TY - JOUR
T1 - Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer
AU - Schettini, Francesco
AU - Chic, Nuria
AU - Brasó-Maristany, Fara
AU - Paré, Laia
AU - Pascual, Tomás
AU - Conte, Benedetta
AU - Martínez-Sáez, Olga
AU - Adamo, Barbara
AU - Vidal, Maria
AU - Barnadas, Esther
AU - Fernández-Martinez, Aranzazu
AU - González-Farre, Blanca
AU - Sanfeliu, Esther
AU - Cejalvo, Juan Miguel
AU - Perrone, Giuseppe
AU - Sabarese, Giovanna
AU - Zalfa, Francesca
AU - Peg, Vicente
AU - Fasani, Roberta
AU - Villagrasa, Patricia
AU - Gavilá, Joaquín
AU - Barrios, Carlos H.
AU - Lluch, Ana
AU - Martín, Miguel
AU - Locci, Mariavittoria
AU - De Placido, Sabino
AU - Prat, Aleix
N1 - Funding Information:
This work was supported by the grants from the European Union’s Horizon 2020 Research and Innovation Programme under Grant agreement No. 847912 (to A.P.), the Instituto de Salud Carlos III-PI16/00904 (to A.P.), Pas a Pas (to A.P.), Save the Mama (to A.P.), Breast Cancer Now-2018NOVPCC1294 (to A.P.), Fundación Científica Asociación Española Contra el Cáncer-Ayuda Postdoctoral AECC 2017 (to F.B.-M.), Fundación SEOM, Becas FSEOM para Formación en Investigación en Centros de Referencia en el Extranjero 2018 (to T.P.) and PhD4MD - Departament de Salut expedient SLT008/18/00122 (to N.C.).
Funding Information:
A.P. has declared an immediate family member being employed by Novartis, personal honoraria from Pfizer, Novartis, Roche, MSD Oncology, Lilly and Daiichi Sankyo, travel, accommodations and expenses paid by Daiichi Sankyo, research funding from Roche and Novartis, consulting/advisory role for NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol-Myers Squibb, and patent PCT/EP2016/080056: HER2 AS A PREDICTOR OF RESPONSE TO DUAL HER2 BLOCKADE IN THE ABSENCE OF CYTOTOXIC THERAPY. C.B. declares research funding, consulting and honoraria form Astra Zeneca, Novartis, Roche, GSK, Pfizer, Libbs, Daiichi Sankyo, and MSD. A.L. declares clinical research fundings from Amgen, Astra Zeneca, Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Celgene, Pierre Fabre and advisory boards and consulting for Novartis, Pfizer, Roche/Genentech, Eisai, Celgene. M.M. declares research grants from Roche, PUMA and Novartis, consulting/advisory fees from AstraZeneca, Amgen, Taiho Oncology, Roche/ Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, Taiho Oncology, Daiichi Sankyo and Pfizer and speakers’ honoraria from AstraZeneca, Amgen, Roche/Genentech, Novartis and Pfizer. J.G. has declared speakers’ honoraria and participation in advisory boards from Pfizer, Roche, and Novartis. S.D.P. has declared honoraria from Roche, Pfizer, Astra-Zeneca, Novartis, Celgene, Eli Lilly, Amgen, and Eisai. The other authors have nothing to declare.
Publisher Copyright:
© 2021, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2021/12
Y1 - 2021/12
N2 - Novel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.
AB - Novel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.
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U2 - 10.1038/s41523-020-00208-2
DO - 10.1038/s41523-020-00208-2
M3 - Article
AN - SCOPUS:85098711584
VL - 7
JO - npj Breast Cancer
JF - npj Breast Cancer
SN - 2374-4677
IS - 1
M1 - 1
ER -