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Poster Display session 3

4377 - ERBB2 mRNA as a predictor in HER2-positive (HER2+)/hormone receptor-positive (HR+) metastatic breast cancer (BC) treated with HER2 blockade in combination with endocrine therapy (ET): a retrospective analysis of the ALTERNATIVE and SOLTI-PAMELA trials.


30 Sep 2019


Poster Display session 3


Translational Research

Tumour Site

Breast Cancer


Nuria Chic


Annals of Oncology (2019) 30 (suppl_5): v25-v54. 10.1093/annonc/mdz239


N. Chic1, T. Pascual1, F. Brasó-Maristany2, P. Villagrasa Gonzalez3, L. Pare Brunet3, F. Schettini4, B. Conte5, B. Adamo6, M. Vidal6, M. Muñoz6, O. Martínez6, B. Gonzalez-Farre7, J. Cortés8, A. Llombart-Cussac9, V. Rodrik-Outmezguine10, M.A. Izquierdo Delso11, R. Schiff12, C..K. Osborne13, M. Rimawi13, A. Prat14

Author affiliations

  • 1 Translational Genomics And Targeted Therapeutics In Solid Tumors, Institut d'Investigaciones Biomèdiques August Pi i Sunyer, 08036 - Barcelona/ES
  • 2 Oncology, Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 - Barcelona/ES
  • 3 Scientific, SOLTI, 08007 - Barcelona/ES
  • 4 Oncology, Azienda Universitaria Ospedaliera Federico II, 80131 - Napoli/IT
  • 5 Medical Oncology  , Ospedale Policlinico San Martino, University of Genova, 16132 - Genova/IT
  • 6 Medical Oncology, Hospital Clinic, 08036 - Barcelona/ES
  • 7 Pathology Department, Hospital Clinic, 08036 - Barcelona/ES
  • 8 Oncology Department, IOB Institute of Oncology, Quironsalud Group, Madrid & Barcelona & Vall d´Hebron Intitute of Oncology (VHIO), Barcelona, 28034 - Madrid/ES
  • 9 Medical Oncology, Hospital Universitario Arnau de Vilanova, 46015 - Valencia/ES
  • 10 Oncology Precision Medicine, Novartis Pharmaceuticals Corporation, 07936-1080 - East Hanover/US
  • 11 Clinical Development & Analytics, Novartis Pharma AG, 4057 - Basel/CH
  • 12 Molecular And Cellular Biology, Baylor College of Medicine, 77030 - Houston/US
  • 13 Medical Oncology, Baylor College of Medicine, 77030 - Houston/US
  • 14 Medical Oncology  , Hospital Clinic y Provincial de Barcelona, 08036 - Barcelona/ES


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Abstract 4377


The ALTERNATIVE trial randomized 355 patients (pts) with HER2+/HR+ metastatic BC to receive as 1st-line therapy lapatinib (L) + trastuzumab (T) + aromatase inhibitors (AI) or T + AI or L + AI. The neoadjuvant PAMELA trial tested a chemo-free regimen of L + T on HER2+ pts, combined with letrozole or tamoxifen in HR+ tumors. We explored the hypothesis that gene expression may help predicting benefit from anti-HER2 therapy in combination with ET.


The expression of 55 BC-related genes was evaluated from FFPE tumors using the nCounter. The PAM50 subtype distribution and the association of the expression of each gene (continuous variable) with progression-free survival (PFS) was evaluated using univariate Cox-models. Median PFS was calculated using the Kaplan-Meier method. Clinical benefit (CB) was defined as complete or partial response or stable disease at 6 months. The Cutoff Finder tool was used to find an optimal gene expression cut-off with CB as the endpoint. Logistic regression was used to evaluate the association of gene expression with pathologic complete resonse (pCR) and CB.


In ALTERNATIVE, 60 tumors (16.9%) were analyzed: 57% HER2-enriched, 20% Luminal B, 12% Luminal A, 8% Normal-like and 3% Basal-like. Median PFS in ERBB2-high group (above the median) was higher compared to ERBB2-low group (11.0 vs 5.6 months; Hazard Ratio [HazR]=0.49; p = 0.006). ERBB2 was found more expressed in pts with CB. CB rate was higher in the ERBB2-high group compared to ERBB2-low group (54% vs 22%; p = 0.013). An optimal ERBB2 mRNA cutoff (2.923) for predicting CB (AUC=0.68; odds ratio [OR]=1.49, p = 0.014; PFS HazR=0.46, p = 0.022) was then identified. The same ERBB2 cutoff in PAMELA baseline tumor samples (n = 77) was found significantly associated with pCR (43.8% in ERBB2-high vs. 11.5% in ERBB2-low; adjusted OR = 4.45; p = 0.041).


ERBB2 mRNA expression is a robust predictor of response and survival outcome in HER2+/HR+ BC following HER2-blockade and ET. Our study identifies a common biomarker between pCR improvement (OR ∼4.5) in early disease and CB in the advanced setting (PFS HazR of ∼0.50).

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS).


Has not received any funding.


N. Chic: Travel / Accommodation / Expenses: Eisai. F. Schettini: Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: Pfizer. M. Vidal: Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Daiichi Sankyo. M. Muñoz: Travel / Accommodation / Expenses: Roche. J. Cortés: Honoraria (self): Novartis; Honoraria (self): Eisai; Honoraria (self): Roche; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Celgene; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Biothera Pharmaceutical; Advisory / Consultancy: Merus; Advisory / Consultancy: Seattle Genetics. A. Llombart-Cussac: Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche/Genentech. M. Rimawi: Advisory / Consultancy: GlaxoSmithKline; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: MacroGenics; Advisory / Consultancy: Novartis; Advisory / Consultancy: Daiichi Sankyo. A. Prat: Advisory / Consultancy: Nanostring Techonologies. All other authors have declared no conflicts of interest.

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