Homologous recombination deficiency (HRD) by BROCA-HR and survival outcomes after surgery for patients (pts) with pancreatic adenocarcinoma (PC): A single institution experience.

Authors

null

Amy E. Chang

University of Michigan, Ann Arbor, MI

Amy E. Chang , David Bing Zhen , Marc Radke , Kelsey K. Baker , Andrew L. Coveler , Kit Man Wong , Venu Gopal Pillarisetty , Mary Weber Redman , Elizabeth Swisher , E. Gabriela Chiorean

Organizations

University of Michigan, Ann Arbor, MI, University of Washington School of Medicine, Seattle, WA, Fred Hutchinson Cancer Research Center, Seattle, WA, Seattle Cancer Care Alliance/University of Washington, Seattle, WA, University of Colorado, Denver, CO, University of Washington, Seattle, WA, SWOG Statistical Center; Fred Hutchinson Cancer Research Center, Seattle, WA, University of Washington/Seattle Cancer Care Alliance, Seattle, WA, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA

Research Funding

U.S. National Institutes of Health
U.S. National Institutes of Health

Background: 5-7% of PC pts exhibit deleterious germline mutations (MUT) in HR tumor suppressor genes BRCA1 and BRCA2. BROCA-HR is a targeted capture and massively parallel sequencing assay designed to detect all mutation classes including gene rearrangements, copy number variations, and gene aberrations within the Fanconi Anemia-BRCA HR, non-homologous end joining (NHEJ) DNA repair, and DNA mismatch repair pathways. BROCA-HR has been successfully used in breast and ovarian cancer pts for overall prognosis and prediction of response to platinum-based therapies. While BRCA1/2 MUT may confer survival advantage for PC pts if treated with platinum-chemotherapy, the survival impact of HRD is less well defined. Methods: We retrospectively identified 100 consecutive pts who underwent surgical resection for suspected PC at University of Washington Medical Center between 1999 and 2008. Formalin-fixed paraffin embedded resected tumors were sequenced using BROCA-HR. HRD was grouped based on the following deleterious genetic mutations: 1) BRCA1, BRCA2; 2) core HRD: BARD1, BRIP1, RAD51C, RAD51D, PALB2, CDK12, NBN; 3) non-core HRD: ATM, ATR, ATRX, BAP1, BLM, CHEK1/2, ERCC, FANC A/C/D2/E /F/G/L, MRE11, RAD50/51/51B, RIF1, SLX4; 4) HR proficient. Overall survival (OS) was measured from diagnosis until death or last follow-up. Results: 95 pts had histologically confirmed PC, and 81 pts had adequate tumor DNA for analysis. Six pts (7%) had BRCA1/2 MUT (n = 5), or BRCA1 methylation (n = 1), 1 pt (1%) had non-BRCA core HRD (PALB2 MUT), 7 pts (9%) had non-core HRD: ERCC (2), CHEK2 (2), ATR, RAD51D, and FANCA MUT (1 each). Median OS was: all pts 1.93 yrs (95% C.I. 1.53, 2.16), BRCA1/2 pts 3.09 yrs (95% CI 0.41, 12.21), all core HRD pts 1.21 yrs (95% CI 0.41, 12.21), all core and non-core HRD pts 1.89 yrs (95% CI 0.57, 4.96), HR proficient pts 1.93 yrs (95% CI 1.51, 2.15). There were no OS differences between pts with HRD vs those HR proficient. Conclusions: HRD is common (17%) but does not affect OS for pts with resected PC. Prospective clinical trials should test neo/adjuvant therapies including platinum chemotherapy and PARP inhibitors for pts with HRD.

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Abstract Details

Meeting

2020 Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session B: Hepatobiliary Cancer, Neuroendocrine/Carcinoid, Pancreatic Cancer, and Small Bowel Cancer

Track

Hepatobiliary Cancer,Neuroendocrine/Carcinoid,Pancreatic Cancer,Small Bowel Cancer,Other GI Cancer

Sub Track

Translational Research

Citation

J Clin Oncol 38, 2020 (suppl 4; abstr 732)

Abstract #

732

Poster Bd #

L21

Abstract Disclosures