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

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 preva...

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Autores principales: Unni, Sudhir K., Schauerhamer, Marisa B., Deka, Rishi, Tyczynski, Jerzy E., Fernandes, Ancilla W., Stevens, Vanessa, Brixner, Diana I., Stenehjem, David D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802840/
https://www.ncbi.nlm.nih.gov/pubmed/27004793
http://dx.doi.org/10.1186/s13048-016-0227-x
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author Unni, Sudhir K.
Schauerhamer, Marisa B.
Deka, Rishi
Tyczynski, Jerzy E.
Fernandes, Ancilla W.
Stevens, Vanessa
Brixner, Diana I.
Stenehjem, David D.
author_facet Unni, Sudhir K.
Schauerhamer, Marisa B.
Deka, Rishi
Tyczynski, Jerzy E.
Fernandes, Ancilla W.
Stevens, Vanessa
Brixner, Diana I.
Stenehjem, David D.
author_sort Unni, Sudhir K.
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-016-0227-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-48028402016-03-22 BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer – an observational cohort study Unni, Sudhir K. Schauerhamer, Marisa B. Deka, Rishi Tyczynski, Jerzy E. Fernandes, Ancilla W. Stevens, Vanessa Brixner, Diana I. Stenehjem, David D. J Ovarian Res Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-016-0227-x) contains supplementary material, which is available to authorized users. BioMed Central 2016-03-22 /pmc/articles/PMC4802840/ /pubmed/27004793 http://dx.doi.org/10.1186/s13048-016-0227-x Text en © Unni et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Unni, Sudhir K.
Schauerhamer, Marisa B.
Deka, Rishi
Tyczynski, Jerzy E.
Fernandes, Ancilla W.
Stevens, Vanessa
Brixner, Diana I.
Stenehjem, David D.
BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer – an observational cohort study
title BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer – an observational cohort study
title_full BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer – an observational cohort study
title_fullStr BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer – an observational cohort study
title_full_unstemmed BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer – an observational cohort study
title_short BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer – an observational cohort study
title_sort brca testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer – an observational cohort study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802840/
https://www.ncbi.nlm.nih.gov/pubmed/27004793
http://dx.doi.org/10.1186/s13048-016-0227-x
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