Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants

Matteo Lambertini; Marcello Ceppi; Anne Sophie Hamy; Olivier Caron; Philip D. Poorvu; Estela Carrasco; Albert Grinshpun; Kevin Punie; Christine Rousset-Jablonski; Alberta Ferrari; Shani Paluch-Shimon; Angela Toss; Claire Senechal; Fabio Puglisi; Katarzyna Pogoda; Jose Alejandro Pérez-Fidalgo; Laura De Marchis; Riccardo Ponzone; Luca Livraghi; Maria Del Pilar Estevez-Diz; Cynthia Villarreal-Garza; Maria Vittoria Dieci; Florian Clatot; Francois P. Duhoux; Rossella Graffeo; Luis Teixeira; Octavi Córdoba; Amir Sonnenblick; Arlindo R. Ferreira; Ann H. Partridge; Antonio Di Meglio; Claire Saule; Fedro A. Peccatori; Marco Bruzzone; Marie Daphne t’Kint de Roodenbeke; Lieveke Ameye; Judith Balmaña; Lucia Del Mastro; Hatem A. Azim

doi:10.1038/s41523-021-00224-w

Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants

Matteo Lambertini, Marcello Ceppi, Anne Sophie Hamy, Olivier Caron, Philip D. Poorvu, Estela Carrasco, Albert Grinshpun, Kevin Punie, Christine Rousset-Jablonski, Alberta Ferrari, Shani Paluch-Shimon, Angela Toss, Claire Senechal, Fabio Puglisi, Katarzyna Pogoda, Jose Alejandro Pérez-Fidalgo, Laura De Marchis, Riccardo Ponzone, Luca Livraghi, Maria Del Pilar Estevez-DizCynthia Villarreal-Garza, Maria Vittoria Dieci, Florian Clatot, Francois P. Duhoux, Rossella Graffeo, Luis Teixeira, Octavi Córdoba, Amir Sonnenblick, Arlindo R. Ferreira, Ann H. Partridge, Antonio Di Meglio, Claire Saule, Fedro A. Peccatori, Marco Bruzzone, Marie Daphne t’Kint de Roodenbeke, Lieveke Ameye, Judith Balmaña, Lucia Del Mastro, Hatem A. Azim

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

22 Citations (Scopus)

Abstract

Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR−]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I–III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60–0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94–2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients’ counseling on treatment, prevention, and surveillance strategies.

Original language	English
Article number	16
Journal	npj Breast Cancer
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41523-021-00224-w
Publication status	Published - 1 Dec 2021

Access to Document

10.1038/s41523-021-00224-w

Cite this

Lambertini, M., Ceppi, M., Hamy, A. S., Caron, O., Poorvu, P. D., Carrasco, E., Grinshpun, A., Punie, K., Rousset-Jablonski, C., Ferrari, A., Paluch-Shimon, S., Toss, A., Senechal, C., Puglisi, F., Pogoda, K., Pérez-Fidalgo, J. A., De Marchis, L., Ponzone, R., Livraghi, L., ... Azim, H. A. (2021). Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants. npj Breast Cancer, 7(1), Article 16. https://doi.org/10.1038/s41523-021-00224-w

@article{8e9f74c2ced84a8ca3870f16afac0ee3,

title = "Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants",

abstract = "Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR−]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I–III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60–0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94–2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients{\textquoteright} counseling on treatment, prevention, and surveillance strategies.",

author = "Matteo Lambertini and Marcello Ceppi and Hamy, {Anne Sophie} and Olivier Caron and Poorvu, {Philip D.} and Estela Carrasco and Albert Grinshpun and Kevin Punie and Christine Rousset-Jablonski and Alberta Ferrari and Shani Paluch-Shimon and Angela Toss and Claire Senechal and Fabio Puglisi and Katarzyna Pogoda and P{\'e}rez-Fidalgo, {Jose Alejandro} and {De Marchis}, Laura and Riccardo Ponzone and Luca Livraghi and Estevez-Diz, {Maria Del Pilar} and Cynthia Villarreal-Garza and Dieci, {Maria Vittoria} and Florian Clatot and Duhoux, {Francois P.} and Rossella Graffeo and Luis Teixeira and Octavi C{\'o}rdoba and Amir Sonnenblick and Ferreira, {Arlindo R.} and Partridge, {Ann H.} and {Di Meglio}, Antonio and Claire Saule and Peccatori, {Fedro A.} and Marco Bruzzone and {t{\textquoteright}Kint de Roodenbeke}, {Marie Daphne} and Lieveke Ameye and Judith Balma{\~n}a and {Del Mastro}, Lucia and Azim, {Hatem A.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

day = "1",

doi = "10.1038/s41523-021-00224-w",

language = "English",

volume = "7",

journal = "npj Breast Cancer",

issn = "2374-4677",

number = "1",

}

Lambertini, M, Ceppi, M, Hamy, AS, Caron, O, Poorvu, PD, Carrasco, E, Grinshpun, A, Punie, K, Rousset-Jablonski, C, Ferrari, A, Paluch-Shimon, S, Toss, A, Senechal, C, Puglisi, F, Pogoda, K, Pérez-Fidalgo, JA, De Marchis, L, Ponzone, R, Livraghi, L, Estevez-Diz, MDP, Villarreal-Garza, C, Dieci, MV, Clatot, F, Duhoux, FP, Graffeo, R, Teixeira, L, Córdoba, O, Sonnenblick, A, Ferreira, AR, Partridge, AH, Di Meglio, A, Saule, C, Peccatori, FA, Bruzzone, M, t’Kint de Roodenbeke, MD, Ameye, L, Balmaña, J, Del Mastro, L & Azim, HA 2021, 'Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants', npj Breast Cancer, vol. 7, no. 1, 16. https://doi.org/10.1038/s41523-021-00224-w

TY - JOUR

T1 - Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants

AU - Lambertini, Matteo

AU - Ceppi, Marcello

AU - Hamy, Anne Sophie

AU - Caron, Olivier

AU - Poorvu, Philip D.

AU - Carrasco, Estela

AU - Grinshpun, Albert

AU - Punie, Kevin

AU - Rousset-Jablonski, Christine

AU - Ferrari, Alberta

AU - Paluch-Shimon, Shani

AU - Toss, Angela

AU - Senechal, Claire

AU - Puglisi, Fabio

AU - Pogoda, Katarzyna

AU - Pérez-Fidalgo, Jose Alejandro

AU - De Marchis, Laura

AU - Ponzone, Riccardo

AU - Livraghi, Luca

AU - Estevez-Diz, Maria Del Pilar

AU - Villarreal-Garza, Cynthia

AU - Dieci, Maria Vittoria

AU - Clatot, Florian

AU - Duhoux, Francois P.

AU - Graffeo, Rossella

AU - Teixeira, Luis

AU - Córdoba, Octavi

AU - Sonnenblick, Amir

AU - Ferreira, Arlindo R.

AU - Partridge, Ann H.

AU - Di Meglio, Antonio

AU - Saule, Claire

AU - Peccatori, Fedro A.

AU - Bruzzone, Marco

AU - t’Kint de Roodenbeke, Marie Daphne

AU - Ameye, Lieveke

AU - Balmaña, Judith

AU - Del Mastro, Lucia

AU - Azim, Hatem A.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR−]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I–III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60–0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94–2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients’ counseling on treatment, prevention, and surveillance strategies.

AB - Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR−]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I–III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60–0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94–2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients’ counseling on treatment, prevention, and surveillance strategies.

UR - http://www.scopus.com/inward/record.url?scp=85100856047&partnerID=8YFLogxK

U2 - 10.1038/s41523-021-00224-w

DO - 10.1038/s41523-021-00224-w

M3 - Article

AN - SCOPUS:85100856047

SN - 2374-4677

VL - 7

JO - npj Breast Cancer

JF - npj Breast Cancer

IS - 1

M1 - 16

ER -

Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants

Abstract

Access to Document

Other files and links

Cite this