E15. HER2 assessment in breast cancer

Abstract

Because of the important therapeutic implications, a crucial issue in breast cancer pathology is the correct identification of true HER2 positivity in tissue specimens. The relevance of such assessment on HER2-positive breast cancer patients will be further enhanced if trastuzumab is administered to patients in monotherapy, such as trastuzumab emtansine (i.e. trastuzumab-DM1, T-DM1), an antibody–drug conjugate consisting of trastuzumab linked to the cytotoxin mertansine (DM1). T-DM1 is designed to target and inhibit HER2 signaling and to deliver the chemotherapy directly inside HER2-positive cancer cells. As a consequence, it will be of utmost importance for pathologists to recognize HER2-positive carcinomas with precision, because patients will not be administered any other chemotherapeutic agents and response to treatment will rely strictly on the pathological assessment of HER2 [1]. Activation of HER2 may be driven not only by HER2 gene amplification; indeed, in terms of the biology of HER2-positive tumors, a “brand new” topic is the recent demonstration by next-generation sequencing studies of the presence of HER2 mutations in breast cancer [2]. Bose and colleagues [3] have functionally characterized 13 HER2 mutations, and seven of these mutations were activating mutations sensitive to the irreversible HER2/EGFR tyrosine kinase inhibitor neratinib [3]. Estrogen-receptor(ER-)positive breast carcinomas, either HER2-negative (score 0/1+) or showing equivocal HER2 expression (score 2+), seem to be putative candidates for HER2 mutations. Here we discuss some of the “hot topics” concerning HER2 assessment.