title: Management of small HER2 overexpressing tumours.
abstract: Overexpression of the human epidermal growth factor receptor 2 (HER2) is found in 10-20 % of breast cancers and is associated with a worse prognosis. Several large studies have established the addition of trastuzumab to chemotherapy as the gold standard in early breast cancer that overexpresses HER2. Little is known about the role of such adjuvant treatment in node-negative subcentimeter tumours ('small tumours', pT1a/b) because these patients were generally excluded from the pivotal trials. Only the BCIRG006 study published in 2011 included such tumours if high-risk features were present. Here we review the literature of small HER2-positive tumours and present a meta-analysis of retrospective studies confirming a worse outcome in terms of disease-free survival (hazard ratio 2.6, p < 0.001) and a trend for higher odds of distant recurrence at 5 years (odds ratio [OR] 2.51, p = 0.11). We discuss these findings in the light of the increased risk of grade 3 and 4 cardiac toxicity (OR 7.6, p < 0.001) and other adverse events associated with the use of trastuzumab. Such treatment may well be a valuable option in selected patients with high-risk features but physicians should exercise caution given the small absolute benefits of adjuvant chemotherapy and trastuzumab for patients with small HER2-overexpressing tumours.
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Hospital, Department of Medicine, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada.
authors.forename: Arnoud
authors.initials: A
authors.lastname: Templeton
authors.forename: Alberto
authors.initials: A
authors.lastname: Ocaña
authors.forename: Boštjan
authors.initials: B
authors.lastname: Seruga
authors.forename: Francisco
authors.initials: F
authors.lastname: Vera-Badillo
authors.forename: Lindsay
authors.initials: L
authors.lastname: Carlsson
authors.forename: Philippe
authors.initials: P
authors.lastname: Bedard
authors.forename: Eitan
authors.initials: E
authors.lastname: Amir
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human