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Prevalence and clinical impact of tumor BRCA1 and BRCA2 mutations in patients presenting with localized or metastatic hormone-sensitive prostate cancer

Prostate Cancer and Prostatic Diseases volume 25, pages 199–207 (2022)Cite this article

Subjects

Abstract

Background

The appropriate management of localized or metastatic hormone-sensitive prostate cancer (HSPC) patients harboring tumor BRCA mutations (tBRCAm) is not well-characterized. We sought to evaluate the prevalence and clinical outcomes of patients with tBRCAm and localized or de novo metastatic HSPC.

Methods

We performed a multicenter, international, retrospective cohort study of localized (cohort 1) and de novo metastatic (cohort 2) HSPC patients who underwent tumor BRCA1 and BRCA2 sequencing from 2013 to 2019. Primary endpoints included event-free survival (EFS) and metastases-free survival (MFS) for cohort 1, and time to castration-resistant prostate cancer (TTCRPC) and overall survival (OS) for cohort 2. Kaplan–Meier method and Cox regression models estimated the association of endpoints with tBRCA status.

Results

Of 399 identified patients with localized and de novo metastatic HSPC who underwent tumor BRCA1 and BRCA2 sequencing, 3.1% (8/258) patients of cohort 1 and 10.6% (15/141) patients of cohort 2 harbored tBRCAm. The median follow-up was 33 and 36 months, respectively. In cohort 1, median EFS was 18.1 vs. 57 months (p = 0.28) and MFS was 37 vs. 153.4 months (p = 0.08) for patients with tBRCAm compared to patients with no tBRCAm. In cohort 2, the TTCRPC was 24 vs. 19 months (p = 0.65) and OS was 64 vs. 60 months (p = 0.95) in patients with and without tBRCAm, respectively.

Conclusions

While tBRCAm seems to be associated with greater relapse risk in localized disease, tBRCAm did not influence the clinical outcomes of patients presenting with de novo metastatic HSPC treated with conventional therapies. tBRCAm may exert different prognostic effects across the clinical spectrum of prostate cancer.

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Fig. 1: Study diagram.
Fig. 2
Fig. 3: Frequencies of tumor BRCA1 and BRCA2 alterations in select studies across the clinical spectrum of prostate cancer.

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Authors and Affiliations

  1. Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium

    Nieves Martinez Chanza, Marianne Paesmans, Daphne T’Kint de Roodenbeke, Thierry Gil, Spyridon Sideris & Thierry Roumeguere

  2. Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium

    Nieves Martinez Chanza, Anna Accarain, Laurence Desmyter, Spyridon Sideris & Thierry Roumeguere

  3. Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    Brandon Bernard, Anis A. Hamid & Christopher J. Sweeney

  4. Institut de Cancérologie Strasbourg Europe (ICANS), Strasbourg, France

    Philippe Barthelemy

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Contributions

Conception and design: NMC, BB, AAH, and CJS. Acquisition of data: NMC, BB, PB, AA, and AAH. Analysis and interpretation of data: NMC, BB, AAH, and CJS. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: MP and AAH. Supervision: AAH and CJS.

Corresponding author

Correspondence to Nieves Martinez Chanza.

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Conflict of interest

NMC reports support for research travel from Pfizer, Janssen and Ipsen, and consulting fees for BMS, Pfizer, Sanofi, and Bayer. TR reported supports for reseach travel from Janssen and consulting fees for BMS, Pfizer, MSD, and Astellas. Disclosure statement for CJS, MBBS: Consulting or Advisory Role: Sanofi, Janssen, Astellas Pharma, Bayer, Genentech, AstraZeneca, Pfizer, Lilly, Research Funding: Janssen Biotech (Inst), Astellas Pharma (Inst), Sanofi (Inst), Bayer (Inst), Dendreon (Inst); Patents, Royalties, Other Intellectual Property: Pathenolide (Indiana University): dimethylaminoparthenolide (Leuchemix); Exelixis: Abiraterone plus cabozantinib combination. Stock or Other Ownership: Leuchemix. Other authors do not declare any conflict of interest.

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Martinez Chanza, N., Bernard, B., Barthelemy, P. et al. Prevalence and clinical impact of tumor BRCA1 and BRCA2 mutations in patients presenting with localized or metastatic hormone-sensitive prostate cancer. Prostate Cancer Prostatic Dis 25, 199–207 (2022). https://doi.org/10.1038/s41391-021-00397-2

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