TY - JOUR
T1 - Radiation therapy management in BRCA1/2 carriers diagnosed with early breast cancer
T2 - An international cohort study
AU - Becherini, Carlotta
AU - Blondeaux, Eva
AU - Delucchi, Virginia
AU - Visani, Luca
AU - Kim, Hee Jeong
AU - Coussy, Florence
AU - Bernstein-Molho, Rinat
AU - Di Meglio, Antonio
AU - Hilbers, Florentine S.
AU - Pogoda, Katarzyna
AU - Kwong, Ava
AU - Agostinetto, Elisa
AU - Baten, Adinda
AU - Bajpai, Jyoti
AU - Balmana, Judith
AU - Moore, Halle C.F.
AU - Partridge, Ann H.
AU - Rousset-Jablonski, Christine
AU - Phillips, Kelly Anne
AU - Toss, Angela
AU - Renaud, Tiphaine
AU - Ferrari, Alberta
AU - Peccatori, Fedro A.
AU - Sanchez, Lucas
AU - Paluch-Shimon, Shani
AU - Cui, Wanda
AU - Wong, Stephanie M.
AU - Ryu, Jai Min
AU - Fruscio, Robert
AU - Lee, Minna K.
AU - Vernieri, Claudio
AU - Matikas, Alexios
AU - Couch, Fergus J.
AU - De Marchis, Laura
AU - Dieci, Maria Vittoria
AU - Aguilar-Y-Mendez, Dione
AU - Hwang, Shelley E.
AU - Rozenblit, Mariya
AU - Can Güven, Deniz
AU - Mrinakova, Bela
AU - Harbeck, Nadia
AU - Sanchez-Bayona, Rodrigo
AU - Boni, Luca
AU - Lambertini, Matteo
AU - Meattini, Icro
N1 - Funding Information:
A preliminary version of these results was presented as a selected oral communication at the European Society for Radiotherapy & Oncology ( ESTRO ) 2025 Annual Meeting, held in Vienna, Austria (2\u20136 May 2025), and published in abstract form in the Radiotherapy and Oncology ESTRO 2025 Supplement [34] . The study was partly supported by the Italian Association for Cancer Research (AIRC grant MFAG 2020 ID 24698). Dr Lambertini received support from the European Society for Medical Oncology (ESMO) for a translational research fellowship at the Institut Jules Bordet in Brussels, Belgium, at the time this study was initiated. We thank Heather Thorne, Eveline Niedermayr, all kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the many families who contribute to kConFab. kConFab is supported by a grant from the National Breast Cancer Foundation and previously by the National Health and Medical Research Council (NHMRC) , Australia, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. The kConFab Follow-Up Study is supported by Cancer Australia and the National Breast Cancer Foundation (grant PdCCRS 1100868 ), Cancer Australia (grant 809195 ), the Australian National Breast Cancer Foundation (grant IF 17), the Australian National Health and Medical Research Council , Australia (grants 454508 , 288704 , 145684 ), and the US National Institutes of Health , US (grant R01CA159868 ). KAP is an Australian National Health and Medical Research Council , Australia, Leadership Fellow. Dr Couch was supported by NIH grants R35CA253187 , P50CA116201 , and U24CA258058 , and by the Breast Cancer Research Foundation .
Funding Information:
This study did not receive specific funding for the present analysis. The work was conducted within research programmes partially supported by the Italian Association for Cancer Research (AIRC grant MFAG 2020 ID 24698). Additional institutional and collaborative support is detailed in the Acknowledgments.
Publisher Copyright:
© 2026 The Author(s)
PY - 2026/6/1
Y1 - 2026/6/1
N2 - Background: The oncological safety of breast-conserving surgery followed by radiation therapy (BCS + RT) in young women carrying pathogenic or likely pathogenic BRCA1/2 variants remains debated, with mastectomy (MS) often favoured despite limited comparative real-world evidence. We evaluated survival and recurrence outcomes associated with different loco-regional strategies in a large international cohort of young BRCA carriers. Methods: The BRCA BCY Collaboration (NCT03673306) is a retrospective, multicentre cohort including women aged = 40 years with invasive breast cancer and confirmed germline BRCA1/2 variants treated between 2000 and 2020. Outcomes were compared between patients treated with BCS + RT, MS alone, or MS plus RT (MS + RT). Endpoints were overall survival (OS), breast cancer-free interval (BCFI), and second primary breast cancer events, defined as ipsilateral breast recurrence (IBR) or contralateral breast cancer (CBC). Multivariable Cox models were used for OS and BCFI. Competing-risks models were used for IBR/CBC. Models were adjusted for prespecified prognostic factors, and subgroup analyses were conducted by BRCA gene, stage, and tumour grade. Results: Among 4,837 patients, 1,704 (35.2%) received BCS + RT, 1,488 (30.8%) MS alone, and 1,645 (34.0%) MS + RT. After a median follow-up of 8.2 years (IQR 4.8–12.7), OS did not differ between BCS + RT and MS alone (adjusted hazard ratio [aHR] 1.02, 95% CI 0.78–1.34). BCFI was comparable across groups. BCS + RT was associated with a higher risk of second primary breast cancer events compared with MS alone (aHR 1.33, 95% CI 1.07–1.66), particularly in patients with BRCA1 variants and stage III disease. Conclusion: In young BRCA1/2 carriers, BCS + RT was not associated with worse OS compared with MS alone, despite a higher risk of second primary breast events. Differences in second primary breast cancer events should be interpreted cautiously given differences in BRCA testing timing and treatment era across groups. These data support individualised loco-regional management within a multidisciplinary framework.
AB - Background: The oncological safety of breast-conserving surgery followed by radiation therapy (BCS + RT) in young women carrying pathogenic or likely pathogenic BRCA1/2 variants remains debated, with mastectomy (MS) often favoured despite limited comparative real-world evidence. We evaluated survival and recurrence outcomes associated with different loco-regional strategies in a large international cohort of young BRCA carriers. Methods: The BRCA BCY Collaboration (NCT03673306) is a retrospective, multicentre cohort including women aged = 40 years with invasive breast cancer and confirmed germline BRCA1/2 variants treated between 2000 and 2020. Outcomes were compared between patients treated with BCS + RT, MS alone, or MS plus RT (MS + RT). Endpoints were overall survival (OS), breast cancer-free interval (BCFI), and second primary breast cancer events, defined as ipsilateral breast recurrence (IBR) or contralateral breast cancer (CBC). Multivariable Cox models were used for OS and BCFI. Competing-risks models were used for IBR/CBC. Models were adjusted for prespecified prognostic factors, and subgroup analyses were conducted by BRCA gene, stage, and tumour grade. Results: Among 4,837 patients, 1,704 (35.2%) received BCS + RT, 1,488 (30.8%) MS alone, and 1,645 (34.0%) MS + RT. After a median follow-up of 8.2 years (IQR 4.8–12.7), OS did not differ between BCS + RT and MS alone (adjusted hazard ratio [aHR] 1.02, 95% CI 0.78–1.34). BCFI was comparable across groups. BCS + RT was associated with a higher risk of second primary breast cancer events compared with MS alone (aHR 1.33, 95% CI 1.07–1.66), particularly in patients with BRCA1 variants and stage III disease. Conclusion: In young BRCA1/2 carriers, BCS + RT was not associated with worse OS compared with MS alone, despite a higher risk of second primary breast events. Differences in second primary breast cancer events should be interpreted cautiously given differences in BRCA testing timing and treatment era across groups. These data support individualised loco-regional management within a multidisciplinary framework.
KW - BRCA
KW - Breast cancer
KW - Breast-conserving surgery
KW - Loco-regional treatment
KW - Mastectomy
KW - Outcomes
KW - Radiotherapy
U2 - 10.1016/j.radonc.2026.111523
DO - 10.1016/j.radonc.2026.111523
M3 - Article
SN - 0167-8140
VL - 219
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
M1 - 111523
ER -