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Article: Germline mutation in BRCA1 or MRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer

TitleGermline mutation in BRCA1 or MRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer
Authors
Issue Date2015
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/
Citation
Clinical Cancer Research, 2015, v. 21 n. 3, p. 652-657 How to Cite?
AbstractPurpose:To analyse the effect of germline mutations in BRCA1 and BRCA2 on mortality in ovarian cancer patients up to ten years after diagnosis. Experimental Design:We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival-time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analysed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analysed using Fine and Gray model. Results: The combined 10-year overall survival was 30% (95% CI, 28%-31%) for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The hazard ratio for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the hazard ratio was 0.42 at time zero and increased over time (predicted to become greater than one at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors, and to ovarian cancer specific mortality. Conclusions: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and, in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.
Persistent Identifierhttp://hdl.handle.net/10722/206832
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorCandido Dos Reis, FJen_US
dc.contributor.authorSong, Hen_US
dc.contributor.authorGoode, ELen_US
dc.contributor.authorCunningham, JMen_US
dc.contributor.authorDicks, Een_US
dc.contributor.authorMitchell, Gen_US
dc.contributor.authorMichie, Cen_US
dc.contributor.authorCass, Ien_US
dc.contributor.authorAndrulis, ILen_US
dc.contributor.authorLazaro, Cen_US
dc.contributor.authorMontagna, Men_US
dc.contributor.authorKwong, Aen_US
dc.contributor.authorNeuhausen, SLen_US
dc.contributor.authorMai, PLen_US
dc.contributor.authorToland, AEen_US
dc.contributor.authorBrenton, JDen_US
dc.contributor.authorAntoniou, ACen_US
dc.contributor.authorBowtell, DDen_US
dc.date.accessioned2014-12-02T10:06:04Z-
dc.date.available2014-12-02T10:06:04Z-
dc.date.issued2015en_US
dc.identifier.citationClinical Cancer Research, 2015, v. 21 n. 3, p. 652-657en_US
dc.identifier.urihttp://hdl.handle.net/10722/206832-
dc.description.abstractPurpose:To analyse the effect of germline mutations in BRCA1 and BRCA2 on mortality in ovarian cancer patients up to ten years after diagnosis. Experimental Design:We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival-time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analysed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analysed using Fine and Gray model. Results: The combined 10-year overall survival was 30% (95% CI, 28%-31%) for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The hazard ratio for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the hazard ratio was 0.42 at time zero and increased over time (predicted to become greater than one at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors, and to ovarian cancer specific mortality. Conclusions: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and, in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.en_US
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/en_US
dc.relation.ispartofClinical Cancer Researchen_US
dc.titleGermline mutation in BRCA1 or MRCA2 and ten-year survival for women diagnosed with epithelial ovarian canceren_US
dc.typeArticleen_US
dc.identifier.emailKwong, A: avakwong@hkucc.hku.hken_US
dc.identifier.authorityKwong, A=rp01734en_US
dc.identifier.doi10.1158/1078-0432.CCR-14-2497en_US
dc.identifier.pmcidPMC4338615-
dc.identifier.hkuros241543en_US

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