TY - JOUR
T1 - Characterization of HER2-low breast cancer in young women with germline BRCA1/2 pathogenetic variants
T2 - Results of a large international retrospective cohort study
AU - Schettini, Francesco
AU - Blondeaux, Eva
AU - Molinelli, Chiara
AU - Bas, Raphaëlle
AU - Kim, Hee Jeong
AU - Di Meglio, Antonio
AU - Bernstein Molho, Rinat
AU - Linn, Sabine C.
AU - Pogoda, Katarzyna
AU - Carrasco, Estela
AU - Punie, Kevin
AU - Agostinetto, Elisa
AU - Lopetegui-Lia, Nerea
AU - Phillips, Kelly Anne
AU - Toss, Angela
AU - Rousset-Jablonski, Christine
AU - Acheritogaray, Marion
AU - Ferrari, Alberta
AU - Paluch-Shimon, Shani
AU - Fruscio, Robert
AU - Cui, Wanda
AU - Wong, Stephanie M.
AU - Vernieri, Claudio
AU - Dieci, Maria Vittoria
AU - Matikas, Alexios
AU - Rozenblit, Mariya
AU - Villarreal-Garza, Cynthia
AU - De Marchis, Laura
AU - Puglisi, Fabio
AU - Vasconcelos de Matos, Leonor
AU - Mariño, Monica
AU - Teixeira, Luis
AU - Graffeo, Rossella
AU - Rognone, Alessia
AU - Chirco, Alessandra
AU - Antone, Nicoleta
AU - Abdou, Yara
AU - Marhold, Maximilian
AU - Božović-Spasojević, Ivana
AU - Cortés Salgado, Alfonso
AU - Carmisciano, Luca
AU - Bruzzone, Marco
AU - Curigliano, Giuseppe
AU - Prat, Aleix
AU - Lambertini, Matteo
N1 - Publisher Copyright:
© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.
PY - 2024/8/15
Y1 - 2024/8/15
N2 - Background: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset. Methods: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan–Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤.05. Results: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor–positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p <.001), hormone receptor–positive (p <.001), and node-positive (p =.003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p <.001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76–0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64–0.95) and overall survival (HR, 0.65; 95% CI, 0.46–0.93) in the TN subgroup. Luminal A–like tumors in HER2-low (p =.014) and TN and luminal A-like in HER2-0 (p =.019) showed the worst DFS. Conclusions: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis.
AB - Background: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset. Methods: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan–Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤.05. Results: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor–positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p <.001), hormone receptor–positive (p <.001), and node-positive (p =.003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p <.001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76–0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64–0.95) and overall survival (HR, 0.65; 95% CI, 0.46–0.93) in the TN subgroup. Luminal A–like tumors in HER2-low (p =.014) and TN and luminal A-like in HER2-0 (p =.019) showed the worst DFS. Conclusions: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis.
KW - BRCA
KW - breast cancer
KW - HER2-low
KW - subtypes
KW - young women
UR - http://www.scopus.com/inward/record.url?scp=85193250272&partnerID=8YFLogxK
U2 - 10.1002/cncr.35323
DO - 10.1002/cncr.35323
M3 - Article
C2 - 38752572
AN - SCOPUS:85193250272
SN - 0008-543X
VL - 130
SP - 2746
EP - 2762
JO - Cancer
JF - Cancer
IS - 16
ER -