title: BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer - an observational cohort study.
abstract: 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.
authors.affiliation: 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.
authors.forename: Sudhir K
authors.initials: SK
authors.lastname: Unni
authors.affiliation: 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.
authors.forename: Marisa B
authors.initials: MB
authors.lastname: Schauerhamer
authors.affiliation: 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.
authors.forename: Rishi
authors.initials: R
authors.lastname: Deka
authors.affiliation: AstraZeneca Pharmaceuticals, Gaithersburg, MD, USA.
authors.forename: Jerzy E
authors.initials: JE
authors.lastname: Tyczynski
authors.affiliation: AstraZeneca Pharmaceuticals, Gaithersburg, MD, USA.
authors.forename: Ancilla W
authors.initials: AW
authors.lastname: Fernandes
authors.affiliation: 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.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Stevens
authors.affiliation: 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.
authors.forename: Diana I
authors.initials: DI
authors.lastname: Brixner
authors.affiliation: 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.
authors.forename: David D
authors.initials: DD
authors.lastname: Stenehjem
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016190:Carboplatin / Q000494:pharmacology / Q000627:therapeutic use*; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000517:prevention & control; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D002945:Cisplatin
keywords: BRCA testing; Platinum-sensitive ovarian cancer; Survival; Systemic treatment