity, and psychosocial outcomes in cohort of patients who underwent prophylactic mastectomy. Materials and Methods: We retrospectively reviewed the outcomes of 20 years of experience with prophylactic mastectomies performed at the department from 1999 to 2019. In this study were included patients who underwent bilateral prophylactic mastectomy with no breast cancer, and patients with breast cancer, if they underwent contralateral risk-reducing mastectomy, however, only the prophylactic side was considered in the analysis. Patients with bilateral breast cancer were excluded. Results: A total of 749 risk-reducing prophylactic mastectomy in 545 patients were performed at our department from 1999 to 2019. Bilateral prophylactic mastectomies were performed in 204 patients (37,4%), and 341 (62,6%) underwent a unilateral risk-reducing mastectomy secondary to cancer in the contralateral breast. Overall, 243 patients with BRCA1 mutations and 113 with BRCA2 mutations were included. Conclusion: Prophylactic mastectomy is highly preventive against breast cancer. Although further clinical studies are needed to determine the effectiveness of prophylactic mastectomies in individual indications. With the effectiveness of prophylactic mastectomy should also be taken into consideration the quality of life after the immediate breast reconstruction, and the associated complications.

Risk-reducing surgery in PALB2 mutations carriers with breast cancer: a case series and literature review.

Inherited germline mutations in PALB2 are known to predispose patients to a higher risk of breast, ovarian and pancreatic cancer with an estimated risk of developing breast cancer in over half of all affected women by age 80 years. Current guidelines for screening patients with PALB2 mutations include annual mammograms beginning at age 30 years and consideration of breast magnetic resonance imaging (MRI) and tomosynthesis. Existing evidence regarding risk-reducing surgery with mastectomy is insufficient to make a definitive recommendation to patients. In this case series, we describe the presentation and management of 5 patients with unilateral breast cancer and PALB2 mutations. To our knowledge, this is the first reported case series discussing the role of contralateral risk-reducing mastectomy (CRRM) in breast cancer patients with PALB2 mutations. The aim of our study was to evaluate the challenges in managing breast cancer risk in patients with PALB2 pathogenic variants with illustration through real-world clinical cases and a review of the literature. In this retrospective observational study, we present 5 patients with PALB2 mutations between the ages of 29 and 61 years who were diagnosed with breast cancer and underwent surgical management of their breast cancer at our institution between November 2020 and March 2022. Through their clinical courses and a literature review, we discuss the role of CRRM in breast cancer patients with PALB2 gene mutations. Out of the 5 patients, 3 patients underwent CRRM and 2 patients chose unilateral surgery for their breast cancer and active surveillance for the contralateral breast. Of the 3 patients who underwent CRRM, 1 patient experienced a surgical complication from reconstruction on the prophylactic side. None of the patients developed any recurrences with an average length of follow up of 15.4 months. Based on our experience and the currently available literature, CRRM in patients with a PALB2 mutation should be performed on a case-by-case basis through a shared decision-making process taking into consideration overall risk, family history, patient preference and quality of life.

Points to Consider Regarding De-Escalation Surgery in High-Risk Breast Cancer.

For women affected by breast cancer who carry germline BRCA1/2 pathogenic variants, the classic standard treatment consists of therapeutic unilateral mastectomy and risk-reducing contralateral mastectomy. However, data from recent literature demonstrate that for women treated with breast-conserving surgery who receive adequate adjuvant treatments, the increased risk of locoregional recurrences and a breast cancer-related prognosis is not significant. This review describes the clinical factors that could help clinicians decide either against or in favor of a more aggressive type of breast cancer surgery.

266 Breast Cancer in Women Under 30: A Multidisciplinary Approach in a Unique Cohort

Abstract Aim Breast cancer in younger women is relatively rare, tends to be more aggressive and is associated with unique challenges. We sought to examine our practice in managing cancer in patients under 30. Method A retrospective case-note review was performed on patients under 30 years of age diagnosed with invasive breast through our pathology database since 2007. Clinical and pathological data was collected on patients’ cancers, management and follow up as well family history, genetic testing, and fertility management. Results Forty-five patients were identified. Median age was 28 years (range 20 to 30). Mean tumour size was 30mm (range 4–65mm). Seventeen (38%) of cancers were ER negative, 16 (36%) were HER2 positive. Twenty-three patients (51%) had positive lymph node metastases. SIx patients (13%) had a strong family history and 9 (20%) were BRCA 1 or 2 gene positive. Seven patients (15%) underwent contra-lateral risk-reducing mastectomy. Twenty-5 patients (55%) had no children at diagnosis. Fertility management was discussed with &amp;gt;90% of patients and 12 patients (26%) underwent ovum or embryo preservation. Over a median follow up of 40.5 months (range 4.5 to 128 months), 8 patients (18%) developed local or distant recurrence and 6 patients (13%) died (due to metastasis). Conclusion In our experience, breast cancer patients under 30 had more aggressive cancers with a relatively high rate of axillary metastases at presentation. Young patients with breast cancer face unique management challenges such as fertility, genetic testing and survivorship issues that are best addressed in a multidisciplinary setting.

Timely cancer genetic counseling and testing for young women with breast cancer: impact on surgical decision-making for contralateral risk-reducing mastectomy.

Genetic testing (GT) can identify individuals with pathogenic/likely pathogenic variants (PV/LPVs) in breast cancer (BC) predisposition genes, who may consider contralateral risk-reducing mastectomy (CRRM). We report on CRRM rates in young women newly diagnosed with BC who received GT through a multidisciplinary clinic. Clinical data were reviewed for patients seen between November 2014 and June 2019. Patients with non-metastatic, unilateral BC diagnosed at age ≤ 45 and completed GT prior to surgery were included. Associations between surgical intervention and age, BC stage, family history, and GT results were evaluated. Of the 194 patients, 30 (15.5%) had a PV/LPV in a BC predisposition gene (ATM, BRCA1, BRCA2, CHEK2, NBN, NF1), with 66.7% in BRCA1 or BRCA2. Of 164 (84.5%) uninformative results, 132 (68%) were negative and 32 (16.5%) were variants of uncertain significance (VUS). Overall, 67 (34.5%) had CRRM, including 25/30 (83.3%) PV/LPV carriers and 42/164 (25.6%) non-carriers. A positive test result (p < 0.01) and significant family history were associated with CRRM (p = 0.02). For the 164 with uninformative results, multivariate analysis showed that CRRM was not associated with age (p = 0.23), a VUS, (p = 0.08), family history (p = 0.10), or BC stage (p = 0.11). In this cohort of young women with BC, the identification of a PV/LPV in a BC predisposition gene and a significant family history were associated with the decision to pursue CRRM. Thus, incorporation of genetic services in the initial evaluation of young patients with a new BC could contribute to the surgical decision-making process.

A case of hereditary breast and ovarian cancer syndrome who underwent simultaneous contralateral risk-reducing mastectomy in the diagnosis of right breast cancer following primary peritoneal cancer

A case of hereditary breast and ovarian cancer syndrome who underwent simultaneous contralateral risk-reducing mastectomy in the diagnosis of right breast cancer following primary peritoneal cancer

Uptake and timing of bilateral and contralateral risk-reducing mastectomy in women with Li-Fraumeni syndrome.

Women with Li-Fraumeni Syndrome (LFS) often consider risk-reducing mastectomy (RRM) due to extremely high risk of breast cancer at early ages. Data on uptake of RRM in LFS are scarce, and are inferred from experience in women with pathogenic variants (PVs) in BRCA1/2, despite differences in cancer risks. This study evaluated RRM uptake in a cohort of women with LFS. Women (n = 205) with LFS enrolled in NCI's LFS study reported lifetime cancer diagnoses and mastectomies and completed questionnaires regarding reproductive history, cancer worry and risk perceptions. A subset of women participating in an annual cancer screening study received counseling regarding RRM. 65% (n = 71) ofwomen diagnosed with presumed unilateral breast cancer (n = 109) underwent contralateral RRM over their lifetime. Nearly half (49%, n = 25) of the women who did not complete contralateral RRM within one year of their breast cancer diagnosis (n = 51) developed contralateral breast cancer (median interval = 6years). Only 18.5% (n = 15) ofwomen without breast cancer history (n = 81) underwent bilateral RRM. Median age at bilateral RRM of 39years was sub-optimal for breast cancer risk reduction. Contralateral RRM was associated with early genetic diagnosis, participation in the screening study, and fewer prior cancers. Bilateral RRM uptake was associated with having had children, having breastfed, and high cancer worry. Uptake of contralateral RRM is high in women with LFS. The frequency of contralateral breast cancer necessitates active discussion of benefits of contralateral RRM and counseling regarding bilateral RRM should be tailored to the early age at risk of breast cancer onset in LFS. There is a need for research into the survival and long-term benefits of RRM in LFS.

Surgical management of BRCA pathogenic variant carriers with breast cancer: a recent literature review and current state of the art.

Surgical management of breast cancer patients carrying pathogenic variants (PV) on breast cancer genes (BRCA) 1 and 2 has changed throughout the last decade due to growing availability of genetic testing, and has shifted towards the diffusion of bilateral mastectomy. Today's scenario however is in further evolution because of emerging data that suggest a personalized modulation of treatment. In this work we aimed to gather recent evidence supporting a prophylactic or conservative surgical approach in order to define the state of the art in today's treatment of BRCA carriers with breast cancer. We reviewed the literature to identify studies providing evidence on surgical treatment in breast cancer patients with BRCA 1 and 2 PVs. We included articles comparing outcomes between patients undergoing breast conserving surgery (BCS) and mastectomy, and articles investigating contralateral risk-reducing mastectomy (CRRM), with a particular focus on recent literature. International guidelines were also reviewed. Optimal surgical management of BRCA PV carriers with breast cancer remains controversial. While the introduction of routine genetic testing has initially led surgeons to favor more radical treatments, recent literature provides evidence that a conservative approach is safe and feasible in selected cases. Guidelines are heterogeneous and provide guidance without constraining the surgeon. Patients should undergo adequate genetic and surgical counseling in order to receive the best tailored surgical treatment. Because guidelines vary in different countries and provide no definite protocol, they highlight the importance of accurate surgical planning. Clinical, familial and psychosocial factors should be taken into account when approaching a BRCA PV carrier with breast cancer, in order to guarantee the best evidence-based patient care in an era of personalized treatment.

Preoperative diagnosis of BRCA1/2 mutation impacts decision-making for risk-reducing mastectomy in breast cancer patients

Decision to undergo risk-reducing mastectomy (RRM) needs to consider several factors, including patient’s preference, surgeon’s preference, family history, and genetic predisposition. The aim of this study was to examine whether preoperative diagnosis of BRCA1/2 mutation status could influence surgical decision-making in newly diagnosed breast cancer patients. We retrospectively reviewed ipsilateral breast cancer patients with BRCA1/2 mutation who underwent primary surgery between January 2008 and November 2019 at a single institution in Korea. Of 344 eligible patients, 140 (40.7%) patients were aware of their mutation status ‘prior to surgery’, while 204 (59.3%) did not. Contralateral RRM rate was significantly higher in the group with BRCA1/2 mutation status identified ‘prior to surgery’ compared to the group with mutation status identified ‘after surgery’ [45.0% (63/140) vs. 2.0% (4/204)] (p < 0.001). Reduced turnaround time of BRCA1/2 testing (p < 0.001) and the use of neoadjuvant chemotherapy (p < 0.001) were associated with BRCA1/2 mutation status identified prior to surgery. Although not statistically significant, higher incidence of developing contralateral breast cancer for BRCA1/2 mutation carriers who underwent ipsilateral surgery-only compared to those who underwent contralateral RRM was observed [12.1% (95% CI: 7.7–17.7%)] (p = 0.1618). Preoperative diagnosis of BRCA1/2 mutation could impact surgical decision-making for breast cancer patients to undergo risk-reducing surgery at the time of initial surgery.

The Angelina Jolie effect: Contralateral risk-reducing mastectomy trends in patients at increased risk of breast cancer

Contralateral risk-reducing mastectomy (CRRM) rates have tripled over the last 2 decades. Reasons for this are multi-factorial, with those harbouring a pathogenic variant in the BRCA1/2 gene having the greatest survival benefit. On May 14th, 2013, Angelina Jolie shared the news of her bilateral risk-reducing mastectomy (BRRM), on the basis of her BRCA1 pathogenic variant status. We evaluated the impact of this news on rates of CRRM in women with increased risk for developing breast cancer after being diagnosed with unilateral breast cancer. The prospective cohort study included all women with at least a moderate lifetime risk of developing breast cancer who attended our family history clinic (1987–2019) and were subsequently diagnosed with unilateral breast cancer. Rates of CRRM were then compared between patients diagnosed with breast cancer before and after Angelina Jolie’s announcement (pre- vs. post-AJ). Of 386 breast cancer patients, with a mean age at diagnosis of 48 ± 8 years, 268 (69.4%) were diagnosed in the pre-AJ period, and 118 (30.6%) in the post-AJ period. Of these, 123 (31.9%) underwent CRRM, a median 42 (interquartile range: 11–54) days after the index cancer surgery. Rates of CRRM doubled following AJ’s news, from 23.9% pre-AJ to 50.0% post AJ (p < 0.001). Rates of CRRM were found to decrease with increasing age at breast cancer (p < 0.001) and tumour TNM stage (p = 0.040), and to increase with the estimated lifetime risk of breast cancer (p < 0.001) and tumour grade (p = 0.015) on univariable analysis. After adjusting for these factors, the step-change increase in CRRM rates post-AJ remained significant (odds ratio: 9.61, p < 0.001). The AJ effect appears to have been associated with higher rates of CRRM amongst breast cancer patients with increased cancer risk. CRRM rates were highest amongst younger women and those with the highest lifetime risk profile. Clinicians need to be aware of how media news can impact on the delivery of cancer related services. Communicating objective assessment of risk is important when counselling women on the merits of risk-reducing surgery.

Survey on Physicians’ Knowledge and Training Needs in Genetic Counseling in Germany

Background: In recent years, germline testing of women with a risk of developing breast and ovarian cancer has increased rapidly. This is due to lower costs for new high-throughput sequencing technologies and the manifold preventive and therapeutic options for germline mutation carriers. The growing demand for genetic counseling meets a shortfall of counselors and illustrates the need to involve the treating clinicians in the genetic testing process. This survey was undertaken to assess their state of knowledge and training needs in the field of genetic counseling and testing. Methods: A cross-sectional survey within the European Bridges Study (Breast Cancer Risk after Diagnostic Gene Sequencing) was conducted among physician members (n = 111) of the German Cancer Society who were primarily gynecologists. It was designed to examine their experience in genetic counseling and testing. Results: Overall, the study revealed a need for training in risk communication and clinical recommendations for persons at risk. One-third of respondents communicated only relative disease risks (31.5%) instead of absolute disease risks in manageable time spans. Moreover, almost one-third of the respondents (31.2%) communicated bilateral and contralateral risk-reducing mastectomy as an option for healthy women and unilateral-diseased breast cancer patients without mutations in high-risk genes (e.g. BRCA1 or BRCA2). Most respondents expressed training needs in the field of risk assessment models, the clinical interpretation of genetic test results, and the decision-making process. Conclusion: The survey demonstrates a gap of genetic and risk literacy in a relevant proportion of physicians and the need for appropriate training concepts.

A Retrospective Analysis of the Relationship Between the Result of BRCA1/2 Genetic Testing and Surgical Method Selection in Japan

BackgroundWe studied the extent of BRCA1/2 genetic testing to help select the surgical approach for patients with breast cancer in Japan remains unclear. Patients and MethodsThe study subjects were female patients with primary unilateral invasive breast cancer considered as candidates for breast-conserving surgery who underwent preoperative BRCA1/2 genetic testing. A retrospective analysis was performed on the results of BRCA1/2 genetic testing and surgical method selection using national registration data from the Japanese Hereditary Breast and Ovarian Cancer Syndrome Consortium. ResultsOur study included 318 female patients. Among these patients, 23.7% of patients with BRCA1/2 mutations and 61.8% of patients without these variants underwent breast-conserving surgery (P < .01). Among the patients with BRCA1/2 mutations, those who chose breast-conserving surgery tended not to undergo risk-reducing salpingo-oophorectomy (P < .05). Among the patients with BRCA1/2 mutations who underwent mastectomy for the affected side, 31.8% received contralateral risk-reducing mastectomy. Patients diagnosed with breast cancer under the age of 50 years were more likely to have contralateral risk-reducing mastectomy than patients over the age 50 years (P < .05). ConclusionsPatients with BRCA1/2 mutations tend to choose mastectomy. However, it is speculated that the final surgical method selection is made in consideration of not only the test results but also with careful consideration of the patient, taking into account other factors including individual values for risk-reducing surgeries and the age of breast cancer onset.

Contralateral Risk-Reducing Mastectomy in Breast Cancer Patients Who Undergo Multigene Panel Testing.

An increasing number of breast cancer patients are undergoing expanded genetic testing and are being identified as germline mutation carriers. We sought to determine rates of contralateral risk-reducing mastectomy (CRRM) in patients with various germline mutations. All women ≥ 18years of age with unilateral breast cancer who underwent multigene panel testing between January 1, 2014 and August 1, 2019 at our academic institution were identified. Demographic, tumor, and treatment variables were identified from the medical record. Multivariable analyses were performed to compare factors associated with performance of CRRM. We identified 1613 patients, of whom 28.1% had a pathogenic variant and 40.1% had variants of uncertain significance (VUS). Overall, 420 patients (26.0%) underwent a CRRM. On multivariable analysis, factors associated with CRRM included age < 50years (OR 3.8, 95% CI 3.0, 5.0), race (OR 0.5, 95% CI 0.3, 0.7 and OR 0.4, 95% CI 0.2, 0.7 for Black and Asian women, respectively, versus White women), and the presence of any germline mutation or VUS (OR 13.2, 95% CI 8.7, 20.2 for BRCA1/2; OR 3.9, 95% CI 2.7, 5.8 for non-BRCA germline mutation; and OR 1.8, 95% CI 1.3, 2.6 for VUS). In breast cancer patients who undergo multigene panel testing, a sizeable number of women with pathogenic non-BRCA germline findings are opting for CRRM. Given that the risk of contralateral breast cancer in women with most pathogenic mutations other than BRCA1/2 remains poorly characterized, these data have implications for risk counseling and for ascertaining the true risks of contralateral breast cancer in this population.

ASO Author Reflections: Performance of Contralateral Risk-Reducing Mastectomy in Multigene Panel-Tested Patients is High in All Types of Germline Mutation Carriers.

ASO Author Reflections: Performance of Contralateral Risk-Reducing Mastectomy in Multigene Panel-Tested Patients is High in All Types of Germline Mutation Carriers.