Think "HER2" different: integrative diagnostic approaches for HER2-low breast cancer.

Journal: Pathologica
Published Date:

Abstract

This work explores the complex field of HER2 testing in the HER2-low breast cancer era, with a focus on methodological aspects. We aim to propose clear positions to scientific societies, institutions, pathologists, and oncologists to guide and shape the appropriate diagnostic strategies for HER2-low breast cancer. The fundamental question at hand is whether the necessary tools to effectively translate our knowledge about HER2 into practical diagnostic schemes for the lower spectrum of expression are available. Our investigation is centered on the significance of distinguishing between an immunohistochemistry (IHC) score 0 and score 1+ in light of the clinical implications now apparent, as patients with HER2-low breast cancer become eligible for trastuzumab-deruxtecan treatment. Furthermore, we discuss the definition of HER2-low beyond its conventional boundaries and assess the reliability of established diagnostic procedures designed at a time when therapeutic perspectives were non-existent for these cases. In this regard, we examine potential complementary technologies, such as gene expression analysis and liquid biopsy. Ultimately, we consider the potential role of artificial intelligence (AI) in the field of digital pathology and its integration into HER2 testing, with a particular emphasis on its application in the context of HER2-low breast cancer.

Authors

  • Caterina Marchiò
    Division of Pathology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.
  • Carmen Criscitiello
    Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan 20141, Italy; Department of Oncology and Haematology (DIPO), University of Milan, Milan 20122, Italy.
  • Cristian Scatena
  • Alfredo Santinelli
    Anatomic Pathology, Azienda Sanitaria Territoriale di Pesaro-Urbino, Pesaro, Italy.
  • Paolo Graziano
    Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, FG, Italy.
  • Umberto Malapelle
    Department of Public Health, Federico II University of Naples, Naples, Italy.
  • Giulia Cursano
    Division of Pathology, IEO, European Institute of Oncology, IRCCS, Milan, Italy.
  • Konstantinos Venetis
    Division of Pathology, IEO, European Institute of Oncology, IRCCS, Milan, Italy.
  • Giuseppe Nicolò Fanelli
    Division of Pathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
  • Francesco Pepe
    Department of Public Health, Federico II University of Naples, Naples, Italy.
  • Enrico Berrino
    Division of Pathology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.
  • Carmine De Angelis
    Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy.
  • Giuseppe Perrone
    Department of Medicine and Surgery, Research Unit of Anatomical Pathology, Università Campus Bio-Medico di Roma, Roma, Italy.
  • Giuseppe Curigliano
    Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Haematology (DIPO), University of Milan, Milan, Italy.
  • Nicola Fusco
    Biobank for Translational and Digital Medicine Unit, Division of Pathology, IEO, European Institute of Oncology IRCCS, University of Milan, Milan, 20141, Italy.