Histopathologic and demographic features of non-small cell lung cancer in patients with <i>BRCA</i> pathogenic germline variants.

10573 Background: Patients with pathogenic germline variants (PGVs) in BRCA1 and BRCA2 ( BRCA1/2 ) have a known increased risk of breast, pancreatic, and prostate cancers. Limited data also suggest a potential increase in lung cancer risk. It is not known if the features of non-small cell lung cancer (NSCLC) in individuals with BRCA1/2 PGVs differ from those in PGV negative patients. Methods: Patients with BRCA1/2 PGVs were identified using a single-institution registry of PGV patients. Using electronic health records, NSCLC cases were identified via ICD codes. Demographic and histopathologic data were manually abstracted. A PGV negative cohort was derived from NSCLC patient cases detailed in the Penn Medicine Cancer Registry. Categorical variables were compared between the BRCA1/2 PGV and PGV negative groups using Pearson’s chi-squared test. Continuous variables were compared using the Wilcoxon rank-sum test. Results: 25 NSCLC patients with PGVs (10 BRCA1 and 15 BRCA2 ), and 623 PGV negative NSCLC patients were identified. Median age at diagnosis was similar (68, IQR=14 vs 67, IQR=13 years for BRCA1/2 PGV and PGV negative patients, respectively); sex (64% vs 51% female) and race (80% vs 74% White) were also similar between groups. Never smokers comprised a significantly larger proportion of the BRCA1/2 PGV cohort (44%) than the PGV negative cohort (16%; p&lt;0.01). Stage at diagnosis was similar between groups, with the majority diagnosed with stage I or II disease (56% in BRCA1/2 PGV vs 66% in PGV negative patients). Histologic findings were also similar, with the most common being adenocarcinoma and squamous cell (68% and 20% in BRCA1/2 PGV vs 71% and 19% in PGV negative patients, respectively). All 14 BRCA1/2 PGV patients with stage I-II disease received curative intent local therapy; there were 3 recurrences within 5 years. Among 11 BRCA1/2 PGV patients with advanced stage III-IV disease, 6 had actionable genetic alterations, most commonly in EGFR (3/11). PD-L1 status in these patients was evenly distributed, 3 &lt;1%, 5 1-49%, and 3 &gt;50% expression. Conclusions: The histopathologic and demographic features of NSCLC including age and stage at diagnosis and distribution of histology were largely similar for BRCA1/2 PGV patients and PGV negative patients. However, never smokers represented a significantly larger proportion of the BRCA1/2 PGV cohort. The presence of actionable genetic alterations and PD-L1 expression in BRCA1/2 PGV patients with NSCLC was comparable to those reported in the general NSCLC population. Features of NSCLC in patients with BRCA1/2 PGVs compared to PGV negative patient. BRCA1/2 PGV(N=25) PGV Negative(N=623) p -value Median age of onset, years, ± IQR 68±14 67±13 0.68 Female Sex 16 (64%) 319 (51%) 0.21 Never Smoker 11 (44%) 99 (16%) &lt;0.01 Stage I or II at diagnosis 14 (56%) 370/561 (66%) 0.20 Histology Adenocarcinoma 17 (68%) 445 (71%) 0.71 Squamous cell 5 (20%) 120 (19%) 0.92