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: A substantial proportion of triple-negative breast cancer (TNBC) patients harbors a germline BRCA1/2 mutation. However, the impact of these mutations on recurrence-free survival (RFS) and overall survival (OS) rates remains controversial.Methods: Medical records of women diagnosed with BC between January 2013 and 2020 in two centers located in Monterrey, Mexico were reviewed. Only stage I-III TNBC patients who had available genetic test results and at least 12 months of followup were considered eligible. Fisher's exact tests were used to evaluate differences between groups based on mutation status. Furthermore, RFS and OS were calculated using the KaplaneMeier method, employing the log-rank test for group comparisons.Results: A total of 279 patients were diagnosed with TNBC, of which 162 (58%) had undergone genetic testing. Of these, 106 patients were considered eligible. Overall, 58 (55%) were negative for germline mutations and 48 (45%) had pathogenic BRCA mutations (36 BRCA1 [34%] and 12 BRCA2 [11%]). The median follow up was 31 months. The estimated 2.5-years RFS was 81.9% (confidence interval [CI] 95% 63.8-91.5%) for BRCA1 carriers, 71.4% (CI95% 33.8-90.1%) for BRCA2 carriers and 73.7% (CI95% 58.8-83.9%) for non-carriers (p>0.05). The estimated 2.5-years OS was 91.2% (CI95% 75.1-97.1%) for BRCA1-mutated, 73.3% (CI95% 24.3-93.4%) for BRCA2mutated and 77.1% (CI95% 62.3-86.7%) for non-mutated patients (p>0.05).Conclusions: There was a higher prevalence of BRCA2 mutation carriers in our TNBC cohort compared to what has been previously reported in the literature. BRCA1/2 carrier status was not found to be associated with statistically significant differences in RFS or OS at 2.5 years. However, there was a notable difference in OS at 2.5 years between BRCA1 carriers and non-BRCA1 carriers. Longer follow-up is required to determine if the observed survival advantage in BRCA1 carriers is maintained.Legal entity responsible for the study: The authors.

to 31 Oct 2015. Patients had a representative tumor specimen (formalin-fixed, paraffin-embedded archival) for testing of PDL1 expression. We collected the clinicopathological characteristics of the patients. The median follow-up time was 66.9 months. The 5-year DFS rate was 86.1% (95% CI 81.4%-90.8%) and the 5-years OS rate was 93.6% (95% CI 91.0%-97.6%). In the univariate analysis, we found that lymph nodes, Ki67 index and PDL1 expression were associated with DFS and OS; however, in the multivariate analysis, patients with PDL1 expression showed significantly more favorable prognosis in DFS (HR 2.875, 95%CI 1.216-6.796, p¼0.016) and improve the OS compared with the PDL1 negative group (HR 3.157, p¼0.088).Conclusions: PDL1 protein expression is a predictive biomarker of good prognostic factor for survival in triple-negative breast cancer patients.Legal entity responsible for the study: The authors.