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HER2-enriched subtype and pathological complete response in HER2-positive breast cancer: A systematic review and meta-analysis

  • Author Footnotes
    1 Co-first authors for equal contribution.
    Francesco Schettini
    Footnotes
    1 Co-first authors for equal contribution.
    Affiliations
    Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy

    Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain

    SOLTI Breast Cancer Research Group, Barcelona, Spain
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  • Author Footnotes
    1 Co-first authors for equal contribution.
    Tomás Pascual
    Footnotes
    1 Co-first authors for equal contribution.
    Affiliations
    Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain

    SOLTI Breast Cancer Research Group, Barcelona, Spain

    Department of Medical Oncology, Hospital Clínic, Barcelona, Spain
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  • Benedetta Conte
    Affiliations
    Department of Medical Oncology, Ospedale Policlinico San Martino, University of Genova, Genova, Italy
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  • Nuria Chic
    Affiliations
    SOLTI Breast Cancer Research Group, Barcelona, Spain

    Department of Medical Oncology, Hospital Clínic, Barcelona, Spain
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  • Fara Brasó-Maristany
    Affiliations
    Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain

    Department of Medical Oncology, Hospital Clínic, Barcelona, Spain
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  • Patricia Galván
    Affiliations
    Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain
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  • Olga Martínez
    Affiliations
    Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain

    Department of Medical Oncology, Hospital Clínic, Barcelona, Spain
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  • Barbara Adamo
    Affiliations
    Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain

    SOLTI Breast Cancer Research Group, Barcelona, Spain

    Department of Medical Oncology, Hospital Clínic, Barcelona, Spain
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  • Maria Vidal
    Affiliations
    Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain

    SOLTI Breast Cancer Research Group, Barcelona, Spain

    Department of Medical Oncology, Hospital Clínic, Barcelona, Spain
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  • Montserrat Muñoz
    Affiliations
    Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain

    SOLTI Breast Cancer Research Group, Barcelona, Spain

    Department of Medical Oncology, Hospital Clínic, Barcelona, Spain
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  • Aranzazu Fernández-Martinez
    Affiliations
    Department of Genetics, University of North Carolina, Chapel Hill, USA
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  • Carla Rognoni
    Affiliations
    Centre for Research on Health and Social Care Management (CERGAS), SDA Bocconi School of Management, Milan, Italy
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  • Gaia Griguolo
    Affiliations
    Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy

    Division of Medical Oncology 2, Istituto Oncologico Veneto – IRCCSS, Padova, Italy
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  • Valentina Guarneri
    Affiliations
    Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy

    Division of Medical Oncology 2, Istituto Oncologico Veneto – IRCCSS, Padova, Italy
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  • Pier Franco Conte
    Affiliations
    Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy

    Division of Medical Oncology 2, Istituto Oncologico Veneto – IRCCSS, Padova, Italy
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  • Mariavittoria Locci
    Affiliations
    Department of Neuroscience, Reproductive Medicine, Odontostomatology, University of Naples Federico II, Naples, Italy
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  • Jan C. Brase
    Affiliations
    Novartis Pharma AG, Basel, Switzerland
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  • Blanca Gonzalez-Farre
    Affiliations
    Department of Pathology, Hospital Clinic, Barcelona, Spain
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  • Patricia Villagrasa
    Affiliations
    SOLTI Breast Cancer Research Group, Barcelona, Spain
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  • Sabino De Placido
    Affiliations
    Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
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  • Rachel Schiff
    Affiliations
    Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA

    Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
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  • Jamunarani Veeraraghavan
    Affiliations
    Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA
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  • Mothaffar F. Rimawi
    Affiliations
    Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA

    Department of Medicine, Baylor College of Medicine, Houston, TX, USA
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  • C. Kent Osborne
    Affiliations
    Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA

    Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
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  • Sonia Pernas
    Affiliations
    SOLTI Breast Cancer Research Group, Barcelona, Spain

    Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Department of Medical Oncology, Institut Català d'Oncologia-H. U. Bellvitge-IDIBELL, Barcelona, Spain
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  • Charles M. Perou
    Affiliations
    Department of Genetics, University of North Carolina, Chapel Hill, USA
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  • Lisa A. Carey
    Affiliations
    Department of Medicine, University of North Carolina, Chapel Hill, USA
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  • Aleix Prat
    Correspondence
    Corresponding author at: Translational Genomic and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and Department of Medical Oncology, Hospital Clinic, Carrer de Villarroel, 170, 08036 Barcelona, Spain.
    Affiliations
    Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain

    SOLTI Breast Cancer Research Group, Barcelona, Spain

    Department of Medical Oncology, Hospital Clínic, Barcelona, Spain
    Search for articles by this author
  • Author Footnotes
    1 Co-first authors for equal contribution.
Published:January 17, 2020DOI:https://doi.org/10.1016/j.ctrv.2020.101965

      Highlights

      • We correlated the breast cancer intrinsic subtypes with pCR in HER2+ disease.
      • The HER2-E subtype was significantly and consistently associated with pCR after anti-HER2-based therapy.
      • The HER2-E subtype was associated with pCR irrespective of hormone receptor status.
      • The HER2-E subtype was associated with pCR also with chemo-free neoadjuvant schemes.

      Abstract

      Background

      HER2-positive (HER2+) breast cancer (BC) comprises all the four PAM50 molecular subtypes. Among these, the HER2-Enriched (HER2-E) appear to be associated with higher pathological complete response (pCR) rates following anti-HER2-based regimens. Here, we present a meta-analysis to validate the association of the HER2-E subtype with pCR following anti-HER2-based neoadjuvant treatments with or without chemotherapy (CT).

      Methods

      A systematic literature search was performed in February 2019. The primary objective was to compare the association between HER2-E subtype (versus others) and pCR. Selected secondary objectives were to compare the association between 1) HER2-E subtype and pCR in CT-free studies, 2) HER2-E subtype within hormone receptor (HR)-negative and HR+ disease and 3) HR-negative disease (versus HR+) and pCR in all patients and within HER2-E subtype. A random-effect model was applied. The Higgins’ I2 was used to quantify heterogeneity.

      Results

      Sixteen studies were included, 5 of which tested CT-free regimens. HER2-E subtype was significantly associated with pCR in all patients (odds ratio [OR] = 3.50, p < 0.001, I2 = 33%), in HR+ (OR = 3.61, p < 0.001, I2 = 1%) and HR-negative tumors (OR = 2.28, p = 0.01, I2 = 47%). In CT-free studies, HER2-E subtype was associated with pCR in all patients (OR = 5.52, p < 0.001, I2 = 0%) and in HR + disease (OR = 4.08, p = 0.001, I2 = 0%). HR-negative status was significantly associated with pCR compared to HR + status in all patients (OR = 2.41, p < 0.001, I2 = 30%) and within the HER2-E subtype (OR = 1.76, p < 0.001, I2 = 0%).

      Conclusions

      The HER2-E biomarker identifies patients with a higher likelihood of achieving a pCR following neoadjuvant anti-HER2-based therapy beyond HR status and CT use. Future trial designs to escalate or de-escalate systemic therapy in HER2+ disease should consider this genomic biomarker.

      Keywords

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