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Molecular subtype discordance in bilateral synchronous breast cancer is a relatively uncommon entity that poses unique therapeutic challenges. Here we report the case of a 35-year-old woman who presented to our clinic with synchronous bilateral breast cancer (SBBC), with stage IIA triple-negative disease in the right breast and a stage IIB hormone-sensitive tumor in the left breast. She was treated with bilateral modified radical mastectomy and axillary node dissection followed by adjuvant chemotherapy, radiotherapy, and a five-year regimen with daily tamoxifen. To date, the patient remains asymptomatic and free of disease recurrence 78 months after initiating treatment. Little is known about SBBC with a discordant molecular subtype and reports about this entity are scarce. Future studies aimed at identifying the optimal management strategy for this disease are needed.

Background: The PALB2 gene is recognized as one of the most clinically relevant moderate to high penetrance breast cancer (BC) predisposition genes. Its product, PALB2, plays a crucial role in the homologous recombination pathway as a partner and localizer of BRCA2. Previous studies have reported significant frequencies of germline PALB2 and BRCA2 pathogenic variants (PVs) in Hispanic populations. However, no study has yet compared the baseline clinicopathological features of Mexican BC patients who carry PVs in these closely related genes. Methods: Medical records of BC patients from two centers located in Monterrey, Mexico who underwent a next-generation sequencing panel for BC predisposition genes (APC, ATM, BRCA1, BRCA2, BRIP1, CHEK2, CDH1, CDKN2A, MLH1, MSH2, MSH6, MUTYH, NF1, PALB2, PMS2, PTEN, RAD50, RAD51C, RAD51D, TP53) based on NCCN recommendations were reviewed. Patients with germline PVs in PALB2 or BRCA2 were considered eligible. Fisher’s exact and Mann Whitney U tests were employed to evaluate differences between groups based on mutation status. Results: Between 2014 and 2019, a total of 8 PALB2 (1.8%) and 24 BRCA2 (5.5%) pathogenic mutation carriers were identified from 437 BC cases. Baseline clinicopathological features are shown in Table 1. Overall, no statistically significant differences were observed between groups. The most common germline PVs were c.2167_2168delAT, p.Met723fs, frameshift mutation for PALB2 (57% of cases) and c.274C>T, p.Gln92Ter, nonsense mutation for BRCA2 (30% of cases). Of note, one male BC case occurred in a PALB2 mutation carrier, representing 13% (1/8) of BC cases in this carrier group and the only male BC case (out of three) associated with a germline PV. Conclusion: This is the first report detailing the clinicopathological features of Mexican BC patients with germline PALB2 PVs. According to our findings, BC tumors in PALB2 mutation carriers share similar baseline characteristics with those diagnosed in BRCA2 mutation carriers. Long-term follow-up is required in order to determine if prognosis is similar between groups and to further solidify the clinical relevance of germline PALB2 PVs in the Mexican population. Baseline clinicopathological features of PALB2 and BRCA2 mutation carriers with BCPALB2 mutation carriersBRCA2 mutation carriersMedian age at diagnosis (years)3938Median body mass index (kg/m2)2326Family history of BCYes5 (63%)19 (79%)No3 (38%)5 (21%)Clinical stageI2 (25%)2 (8%)II5 (63%)11 (46%)III08 (33%)IV1 (13%)3 (13%)Histological typeIDC6 (75%)22 (92%)Non-IDC2 (25%)2 (8%)Histological gradeG11 (13%)5 (21%)G24 (50%)10 (42%)G33 (38%)6 (25%)Missing03 (13%)Molecular subtypeHR+/HER2-6 (75%)11 (46%)HR+/HER2+04 (17%)HR-/HER2+00HR-/HER2-2 (25%)9 (38%)LateralityUnilateral8 (100%)21 (88%)Bilateral03 (13%) Citation Format: Alejandro Aranda-Gutierrez, Ana S Ferrigno, Juan Carlos A. García Marrufo, Mariana Moncada-Madrazo, Analy Gomez-Picos, Cynthia Villarreal-Garza, Dione Aguilar. Clinicopathological features of PALB2 and BRCA2 mutation carriers with breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-29.

Background: The implementation of genetic cancer risk assessment (GCRA) has resulted in an increased identification of adult males with breast cancer (BC) predisposing mutations. However, its effect on adherence to cancer prevention strategies and the psychological impact of receiving a positive genetic test result have not been sufficiently explored in men. The aim of this study is to determine the impact of GCRA on men with BC predisposing mutations. Methods: Men aged ≥18 years that underwent genetic testing between 2017 and 2019 in a center located in Monterrey, Mexico were invited to answer a telephone survey in which clinical information was collected. In addition, a section with an adapted Multidimensional Impact of Cancer Risk Assessment (MICRA) was incorporated. Total MICRA score was determined as the mean of items 1-21. Furthermore, seven sections were analyzed separately: distress (items 1-4 and 7-8), uncertainty (items 9-12, 14-17 and 20), positive experiences (items 5-6 and 18-19), understanding choices (item 13), testing regret (item 21), worry about children (items 22-23) and worry about cancer (items 24-25). Differences between categorical variables were explored using Mann Whitney U tests. Results: A total of 31 patients were eligible for this study, of which 29 consented to participate. Of these, 15 were mutation carriers (8 BRCA1, 3 BRCA2, 2 ATM, 1 CHEK2 and 1 PALB2) with a median age of 45 years (range 20-71). Only one of the carriers surveyed had a personal history of BC. The median time elapsed from disclosure of positive carrier status to survey application was 13 months. Remarkably, 3/15 ignored their test result despite previous GCRA, and only 4/15 were able to identify the specific mutated gene. Most had disclosed their mutation status to close relatives (67%). Regarding psychological impact, 2/15 thought that their genetic test result had a significant impact in their life and 1/15 claimed that undergoing genetic testing generated feelings of anxiety or depression. In addition, two out of three childless carriers reported that their mutation status made them seriously doubt whether to have biological children. Notably, only 47% were aware about the mode of transmission of their mutation. Concerning medical support, 87% felt that the support offered by the medical team was sufficient, but only 60% considered that they had enough information about the implications of their carrier status. With respect to prevention strategies, 67% claimed to be unaware about the general recommendations according to their mutational status and age. Furthermore, 87% did not use sunscreen, 80% had never visited a dermatologist, 73% could not correctly identify suspicious signs for skin cancer, 8/11 (72%) of eligible patients did not perform routine breast self-exams, and 10/11 (91%) had not visited a physician for a clinical breast exam. In addition, 0/6 (0%) of the eligible patients had had a colonoscopy and 5/6 (83%) eligible patients had not undergone screening for prostate cancer. Concerning the MICRA score, patients with BC predisposing mutations had a higher total mean score than non-carriers (21.7 vs. 14.3; p=0.01), particularly due to the positive experiences subscale (11.5 vs. 5.4; p=0.01). Conclusion: Low awareness and poor adherence to recommended prevention strategies were found in male mutation carriers despite a high impact of GCRA in this group. Hence, efforts to elucidate the specific barriers that limit adherence to these strategies in men are warranted. MICRA scores. Results are shown as mean (standard deviation).Mutation carriers (n=15)Non-carriers (n=14)p valueTotal score21.7 (8.5)14.3 (7.8)0.008Distress subscale2.1 (4.0)1.1 (1.9)0.617Uncertainty subscale6.0 (6.3)5.6 (7.1)0.603Positive experiences subscale11.5 (5.2)5.4 (7.2)0.013Understanding choices item2.0 (2.2)2.1 (2.1)0.841Testing regret item0.1 (0.3)0.0 (0.0)0.779Worry about children section2.5 (3.1)3.7 (3.3)0.569Worry about cancer section5.0 (0.0)5.0 (0.0)>0.99 Citation Format: Ana S Ferrigno, Alejandro Aranda-Gutierrez, Mariana Moncada-Madrazo, Arantza Montemayor-Solis, Julia S Arango-Vasquez, Juan CA Garcia-Marrufo, Lourdes Martinez-Ordaz, Cynthia Villarreal-Garza, Dione Aguilar. Impact of genetic cancer risk assessment on males with breast cancer predisposing mutations [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-23.