Bilateral risk reducing mastectomy uptake trends in healthy BRCA1/2 mutation carriers of an European City, the brachoice study

World Journal of Surgical Oncology https://doi.org/10.1186/s12957-026-04400-9 Article in Press Bilateral risk reducing mastectomy uptake trends in healthy BRCA1/2 mutation carriers of an European City, the brachoice study Received: 19 March 2026 Accepted: 6 May 2026 Cite this article as: Bernini M., Innocenti S., Turchetti D. et al. Bilateral risk reducing mastectomy uptake trends in healthy BRCA1/2 mutation carriers of an European City, the brachoice study. World J Surg Onc (2026). https://doi. org/10.1186/s12957-026-04400-9 A Marco Bernini, Sofia Innocenti, Daniela Turchetti, Sara Miccoli, Giovanni Innella, Alice Pellegrini, Marica Melina, Simone Zanotti, Maria Cristina Cucchi, Valentina Galluzzo, Maria Elisa Lozano Miralles, Fabrizio Ventimiglia, Daniela Cocchi & Margherita Serra E R P S S We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply. IN If this paper is publishing under a Transparent Peer Review model then Peer Review reports will publish with the final article. I T R E L C © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. ARTICLE IN PRESS BILATERAL RISK REDUCING MASTECTOMY UPTAKE TRENDS IN HEALTHY BRCA1/2 MUTATION CARRIERS OF AN EUROPEAN CITY, THE BRACHOICE STUDY. Marco Bernini*, Sofia Innocenti, Daniela Turchetti**, Sara Miccoli**, Giovanni Innella**, Alice Pellegrini*, Marica Melina*, Simone Zanotti*, Maria Cristina Cucchi***, Valentina Galluzzo***, Maria Elisa Lozano Miralles***, Fabrizio Ventimiglia***, Daniela Cocchi****, Margherita Serra*. *Breast Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna **Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna *** Breast Unit Ospedale Bellaria AUSL Bologna **** Alma mater Studiorum Universita’ di Bologna C.A. Margherita Serra Abstract S S E R P This study evaluates the uptake of bilateral risk-reducing mastectomy (BRRM) among unaffected BRCA1/2 mutation carriers in the metropolitan area of Bologna, Italy, between 2012 and 2024. Pathogenic BRCA variants, which confer a markedly increased lifetime risk of breast cancer, are managed through preventive strategies such as BRRM, which can reduce risk by more than 90%. E L C IN I T AR Among 178 women (89 BRCA1 and 89 BRCA2 carriers), 22.5% elected to undergo BRRM, with a significantly higher uptake among BRCA1 carriers (33.7%) compared with BRCA2 carriers (11.2%). Most procedures were performed more than two years after genetic testing, and the most common age at surgery was 41–45 years. Furthermore, the results demonstrate a progressive increase over time in both genetic testing and BRRM uptake, in line with international trends. However, the observed rates remain lower than those reported in Northern Europe. Despite limitations related to cohort size and data completeness, this study provides updated evidence on decision-making regarding BRRM among Italian women at hereditary risk of breast cancer. ARTICLE IN PRESS Introduction In the 1990s, the breast cancer susceptibility genes BRCA1 and BRCA2 were identified on chromosomes 17q21 and 13q12.3, respectively. Mutations in these tumor suppressor genes occur in approximately 1 in 300–500 individuals in the general population, with prevalence varying across ethnic groups; among individuals of Ashkenazi Jewish descent, the prevalence is approximately 1 in 40. Pathogenic variants (PVs) are inherited in an autosomal dominant pattern and represent a major risk factor for both breast and ovarian malignancies. BRCA1 and BRCA2 are classified as high-penetrance genes, with pathogenic variants conferring an estimated lifetime breast cancer risk of 72% and 69%, respectively. S S E R P Moreover, women carrying a BRCA PV tend to develop breast cancer at a younger age (mean age at diagnosis: 43 years for BRCA1 and 47 years for BRCA2) and have a higher likelihood of developing contralateral breast cancer compared with sporadic cases. IN It is, therefore, essential to implement and promote dedicated programs aimed at identifying and managing women with a hereditary predisposition to breast cancer. In the Emilia-Romagna region (Northern Italy), such a program has been active since 2012, offering women carrying high-penetrance mutations the opportunity to choose among different risk management strategies. E L C I T AR Among available options, bilateral risk-reducing mastectomy (BRRM) represents the most effective preventive measure, decreasing the risk of developing breast cancer by at least 90%. Furthermore, BRRM may reduce anxiety related to cancer occurrence, while still guaranteeing an adequate psychological and sexual well-being, particularly when combined with immediate breast reconstruction. However, BRRM is an invasive and irreversible intervention that does not completely eliminate cancer risk and may be associated with surgical complications. For these reasons, a thorough evaluation of risks and benefits by both patients and clinicians is essential before any decision . An international cohort study by Metcalfe et al. reported an overall BRRM uptake rate of 27.8%, with a higher propensity for surgery among women tested after 2009. The uptake of BRRM varies considerably across countries, with the highest rates observed in the United States, China, Canada, Norway, and the United Kingdom. Notably, the study included only a small Italian cohort of ten women, with data limited to the period prior to 2009. ARTICLE IN PRESS To date , no more recent studies have specifically addressed the uptake of BRRM among unaffected BRCA1/2 mutation carriers in Italy and Southern Europe. The present study stems from the BRACHOICE project, involving two metropolitan Breast Units, and aims to investigate the uptake of bilateral risk-reducing mastectomy (BRRM), as well as the age at surgery an (...truncated)