Prospective Assessment For Pathogenic Germline Alterations (Pga) In Pancreas Cancer (Pac).

4102 Background: Cancer predisposition syndromes are identified in a subset of PAC. Identifying PGA has implications for therapy as well as for cancer predisposition in blood relatives. Germline testing (GT) in the US is currently performed in a small subset of PAC patients according to NCCN/other guidelines. At MSKCC, we have implemented an ‘opt in’ strategy to perform germline testing in all patients evaluated in PAC clinics at MSKCC. Methods: PAC pts consented prospectively for GT had samples analyzed for pathogenic or likely pathogenic variants using the MSK-IMPACT germline platform (NCT01775072). All pts first had somatic profiling of tumor samples for > 340 genes by MSK-IMPACT. Clinicopathological features, time to progression on platinum (TTPP) and overall survival (OS) were collated. Results: N = 305 PAC pts consented for GT between 9/2015-11/2016.164/305 (54%) were male, 70/305 (23%) were Ashkenazi Jewish. 242 pts (79%) had a family hx of cancer. 67/305 (22%) had a GA identified, 45/67 (67%) were stage III/IV at dx. Median age at PAC dx for all GA carriers was 60 years (y) (range 29-81) compared to 66 y (18-69) without GA. Median age at dx was 54 y (32-68) for BRCA1 and 61 y (37-77) for BRCA2 GA. 3/9 and 3/20 pts with BRCA1/2 GA had a PAC dx < 50 y. 2/63 pts (3%) with no family hx had a GA (CDKN2A, PMS2). N = 5/22 pts (23%) with a 1 st degree relative (DR) with PAC had a GA. N = 13/45 pts (29%) had a GA with either a 1 st or 2 nd DR with PAC. 19/84 pts (23%) with ≥2 1 st DR with cancer had a GA detected. For median OS and TTP on platinum therapy, see Table. Pts with BRCA1/2, ATM and those with coexisting GA tended to have a better median OS as well as longer TTP on platinum therapy (Table). Conclusions: GA’s are significantly under identified in PAC using current practices with a high, frequency (22%) observed in this relatively unselected cohort. BRCA mutations are the most frequent GA noted. There are significant implications of these observations for therapy and for blood relatives. [Table: see text]