BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer - an observational cohort study.

Autor: Unni SK; Department of Pharmacotherapy, Pharmacotherapy Outcomes Research Center (PORC), College of Pharmacy, University of Utah, 30 South 2000 East, Rm 4834 (4th Floor), Salt Lake City, UT, 84112, USA., Schauerhamer MB; Department of Pharmacotherapy, Pharmacotherapy Outcomes Research Center (PORC), College of Pharmacy, University of Utah, 30 South 2000 East, Rm 4834 (4th Floor), Salt Lake City, UT, 84112, USA., Deka R; Department of Pharmacotherapy, Pharmacotherapy Outcomes Research Center (PORC), College of Pharmacy, University of Utah, 30 South 2000 East, Rm 4834 (4th Floor), Salt Lake City, UT, 84112, USA., Tyczynski JE; AstraZeneca Pharmaceuticals, Gaithersburg, MD, USA., Fernandes AW; AstraZeneca Pharmaceuticals, Gaithersburg, MD, USA., Stevens V; Department of Pharmacotherapy, Pharmacotherapy Outcomes Research Center (PORC), College of Pharmacy, University of Utah, 30 South 2000 East, Rm 4834 (4th Floor), Salt Lake City, UT, 84112, USA., Brixner DI; Department of Pharmacotherapy, Pharmacotherapy Outcomes Research Center (PORC), College of Pharmacy, University of Utah, 30 South 2000 East, Rm 4834 (4th Floor), Salt Lake City, UT, 84112, USA.; Program in Personalized Health Care, University of Utah, Salt Lake City, UT, USA., Stenehjem DD; Department of Pharmacotherapy, Pharmacotherapy Outcomes Research Center (PORC), College of Pharmacy, University of Utah, 30 South 2000 East, Rm 4834 (4th Floor), Salt Lake City, UT, 84112, USA. david.Stenehjem@hsc.utah.edu.; Huntsman Cancer Institute, Salt Lake City, UT, USA. david.Stenehjem@hsc.utah.edu.
Jazyk: angličtina
Zdroj: Journal of ovarian research [J Ovarian Res] 2016 Mar 22; Vol. 9, pp. 18. Date of Electronic Publication: 2016 Mar 22.
DOI: 10.1186/s13048-016-0227-x
Abstrakt: Background: Breast cancer associated (BRCA) genes are critical for DNA repair. Mutations in BRCA1 and BRCA2 (BRCAm) result in loss of these repair mechanisms and potential carcinogenesis. Germline BRCAm are common in ovarian carcinomas, particularly in platinum-sensitive disease. The increased prevalence of BRCAm in platinum-sensitive disease is likely due to enhanced responsiveness to platinum chemotherapy from homologous recombination repair deficiency. The purpose of this study was to explore BRCA testing, treatment patterns and survival in platinum-sensitive recurrent (PSR) ovarian cancer.
Methods: This was an observational cohort analysis of PSR ovarian cancer treated at the Huntsman Cancer Institute from 1995 to 2012. Germline BRCA status was ascertained through chart review and categorized as BRCAm (BRCA1/2 positive), BRCAwt (BRCA wild type or variant of uncertain significance), and untested. Treatment patterns and survival were assessed from recurrence until death or last follow-up. The Kaplan-Meier method was used to evaluate survival from recurrence by BRCA status. Logistic regression and COX proportional hazard model was used to estimate predictors of BRCA testing and survival, respectively.
Results: Of the 168 PSR patients, 15 (9 %) were BRCAm, 25 (15 %) were BRCAwt, and 128 (76 %) were untested. Median age at PSR was 56 years for BRCAm and BRCAwt (p = 0.90) and 63 years for those untested (p = 0.033 vs BRCAm). Overall survival was similar between BRCAm and BRCAwt (median 50.4 vs 67.5 months, p = 0.86) and was 24.9 months in untested patients. Significant predictors for the likelihood of BRCA testing were age (OR = 0.93, 95 % CI 0.89, 0.97, p = 0.002), family history of breast or ovarian cancer (OR = 8.33, 95 % CI: 3.08, 22.59, p < 0.001), and cancer diagnosis year (OR = 10.02, 95 % CI: 3.22, 31.21, p < 0.001). BRCA-tested patients had a lower risk of death versus untested (HR 0.35, 95 % CI 0.17, 0.68, p = 0.001).
Conclusions: BRCAwt patients had similar outcomes to BRCAm patients, potentially owing to similar age at diagnosis, representing a BRCA testing channeling bias. Younger patients, those with a family history of breast or ovarian cancer, and those diagnosed more recently were more likely to be BRCA tested. BRCA tested patients had a lower risk of death.
Databáze: MEDLINE
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