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.