Prophylactic Interventions for Hereditary Breast and Ovarian Cancer Risks and Mortality in BRCA1/2 Carriers

Author:

Liu Taoran1ORCID,Yu Jing1,Gao Yangyang1,Ma Xinyang1,Jiang Shan2ORCID,Gu Yuanyuan2ORCID,Ming Wai-kit1ORCID

Affiliation:

1. Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong 999077, China

2. Macquarie University Centre for the Health Economy, Macquarie Business School and Australian Institute of Health Innovation, Macquarie University, Sydney, NSW 2109, Australia

Abstract

Background: Hereditary breast and ovarian cancers (HBOCs) pose significant health risks worldwide and are mitigated by prophylactic interventions. However, a meta-analysis of their efficacy and the impact of different genetic variants on their effectiveness is lacking. Methods: A systematic review and meta-analysis were conducted, adhering to Cochrane guidelines. The review encompassed studies that involved prophylactic interventions for healthy women with BRCA variants, focusing on cancer incidence and mortality outcomes. The Newcastle–Ottawa Scale was used for risk of bias assessment. We pooled the extracted outcomes using random effects models and conducted subgroup analyses stratified by intervention, variant, and cancer types. Results: A total of 21 studies met the inclusion criteria. The meta-analysis revealed that prophylactic interventions significantly reduced cancer risk and mortality. The subgroup analysis showed a greater protective effect for BRCA2 than BRCA1 variant carriers. Risk-reducing surgeries (RRS) were more effective than chemoprevention, with RRS notably reducing cancer risk by 56% compared to 39% for chemoprevention. Prophylactic oophorectomy significantly reduced HBOC risks, while the effect of prophylactic mastectomy and chemoprevention on mortality was less conclusive. Conclusions: Prophylactic interventions significantly reduce the risk of HBOC and associated mortality. This comprehensive analysis provides insights for future economic evaluations and clinical decision-making in HBOC interventions.

Funder

SIRG—the CityU Strategic Interdisciplinary Research Grant

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference54 articles.

1. American Cancer Society (2023). Breast Cancer Statistics|How Common Is Breast Cancer, American Cancer Society.

2. American Cancer Society (2023). Ovarian Cancer Statistics|How Common is Ovarian Cancer, American Cancer Society.

3. WCRF International (2022). Ovarian Cancer Statistics|World Cancer Research Fund International, WCRF International.

4. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families;Ford;Am. J. Hum. Genet.,1998

5. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2;King;Science,2003

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