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23P - Clinical, pathological and gene expression features of HER2-low breast cancer


24 May 2020




Francesco Schettini


Annals of Oncology (2020) 31 (suppl_2): S15-S41. 10.1016/annonc/annonc117


F. Schettini1, N. Chic2, F. Brasó-Maristany1, L. Paré3, T. Pascual4, B. Conte5, O. Martinez Saez6, B. Adamo6, M. Vidal2, A. Fernandez-Martinez7, B. González-Farré8, E. Sanfeliu8, G. Perrone9, P. Villagrasa3, J. Gavila Gregori10, C.H. Barrios11, A. Lluch12, M. Martin Jimenez13, S. De Placido14, A. Prat15

Author affiliations

  • 1 Translational Genomics And Targeted Therapeutics In Solid Tumors, IDIBAPS, 08036 - Barcelona/ES
  • 2 Medical Oncology, Hospital Clinic, 08036 - Barcelona/ES
  • 3 Breast Cancer Research Group, SOLTI, 08008 - Barcelona/ES
  • 4 Department Of Genetics, University of North Carolina, Chapel Hill, ‎27599 - Chapel Hill/US
  • 5 Medical Oncology Dept., IRCCS AOU San Martino - IST-Istituto Nazionale per la Ricerca sul Cancro, 16132 - Genova/IT
  • 6 Dept. Medical Oncology, Hospital Clinic of Barcelona, 08036 - Barcelona/ES
  • 7 Genetics Department, UNC Lineberger Comprehensive Cancer Center - University of North Carolina at Chapel Hill, 27514 - Chapel Hill/US
  • 8 Pathology, Hospital Clinic of Barcelona, 08036 - Barcelona/ES
  • 9 Pathology Department, Campus Bio-Medico University, 00128 - Rome/IT
  • 10 Medical Oncology, IVO - Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 11 Medical Oncology, Centro de Pesquisa Clínica Hospital São Lucas da PUCRS, 9190580 - Porto Alegre/BR
  • 12 Medical Oncology, Hospital Clínico Universitario de Valencia, 46010 - Valencia/ES
  • 13 Dept. Servicio De Oncologia Médica, Hospital General Universitario Gregorio Marañon, 28007 - Madrid/ES
  • 14 Clinical Medicine And Surgery, University of Naples Federico II, 80100 - Naples/IT
  • 15 Medical Oncology Department, Hospital Clinic y Provincial de Barcelona, 08036 - Barcelona/ES

Abstract 23P


Novel antibody-drug conjugates against HER2 are showing high activity in clinically HER2-negative (cHER2-) breast cancer (BC) with low HER2 expression. However, the clinical and molecular features of cHER2-/HER2-low BC are yet to be elucidated.


We collected retrospective data from 8 multicenter cHER2- BC datasets, including 4 clinical trials. HER2 status in each study was determined using standard FDA-approved antibodies and ISH-techniques and classified according to the ASCO/CAP guidelines. For this study, tumors were regrouped in HER2 0 (0 score) and HER2-low (1+ or 2+ with ISH-negativity). The following variables were compared between the 2 groups in all patients and according to hormone receptor (HR) status: age, grade, ki67, histotype, tumor size, HR, HER2 and nodal status. nCounter-based PAM50 subtypes distribution and the expression of the 50 PAM50 genes, including ERBB2, were also compared.


A total of 3,136 patients with cHER2- disease (57.4% HER2-low and 42.6% HER2 0) were evaluated. Overall, 888 (28.3%) tumor samples came from metastatic sites. No statistically significant differences were found regarding clinicopathological variables between HER2-low and HER2 0. Within HR-positive (+) disease (n=2,497), 63.2% and 36.8% of tumors were HER2-low and HER2 0, respectively. Subtype distribution was similar across HR+/HER2-low and HR+/HER2 0. A total of 45/50 PAM50 genes were found differentially expressed between HR+/HER2-low and HR+/HER2 0 (False Discovery Rate [FDR]<5%). High expression of luminal (e.g. ESR1 and FOXA1) and ERBB2, and low expression of proliferation-related genes (e.g. MKI67) was found in HER2-low compared to HER2 0. Within triple negative BC (TNBC) (n=622), 34.2% were HER2-low and 65.8% were HER2 0. Subtype distribution was similar across TNBC/HER2-low and TNBC/HER2 0. No PAM50 gene was found differentially expressed between TNBC/HER2-low and TNBC/HER2 0 (FDR≥5%). Finally, ERBB2 mRNA levels were higher in HER2-low/HR+ tumors than HER2-low/TNBC (p<0.001).


HER2-low disease within clinically HER2- BC is frequent. However, significant differences exist according to HR status. Compared to HER2-low/TNBC, HER2-low/HR+ disease is a more distinct biological entity and has higher ERBB2 expression.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.


Instituto de Salud Carlos III - PI16/00904, Pas a Pas, Save the Mama, Breast Cancer Now - 2018NOVPCC1294. Fundación Científica Asociación Española Contra el Cáncer - Ayuda Postdoctoral AECC 2017. Fundación SEOM, Becas FSEOM para Formación en Investigación en Centros de Referencia en el Extranjero 2016 and 2018.


C.H. Barrios: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca, Novartis, Roche, GSK, Pfizer, Libbs, Daiichi Sankyo and MSD. A. Lluch: Research grant/Funding (self): Amgen, AstraZeneca, Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Celgene, Pierre Fabre; Advisory/Consultancy: Novartis, Pfizer, Roche/Genentech, Eisai, Celgene. M. Martin Jimenez: Research grant/Funding (self): Roche, PUMA and Novartis; Advisory/Consultancy: AstraZeneca, Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, Taiho Oncology, Daiichi Sankyo and Pfizer; Speaker Bureau/Expert testimony: AstraZeneca, Amgen, Roche/Genentech, Novartis and Pfizer. A. Prat: Honoraria (self): Pfizer, Novartis, Roche, MSD Oncology, Lilly and Daiichi Sankyo; Research grant/Funding (self): Novartis and Roche; Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol-Myers Squibb; Licensing/Royalties: patent PCT/EP2016/080056. All other authors have declared no conflicts of interest.

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