{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:24:21Z","timestamp":1790742261835,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2017,6,13]],"date-time":"2017-06-13T00:00:00Z","timestamp":1497312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2017,9,15]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Breast cancer 2 (<jats:italic>BRCA2<\/jats:italic>)\u2010associated breast and ovarian cancers are sensitive to platinum\u2010based chemotherapy. It is unknown whether <jats:italic>BRCA2<\/jats:italic>\u2010associated prostate cancer responds favorably to such treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>A retrospective analysis of a single\u2010institution cohort of men with castration\u2010resistant, metastatic prostate cancer was performed to determine the association between carrier status of pathogenic <jats:italic>BRCA2<\/jats:italic> germline variants and prostate\u2010specific antigen response to carboplatin\u2010based chemotherapy. From 2001 through 2015, 8081 adult men with prostate cancer who had a consultation and\/or underwent treatment at Dana\u2010Farber Cancer Institute provided blood samples and consented to analyses of biologic material and clinical records. A subgroup of 141 men received at least 2 doses of carboplatin and docetaxel for castration\u2010resistant disease (94% were also taxane refractory). These patients were categorized according to the absence or presence of pathogenic germline mutations in <jats:italic>BRCA2<\/jats:italic> based on DNA sequencing from whole blood. The primary outcome was the response rate to carboplatin\/docetaxel chemotherapy, defined according to a decline in prostate\u2010specific antigen that exceeded 50% within 12 weeks of initiating this regimen. Associations between <jats:italic>BRCA2<\/jats:italic> mutation status and response to carboplatin\u2010based chemotherapy were tested using the Fisher exact test, with a 2\u2010sided <jats:italic>P<\/jats:italic> value &lt; .05 as the threshold for significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Pathogenic germline <jats:italic>BRCA2<\/jats:italic> variants were observed in 8 of 141 men (5.7%; 95% confidence interval, 2.5%\u201010.9%). Six of 8 <jats:italic>BRCA2<\/jats:italic> carriers (75%) experienced prostate\u2010specific antigen declines &gt;50% within 12 weeks, compared with 23 of 133 noncarriers (17%; absolute difference, 58%; 95% confidence interval, 27%\u201088%; <jats:italic>P<\/jats:italic> &lt; .001). Prostate cancer cell lines functionally corroborated these clinical findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p><jats:italic>BRCA2<\/jats:italic>\u2010associated, castration\u2010resistant prostate cancer is associated with a higher likelihood of response to carboplatin\u2010based chemotherapy than non\u2010<jats:italic>BRCA2<\/jats:italic>\u2013associated prostate cancer. <jats:bold><jats:italic>Cancer<\/jats:italic> 2017;123:3532\u20109.<\/jats:bold> \u00a9 <jats:italic>2017 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.30808","type":"journal-article","created":{"date-parts":[[2017,6,13]],"date-time":"2017-06-13T10:17:00Z","timestamp":1497349020000},"page":"3532-3539","source":"Crossref","is-referenced-by-count":228,"title":["The association between germline <scp><i>BRCA2<\/i><\/scp> variants and sensitivity to platinum\u2010based chemotherapy among men with metastatic prostate cancer"],"prefix":"10.1002","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4914-1157","authenticated-orcid":false,"given":"Mark M.","family":"Pomerantz","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Dana\u2010Farber Cancer Institute Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandor","family":"Spis\u00e1k","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Dana\u2010Farber Cancer Institute Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Urology Brigham and Women's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel M.","family":"Cronin","sequence":"additional","affiliation":[{"name":"Division of Population Sciences Dana\u2010Farber Cancer Institute Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istvan","family":"Csabai","sequence":"additional","affiliation":[{"name":"Department of Physics of Complex Systems Eotvos Lorand University Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Ledet","sequence":"additional","affiliation":[{"name":"Department of Medicine Tulane Cancer Center New Orleans Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Oliver","family":"Sartor","sequence":"additional","affiliation":[{"name":"Department of Medicine Tulane Cancer Center New Orleans Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Rainville","sequence":"additional","affiliation":[{"name":"Division of Population Sciences Dana\u2010Farber Cancer Institute Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward P.","family":"O'Connor","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Dana\u2010Farber Cancer Institute Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary T.","family":"Herbert","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Dana\u2010Farber Cancer Institute Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Sz\u00e1ll\u00e1si","sequence":"additional","affiliation":[{"name":"Department of 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