Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: an international cohort study

Eva Blondeaux; Amir Sonnenblick; Elisa Agostinetto; Raphaëlle Bas; Hee J Kim; Maria A Franzoi; Rinat Bernstein-Molho; Sabine Linn; Ava Kwong; Katarzyna Pogoda; Judith Balmana; Ann Smeets; Jyoti Bajpai; Halle C F Moore; Ann H Partridge; Kelly-Anne Phillips; Angela Toss; Christine Rousset-Jablonski; Fedro A Peccatori; Tiphaine Renaud; Alberta Ferrari; Shani Paluch-Shimon; Pablo Mando; Jeong E Lee; Robert Fruscio; Wanda Cui; Stephanie M Wong; Claudio Vernieri; Kathryn J Ruddy; Maria V Dieci; Alexios Matikas; Mariya Rozenblit; Deniz C Guven; Minna Lee; Cynthia Villarreal-Garza; Shelley E Hwang; Laura De Marchis; Fabio Puglisi; Zoe Kemp; Pedro A Meireles; Anastasia Parokonnaya; Gustavo Werutsky; Maiko Okano; Hatem A Azim; Kleida Mati; Shoshana Rosenberg; Richard Gelber; Luca Boni; Matteo Lambertini

doi:10.1016/S1470-2045(25)00152-4

Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: an international cohort study

Eva Blondeaux, Amir Sonnenblick, Elisa Agostinetto, Raphaëlle Bas, Hee J Kim, Maria A Franzoi, Rinat Bernstein-Molho, Sabine Linn, Ava Kwong, Katarzyna Pogoda, Judith Balmana, Ann Smeets, Jyoti Bajpai, Halle C F Moore, Ann H Partridge, Kelly-Anne Phillips, Angela Toss, Christine Rousset-Jablonski, Fedro A Peccatori, Tiphaine RenaudAlberta Ferrari, Shani Paluch-Shimon, Pablo Mando, Jeong E Lee, Robert Fruscio, Wanda Cui, Stephanie M Wong, Claudio Vernieri, Kathryn J Ruddy, Maria V Dieci, Alexios Matikas, Mariya Rozenblit, Deniz C Guven, Minna Lee, Cynthia Villarreal-Garza, Shelley E Hwang, Laura De Marchis, Fabio Puglisi, Zoe Kemp, Pedro A Meireles, Anastasia Parokonnaya, Gustavo Werutsky, Maiko Okano, Hatem A Azim, Kleida Mati, Shoshana Rosenberg, Richard Gelber, Luca Boni, Matteo Lambertini^*

^*Corresponding author for this work

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

Abstract

BACKGROUND: Little evidence exists on the effect of risk-reducing surgeries in young BRCA carriers with a previous history of breast cancer. We investigated the association between risk-reducing mastectomy (RRM) or risk-reducing salpingo-oophorectomy (RRSO), or both procedures, with survival outcomes in a large global cohort of young BRCA carriers with previous breast cancer.

METHODS: The BRCA BCY Collaboration is an international, hospital-based, retrospective cohort study, conducted at 109 centres in five continents, including women harbouring germline BRCA1, BRCA2, or both, pathogenic or likely pathogenic variants and diagnosed with stage I-III invasive breast cancer at the age of 40 years or younger between Jan 1, 2000, and Dec 31, 2020. The primary objectives of the present analysis were to determine the association between RRM or RRSO and overall survival in young BRCA carriers with breast cancer. The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov, NCT03673306.

FINDINGS: Between Jan 1, 2000 and Dec 31, 2020, 5290 patients were included, of whom 3361 (63·5%) patients were BRCA1 pathogenic variant carriers, 2708 (51·2%) had node-negative, and 2421 (45·8%) hormone receptor-positive breast cancer. Of 5290 patients, 2910 (55·0%) underwent RRM, 2782 (52·6%) underwent RRSO. After a median follow-up of 8·2 years (IQR 4·7-12·8), RRM was associated with significantly better overall survival compared with no RRM (adjusted HR [aHR] 0·65, 95% CI 0·53-0·78; 20-year restricted mean overall survival time 17·89 years [95% CI 17·61-18·17] with RRM vs 16·65 years [16·38-16·92] without RRM). RRSO was also associated with significantly better overall survival compared with no RRSO (aHR 0·58, 95% CI 0·48-0·71; 20-year restricted mean overall survival time 17·73 years [95% CI 17·43-18·03] with RRSO vs 16·67 years [16·38-16·96] without RRSO).

INTERPRETATION: In this global cohort of BRCA carriers with previous breast cancer diagnosis at a young age, RRM and RRSO were both associated with a significant improvement in overall survival. These findings provide evidence for a tailored counselling of a unique and high-risk patient population on cancer risk management strategies.

FUNDING: Italian Association for Cancer Research.

Original language	English
Pages (from-to)	759-770
Number of pages	12
Journal	LANCET ONCOLOGY
Volume	26
Issue number	6
Early online date	7 May 2025
DOIs	https://doi.org/10.1016/S1470-2045(25)00152-4
Publication status	Published - Jun 2025

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Blondeaux, E., Sonnenblick, A., Agostinetto, E., Bas, R., Kim, H. J., Franzoi, M. A., Bernstein-Molho, R., Linn, S., Kwong, A., Pogoda, K., Balmana, J., Smeets, A., Bajpai, J., Moore, H. C. F., Partridge, A. H., Phillips, K.-A., Toss, A., Rousset-Jablonski, C., Peccatori, F. A., ... Lambertini, M. (2025). Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: an international cohort study. LANCET ONCOLOGY, 26(6), 759-770. https://doi.org/10.1016/S1470-2045(25)00152-4

@article{16b5f7bc7a4748ad8264b4146a1ecf30,

title = "Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: an international cohort study",

abstract = "BACKGROUND: Little evidence exists on the effect of risk-reducing surgeries in young BRCA carriers with a previous history of breast cancer. We investigated the association between risk-reducing mastectomy (RRM) or risk-reducing salpingo-oophorectomy (RRSO), or both procedures, with survival outcomes in a large global cohort of young BRCA carriers with previous breast cancer.METHODS: The BRCA BCY Collaboration is an international, hospital-based, retrospective cohort study, conducted at 109 centres in five continents, including women harbouring germline BRCA1, BRCA2, or both, pathogenic or likely pathogenic variants and diagnosed with stage I-III invasive breast cancer at the age of 40 years or younger between Jan 1, 2000, and Dec 31, 2020. The primary objectives of the present analysis were to determine the association between RRM or RRSO and overall survival in young BRCA carriers with breast cancer. The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov, NCT03673306.FINDINGS: Between Jan 1, 2000 and Dec 31, 2020, 5290 patients were included, of whom 3361 (63·5%) patients were BRCA1 pathogenic variant carriers, 2708 (51·2%) had node-negative, and 2421 (45·8%) hormone receptor-positive breast cancer. Of 5290 patients, 2910 (55·0%) underwent RRM, 2782 (52·6%) underwent RRSO. After a median follow-up of 8·2 years (IQR 4·7-12·8), RRM was associated with significantly better overall survival compared with no RRM (adjusted HR [aHR] 0·65, 95% CI 0·53-0·78; 20-year restricted mean overall survival time 17·89 years [95% CI 17·61-18·17] with RRM vs 16·65 years [16·38-16·92] without RRM). RRSO was also associated with significantly better overall survival compared with no RRSO (aHR 0·58, 95% CI 0·48-0·71; 20-year restricted mean overall survival time 17·73 years [95% CI 17·43-18·03] with RRSO vs 16·67 years [16·38-16·96] without RRSO).INTERPRETATION: In this global cohort of BRCA carriers with previous breast cancer diagnosis at a young age, RRM and RRSO were both associated with a significant improvement in overall survival. These findings provide evidence for a tailored counselling of a unique and high-risk patient population on cancer risk management strategies.FUNDING: Italian Association for Cancer Research.",

author = "Eva Blondeaux and Amir Sonnenblick and Elisa Agostinetto and Rapha{\"e}lle Bas and Kim, {Hee J} and Franzoi, {Maria A} and Rinat Bernstein-Molho and Sabine Linn and Ava Kwong and Katarzyna Pogoda and Judith Balmana and Ann Smeets and Jyoti Bajpai and Moore, {Halle C F} and Partridge, {Ann H} and Kelly-Anne Phillips and Angela Toss and Christine Rousset-Jablonski and Peccatori, {Fedro A} and Tiphaine Renaud and Alberta Ferrari and Shani Paluch-Shimon and Pablo Mando and Lee, {Jeong E} and Robert Fruscio and Wanda Cui and Wong, {Stephanie M} and Claudio Vernieri and Ruddy, {Kathryn J} and Dieci, {Maria V} and Alexios Matikas and Mariya Rozenblit and Guven, {Deniz C} and Minna Lee and Cynthia Villarreal-Garza and Hwang, {Shelley E} and {De Marchis}, Laura and Fabio Puglisi and Zoe Kemp and Meireles, {Pedro A} and Anastasia Parokonnaya and Gustavo Werutsky and Maiko Okano and Azim, {Hatem A} and Kleida Mati and Shoshana Rosenberg and Richard Gelber and Luca Boni and Matteo Lambertini",

note = "Publisher Copyright: {\textcopyright} 2025 Elsevier Ltd",

year = "2025",

month = jun,

doi = "10.1016/S1470-2045(25)00152-4",

language = "English",

volume = "26",

pages = "759--770",

journal = "LANCET ONCOLOGY",

issn = "1470-2045",

publisher = "Elsevier Limited",

number = "6",

}

Blondeaux, E, Sonnenblick, A, Agostinetto, E, Bas, R, Kim, HJ, Franzoi, MA, Bernstein-Molho, R, Linn, S, Kwong, A, Pogoda, K, Balmana, J, Smeets, A, Bajpai, J, Moore, HCF, Partridge, AH, Phillips, K-A, Toss, A, Rousset-Jablonski, C, Peccatori, FA, Renaud, T, Ferrari, A, Paluch-Shimon, S, Mando, P, Lee, JE, Fruscio, R, Cui, W, Wong, SM, Vernieri, C, Ruddy, KJ, Dieci, MV, Matikas, A, Rozenblit, M, Guven, DC, Lee, M, Villarreal-Garza, C, Hwang, SE, De Marchis, L, Puglisi, F, Kemp, Z, Meireles, PA, Parokonnaya, A, Werutsky, G, Okano, M, Azim, HA, Mati, K, Rosenberg, S, Gelber, R, Boni, L & Lambertini, M 2025, 'Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: an international cohort study', LANCET ONCOLOGY, vol. 26, no. 6, pp. 759-770. https://doi.org/10.1016/S1470-2045(25)00152-4

TY - JOUR

T1 - Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer

T2 - an international cohort study

AU - Blondeaux, Eva

AU - Sonnenblick, Amir

AU - Agostinetto, Elisa

AU - Bas, Raphaëlle

AU - Kim, Hee J

AU - Franzoi, Maria A

AU - Bernstein-Molho, Rinat

AU - Linn, Sabine

AU - Kwong, Ava

AU - Pogoda, Katarzyna

AU - Balmana, Judith

AU - Smeets, Ann

AU - Bajpai, Jyoti

AU - Moore, Halle C F

AU - Partridge, Ann H

AU - Phillips, Kelly-Anne

AU - Toss, Angela

AU - Rousset-Jablonski, Christine

AU - Peccatori, Fedro A

AU - Renaud, Tiphaine

AU - Ferrari, Alberta

AU - Paluch-Shimon, Shani

AU - Mando, Pablo

AU - Lee, Jeong E

AU - Fruscio, Robert

AU - Cui, Wanda

AU - Wong, Stephanie M

AU - Vernieri, Claudio

AU - Ruddy, Kathryn J

AU - Dieci, Maria V

AU - Matikas, Alexios

AU - Rozenblit, Mariya

AU - Guven, Deniz C

AU - Lee, Minna

AU - Villarreal-Garza, Cynthia

AU - Hwang, Shelley E

AU - De Marchis, Laura

AU - Puglisi, Fabio

AU - Kemp, Zoe

AU - Meireles, Pedro A

AU - Parokonnaya, Anastasia

AU - Werutsky, Gustavo

AU - Okano, Maiko

AU - Azim, Hatem A

AU - Mati, Kleida

AU - Rosenberg, Shoshana

AU - Gelber, Richard

AU - Boni, Luca

AU - Lambertini, Matteo

PY - 2025/6

Y1 - 2025/6

N2 - BACKGROUND: Little evidence exists on the effect of risk-reducing surgeries in young BRCA carriers with a previous history of breast cancer. We investigated the association between risk-reducing mastectomy (RRM) or risk-reducing salpingo-oophorectomy (RRSO), or both procedures, with survival outcomes in a large global cohort of young BRCA carriers with previous breast cancer.METHODS: The BRCA BCY Collaboration is an international, hospital-based, retrospective cohort study, conducted at 109 centres in five continents, including women harbouring germline BRCA1, BRCA2, or both, pathogenic or likely pathogenic variants and diagnosed with stage I-III invasive breast cancer at the age of 40 years or younger between Jan 1, 2000, and Dec 31, 2020. The primary objectives of the present analysis were to determine the association between RRM or RRSO and overall survival in young BRCA carriers with breast cancer. The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov, NCT03673306.FINDINGS: Between Jan 1, 2000 and Dec 31, 2020, 5290 patients were included, of whom 3361 (63·5%) patients were BRCA1 pathogenic variant carriers, 2708 (51·2%) had node-negative, and 2421 (45·8%) hormone receptor-positive breast cancer. Of 5290 patients, 2910 (55·0%) underwent RRM, 2782 (52·6%) underwent RRSO. After a median follow-up of 8·2 years (IQR 4·7-12·8), RRM was associated with significantly better overall survival compared with no RRM (adjusted HR [aHR] 0·65, 95% CI 0·53-0·78; 20-year restricted mean overall survival time 17·89 years [95% CI 17·61-18·17] with RRM vs 16·65 years [16·38-16·92] without RRM). RRSO was also associated with significantly better overall survival compared with no RRSO (aHR 0·58, 95% CI 0·48-0·71; 20-year restricted mean overall survival time 17·73 years [95% CI 17·43-18·03] with RRSO vs 16·67 years [16·38-16·96] without RRSO).INTERPRETATION: In this global cohort of BRCA carriers with previous breast cancer diagnosis at a young age, RRM and RRSO were both associated with a significant improvement in overall survival. These findings provide evidence for a tailored counselling of a unique and high-risk patient population on cancer risk management strategies.FUNDING: Italian Association for Cancer Research.

AB - BACKGROUND: Little evidence exists on the effect of risk-reducing surgeries in young BRCA carriers with a previous history of breast cancer. We investigated the association between risk-reducing mastectomy (RRM) or risk-reducing salpingo-oophorectomy (RRSO), or both procedures, with survival outcomes in a large global cohort of young BRCA carriers with previous breast cancer.METHODS: The BRCA BCY Collaboration is an international, hospital-based, retrospective cohort study, conducted at 109 centres in five continents, including women harbouring germline BRCA1, BRCA2, or both, pathogenic or likely pathogenic variants and diagnosed with stage I-III invasive breast cancer at the age of 40 years or younger between Jan 1, 2000, and Dec 31, 2020. The primary objectives of the present analysis were to determine the association between RRM or RRSO and overall survival in young BRCA carriers with breast cancer. The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov, NCT03673306.FINDINGS: Between Jan 1, 2000 and Dec 31, 2020, 5290 patients were included, of whom 3361 (63·5%) patients were BRCA1 pathogenic variant carriers, 2708 (51·2%) had node-negative, and 2421 (45·8%) hormone receptor-positive breast cancer. Of 5290 patients, 2910 (55·0%) underwent RRM, 2782 (52·6%) underwent RRSO. After a median follow-up of 8·2 years (IQR 4·7-12·8), RRM was associated with significantly better overall survival compared with no RRM (adjusted HR [aHR] 0·65, 95% CI 0·53-0·78; 20-year restricted mean overall survival time 17·89 years [95% CI 17·61-18·17] with RRM vs 16·65 years [16·38-16·92] without RRM). RRSO was also associated with significantly better overall survival compared with no RRSO (aHR 0·58, 95% CI 0·48-0·71; 20-year restricted mean overall survival time 17·73 years [95% CI 17·43-18·03] with RRSO vs 16·67 years [16·38-16·96] without RRSO).INTERPRETATION: In this global cohort of BRCA carriers with previous breast cancer diagnosis at a young age, RRM and RRSO were both associated with a significant improvement in overall survival. These findings provide evidence for a tailored counselling of a unique and high-risk patient population on cancer risk management strategies.FUNDING: Italian Association for Cancer Research.

U2 - 10.1016/S1470-2045(25)00152-4

DO - 10.1016/S1470-2045(25)00152-4

M3 - Article

C2 - 40347973

SN - 1470-2045

VL - 26

SP - 759

EP - 770

JO - LANCET ONCOLOGY

JF - LANCET ONCOLOGY

IS - 6

ER -

Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: an international cohort study

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