Radiation therapy management in BRCA1/2 carriers diagnosed with early breast cancer: An international cohort study

Carlotta Becherini; Eva Blondeaux; Virginia Delucchi; Luca Visani; Hee Jeong Kim; Florence Coussy; Rinat Bernstein-Molho; Antonio Di Meglio; Florentine S. Hilbers; Katarzyna Pogoda; Ava Kwong; Elisa Agostinetto; Adinda Baten; Jyoti Bajpai; Judith Balmana; Halle C.F. Moore; Ann H. Partridge; Christine Rousset-Jablonski; Kelly Anne Phillips; Angela Toss; Tiphaine Renaud; Alberta Ferrari; Fedro A. Peccatori; Lucas Sanchez; Shani Paluch-Shimon; Wanda Cui; Stephanie M. Wong; Jai Min Ryu; Robert Fruscio; Minna K. Lee; Claudio Vernieri; Alexios Matikas; Fergus J. Couch; Laura De Marchis; Maria Vittoria Dieci; Dione Aguilar-Y-Mendez; Shelley E. Hwang; Mariya Rozenblit; Deniz Can Güven; Bela Mrinakova; Nadia Harbeck; Rodrigo Sanchez-Bayona; Luca Boni; Matteo Lambertini; Icro Meattini

doi:10.1016/j.radonc.2026.111523

Radiation therapy management in BRCA1/2 carriers diagnosed with early breast cancer: An international cohort study

Carlotta Becherini
, Eva Blondeaux
, Virginia Delucchi
, Luca Visani
, Hee Jeong Kim
, Florence Coussy
, Rinat Bernstein-Molho
, Antonio Di Meglio
, Florentine S. Hilbers
, Katarzyna Pogoda
, Ava Kwong
, Elisa Agostinetto
, Adinda Baten
, Jyoti Bajpai
, Judith Balmana
, Halle C.F. Moore
, Ann H. Partridge
, Christine Rousset-Jablonski
, Kelly Anne Phillips
, Angela Toss

Tiphaine Renaud, Alberta Ferrari, Fedro A. Peccatori, Lucas Sanchez, Shani Paluch-Shimon, Wanda Cui, Stephanie M. Wong, Jai Min Ryu, Robert Fruscio, Minna K. Lee, Claudio Vernieri, Alexios Matikas, Fergus J. Couch, Laura De Marchis, Maria Vittoria Dieci, Dione Aguilar-Y-Mendez, Shelley E. Hwang, Mariya Rozenblit, Deniz Can Güven, Bela Mrinakova, Nadia Harbeck, Rodrigo Sanchez-Bayona, Luca Boni, Matteo Lambertini, Icro Meattini

Department of Surgery

Azienda Ospedaliera Careggi
University of Florence
University Eye Clinic
University of Ulsan
Institut Curie
Tel Aviv University
Gustave Roussy
Netherlands Cancer Institute
Maria Sklodowska-Curie Institute of Oncology
The University of Hong Kong
Hong Kong Hereditary Breast Cancer Family Registry
Hong Kong Sanatorium & Hospital
Université libre de Bruxelles
KU Leuven
Homi Bhabha National Institute
Vall d'Hebron Institute of Oncology
Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
Dana-Farber Cancer Institute
Centre Léon Bérard
University of Melbourne
Peter Maccallum Cancer Centre
University of Modena and Reggio Emilia
Centre Georges-François Leclerc
University of Pavia
IRCCS Istituto Europeo di Oncologia - Milano
SUMA (Grupo Cooperativo Argentino para el Estudio y la Investigación del Cáncer de Mama)
Hadassah University Medical Centre
McGill University
University of Milan - Bicocca
Azienda Ospedaliera San Gerardo Monza
Memorial Sloan-Kettering Cancer Center
IRCCS Fondazione Istituto Nazionale per lo studio e la cura dei tumori - Milano
University of Milan
Karolinska Institutet
Mayo Clinic Rochester, MN
University of Rome La Sapienza
Umberto 1 Policlinico di Roma
University of Padua
IRCCS Istituto Oncologico Veneto - Padova
Instituto Tecnologico de Estudios Superiores de Monterrey
Duke University
Yale University
Hacettepe University
Comenius University
Ludwig Maximilian University of Munich
Hospital Universitario 12 de Octubre
University of Genoa
Maastricht University

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	111523
Journal	Radiotherapy and Oncology
Volume	219
DOIs	https://doi.org/10.1016/j.radonc.2026.111523
State	Published - Jun 2026

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

BRCA
Breast cancer
Breast-conserving surgery
Loco-regional treatment
Mastectomy
Outcomes
Radiotherapy

Access to Document

10.1016/j.radonc.2026.111523

Cite this

Becherini, C., Blondeaux, E., Delucchi, V., Visani, L., Kim, H. J., Coussy, F., Bernstein-Molho, R., Di Meglio, A., Hilbers, F. S., Pogoda, K., Kwong, A., Agostinetto, E., Baten, A., Bajpai, J., Balmana, J., Moore, H. C. F., Partridge, A. H., Rousset-Jablonski, C., Phillips, K. A., ... Meattini, I. (2026). Radiation therapy management in BRCA1/2 carriers diagnosed with early breast cancer: An international cohort study. Radiotherapy and Oncology, 219, Article 111523. https://doi.org/10.1016/j.radonc.2026.111523

@article{cdf4a87aef1e46ae8cdba15bb77ea47b,

title = "Radiation therapy management in BRCA1/2 carriers diagnosed with early breast cancer: An international cohort study",

abstract = "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{\textendash}12.7), OS did not differ between BCS + RT and MS alone (adjusted hazard ratio [aHR] 1.02, 95\% CI 0.78{\textendash}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{\textendash}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.",

keywords = "BRCA, Breast cancer, Breast-conserving surgery, Loco-regional treatment, Mastectomy, Outcomes, Radiotherapy",

author = "Carlotta Becherini and Eva Blondeaux and Virginia Delucchi and Luca Visani and Kim, \{Hee Jeong\} and Florence Coussy and Rinat Bernstein-Molho and \{Di Meglio\}, Antonio and Hilbers, \{Florentine S.\} and Katarzyna Pogoda and Ava Kwong and Elisa Agostinetto and Adinda Baten and Jyoti Bajpai and Judith Balmana and Moore, \{Halle C.F.\} and Partridge, \{Ann H.\} and Christine Rousset-Jablonski and Phillips, \{Kelly Anne\} and Angela Toss and Tiphaine Renaud and Alberta Ferrari and Peccatori, \{Fedro A.\} and Lucas Sanchez and Shani Paluch-Shimon and Wanda Cui and Wong, \{Stephanie M.\} and Ryu, \{Jai Min\} and Robert Fruscio and Lee, \{Minna K.\} and Claudio Vernieri and Alexios Matikas and Couch, \{Fergus J.\} and \{De Marchis\}, Laura and Dieci, \{Maria Vittoria\} and Dione Aguilar-Y-Mendez and Hwang, \{Shelley E.\} and Mariya Rozenblit and \{Can G{\"u}ven\}, Deniz and Bela Mrinakova and Nadia Harbeck and Rodrigo Sanchez-Bayona and Luca Boni and Matteo Lambertini and Icro Meattini",

note = "Publisher Copyright: {\textcopyright} 2026 The Author(s)",

year = "2026",

month = jun,

doi = "10.1016/j.radonc.2026.111523",

language = "English",

volume = "219",

journal = "Radiotherapy and Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

}

Becherini, C, Blondeaux, E, Delucchi, V, Visani, L, Kim, HJ, Coussy, F, Bernstein-Molho, R, Di Meglio, A, Hilbers, FS, Pogoda, K, Kwong, A, Agostinetto, E, Baten, A, Bajpai, J, Balmana, J, Moore, HCF, Partridge, AH, Rousset-Jablonski, C, Phillips, KA, Toss, A, Renaud, T, Ferrari, A, Peccatori, FA, Sanchez, L, Paluch-Shimon, S, Cui, W, Wong, SM, Ryu, JM, Fruscio, R, Lee, MK, Vernieri, C, Matikas, A, Couch, FJ, De Marchis, L, Dieci, MV, Aguilar-Y-Mendez, D, Hwang, SE, Rozenblit, M, Can Güven, D, Mrinakova, B, Harbeck, N, Sanchez-Bayona, R, Boni, L, Lambertini, M & Meattini, I 2026, 'Radiation therapy management in BRCA1/2 carriers diagnosed with early breast cancer: An international cohort study', Radiotherapy and Oncology, vol. 219, 111523. https://doi.org/10.1016/j.radonc.2026.111523

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

PY - 2026/6

Y1 - 2026/6

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

UR - https://www.scopus.com/pages/publications/105035076710

U2 - 10.1016/j.radonc.2026.111523

DO - 10.1016/j.radonc.2026.111523

M3 - Article

C2 - 41941938

AN - SCOPUS:105035076710

SN - 0167-8140

VL - 219

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

M1 - 111523

ER -

Radiation therapy management in BRCA1/2 carriers diagnosed with early breast cancer: An international cohort study

Abstract

UN SDGs

Keywords

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