Pancreas cancer and BRCA: A critical subset of patients with improving therapeutic outcomes Journal Article
| Authors: | Momtaz, P.; O'Connor, C. A.; Chou, J. F.; Capanu, M.; Park, W.; Bandlamudi, C.; Berger, M. F.; Kelsen, D. P.; Suehnholz, S. P.; Chakravarty, D.; Yu, K. H.; Varghese, A. M.; Zervoudakis, A.; Li, J.; Ku, G. Y.; Park, J. S.; Shcherba, M.; Harding, J. J.; Goldberg, Z.; Abou-Alfa, G. K.; Salo-Mullen, E. E.; Stadler, Z. K.; Iacobuzio-Donahue, C. A.; O’Reilly, E. M. |
| Article Title: | Pancreas cancer and BRCA: A critical subset of patients with improving therapeutic outcomes |
| Abstract: | Background: Patients with germline/somatic BRCA1/BRCA2 mutations (g/sBRCA1/2) comprise a distinct biologic subgroup of pancreas ductal adenocarcinoma (PDAC). Methods: Institutional databases were queried to identify patients who had PDAC with g/sBRCA1/2. Demographics, clinicopathologic details, genomic data (annotation sBRCA1/2 according to a precision oncology knowledge base for somatic mutations), zygosity, and outcomes were abstracted. Overall survival (OS) was estimated using the Kaplan-Meier method. Results: In total, 136 patients with g/sBRCA1/2 were identified between January 2011 and June 2020. Germline BRCA1/2 (gBRCA1/2) mutation was identified in 116 patients (85%). Oncogenic somatic BRCA1/2 (sBRCA1/2) mutation was present in 20 patients (15%). Seventy-seven patients had biallelic BRCA1/2 mutations (83%), and 16 (17%) had heterozygous mutations. Sixty-five patients with stage IV disease received frontline platinum therapy, and 52 (80%) had a partial response. The median OS for entire cohort was 27.6 months (95% CI, 24.9-34.5 months), and the median OS for patients who had stage IV disease was 23 months (95% CI, 19-26 months). Seventy-one patients received a poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor (PARPi), and 52 received PARPi monotherapy. For maintenance PARPi, 10 patients (36%) had a partial response, 12 (43%) had stable disease, and 6 (21%) had progression of disease as their best response. Six patients (21%) received maintenance PARPi for >2 years. For those with stage IV disease who received frontline platinum, the median OS was 26 months (95% CI, 20-52 months) for biallelic patients (n = 39) and 8.66 months (95% CI, 6.2 months to not reached) for heterozygous patients (n = 4). The median OS for those who received PARPi therapy was 26.5 months (95% CI, 24-53 months) for biallelic patients (n = 25) and 8.66 months (95% CI, 7.23 months to not reached) for heterozygous patients (n = 2). Conclusions: g/sBRCA1/2 mutations did not appear to have different actionable utility. Platinum and PARPi therapies offer therapeutic benefit, and very durable outcomes are observed in a subset of patients who have g/sBRCA1/2 mutations with biallelic status. © 2021 American Cancer Society |
| Keywords: | pancreas; germline; platinum; brca; somatic; zygosity; biallelic |
| Journal Title: | Cancer |
| Volume: | 127 |
| Issue: | 23 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2021-12-01 |
| Start Page: | 4393 |
| End Page: | 4402 |
| Language: | English |
| DOI: | 10.1002/cncr.33812 |
| PUBMED: | 34351646 |
| PROVIDER: | scopus |
| PMCID: | PMC9301324 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2021 -- Source: Scopus |
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