Clinicopathologic features of invasive breast cancer (BC) diagnosed in carriers of germline PALB2, CHEK2 and ATM pathogenic variants.

Abstract

1549 Background: While germline pathogenic variants (PVs) in BRCA1/2 account for a large proportion of hereditary breast cancer (BC), PVs in PALB2, CHEK2 and ATM are increasingly detected. However, the phenotype and clinical features of invasive BC with these PVs have not been fully described. Methods: We identified patients with a PV or likely PV in PALB2, CHEK2 or ATM tested clinically at Stanford between 2014 - 2019 who provided informed consent to be included in a prospective cancer genetics registry. Data on baseline demographics, genetic testing history, and clinicopathologic features of diagnosed BC were collected. For patients with a subsequent diagnosis of metastatic BC, we calculated disease-free interval (DFI). Results: 130 patients met inclusion criteria for analysis: ATM (N=39), CHEK2 (N=58), PALB2 (N=33). Nearly all (98.5%) were women, with 2 male BC in ATM carriers. Non-Hispanic White ethnicity was most common in ATM (64.1%, 95% CI 48.4%-77.3%) and CHEK2 carriers (69.0%, 95% CI 56.1%-79.4%), but comprised only 39.4% (95% CI 24.7%-56.4%) in PALB2 carriers. Asian/Pacific Islander (24.2%, 95% CI 12.6%-41.3%) and Hispanic (30.3%, 95% CI 17.3%-47.5%) ethnicities were enriched among PALB2 mutation carriers. In total, 97.7% learned of their PV status only after a preceding diagnosis of BC and 43.1% were diagnosed with BC at age ≤ 45. Data regarding invasive BC subtypes, incidence of subsequent primary BC, and metastatic recurrence are listed below in the table. Additional data on stage, grade and sites of metastatic spread will be presented. Conclusions: We observed clinically important differences in the spectrum of BC subtypes among carriers of ATM, CHEK2 and PALB2 PVs, in addition to racial/ethnic differences with Asian/Pacific Islander and Hispanic ethnicity enriched among carriers of PALB2 PVs. [Table: see text]