{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T12:24:34Z","timestamp":1740140674859,"version":"3.37.3"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:00:00Z","timestamp":1628208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title\/>\n                  <jats:p>Familial pancreatic adenocarcinoma (PDAC) is most commonly related to inheritance of a pathogenic BRCA variant (J Med Genet 2005;42:711\u2013719). The National Comprehensive Cancer Network recommends germline testing for patients diagnosed with PDAC and recommends platinum-based chemotherapy as the preferred initial systemic therapy for patients harboring a pathogenic BRCA germline variant with PDAC (https:\/\/www.nccn.org\/guidelines\/guidelines-detail?category=1&amp;id=1455).<\/jats:p>\n                  <jats:p>PDACs related to pathogenic BRCA germline variants typically demonstrate BRCA loss of heterozygosity (LOH), which results in ineffective DNA damage repair due to a lack of normal BRCA gene product activity. By causing DNA damage, platinum-based therapies have been shown to be highly effective therapies (Cancer Cell 2010;18:499\u2013509, Gen Med 2015;17:569). In contrast, platinum-based therapies would be predicted to be significantly less effective for PDACs in patients with pathogenic BRCA germline variants who have cancers that lack BRCA LOH.<\/jats:p>\n                  <jats:p>Poly (ADP-ribose) polymerase 1 (PARP) is also key to effective DNA repair. The Food and Drug Administration has approved PARP inhibitors for patients carrying germline pathogenic BRCA variants and metastatic breast cancer or ovarian cancer (Ann Oncol 2019;30:558\u2013566, J Clin Oncol 2015;33:244\u2013250). PARP inhibitors would again be expected to be far less effective in patients who carry pathogenic BRCA germline variants with breast and ovarian cancers (those that lack BRCA LOH) than in those with BRCA-related breast and ovarian cancers (which typically demonstrate BRCA LOH), because PARP is involved in DNA repair.<\/jats:p>\n                  <jats:p>Here, we present a patient harboring a pathogenic BRCA germline variant whose PDAC grew rapidly during platinum-based therapy and lacked BRCA LOH and therefore was not likely BRCA related. Given the molecular fingerprint of BRCA-related PDAC in patients with pathogenic BRCA germline variants and the mechanism of action of platinum-based therapies and PARP inhibitors, this case underscores the importance of future studies aimed at determining whether the lack of BRCA LOH in PDACs in pathogenic BRCA germline variant carriers is a biomarker of less responsiveness to platinum-based chemotherapy and PARP inhibitors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key Points<\/jats:title>\n               <\/jats:sec>","DOI":"10.1002\/onco.13912","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T10:31:01Z","timestamp":1627295461000},"page":"916-918","source":"Crossref","is-referenced-by-count":1,"title":["Rapid Progression of Metastatic Pancreatic Adenocarcinoma During <scp>Platinum-Based<\/scp> Therapy in a Patient Harboring a Pathogenic <i>BRCA2<\/i> Germline Variant"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7408-0646","authenticated-orcid":false,"given":"Steven","family":"Sorscher","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Oncology Division, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shakti","family":"Ramkissoon","sequence":"additional","affiliation":[{"name":"Pathology and Diagnostic Medicine, Foundation Medicine, Inc, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,8,6]]},"reference":[{"key":"2022011714455855600_onco13912-bib-0001","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1136\/jmg.2004.028829","article-title":"Cancer risks in BRCA2 families: Estimates for sites other than breast and ovary","volume":"42","author":"Asperen","year":"2005","journal-title":"J Med 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