title: The HER2 World: Better Treatment Selection for Better Outcome.
abstract: Understanding the mechanisms of trastuzumab efficacy and resistance is a step toward optimizing treatment outcome in HER2-positive breast carcinoma patients. Preclinical studies have indicated different trastuzumab antitumor mechanisms, that is, cytostatic inhibition of tumor proliferation, antibody-dependent cell cytotoxicity, and inhibition of HER2-mediated DNA repair. Clinical studies point to the clinical setting dependence of these mechanisms, with antibody-dependent cell cytotoxicity predominating when trastuzumab is used as monotherapy in neoadjuvant and metastatic settings, whereas inhibition of DNA repair predominates in neoadjuvant and adjuvant settings involving concomitant trastuzumab and chemotherapy; in sequential protocols, the antibody appears to act primarily through cytostatic activity by inhibiting HER2-mediated cell proliferation. Because the mechanisms of resistance to trastuzumab likely depend directly on those of its antitumor activity, resistance mechanisms must also be considered with respect to the different clinical settings. Moreover, the response to this reagent should be assessed according to its ability to induce tumor cytotoxic or cytostatic activity.
authors: Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy. elda.tagliabue@istitutotumori.mi.it
authors: Elda
authors: E
authors: Tagliabue
authors: Manuela
authors: M
authors: Campiglio
authors: Serenella M
authors: SM
authors: Pupa
authors: Andrea
authors: A
authors: Balsari
authors: Sylvie
authors: S
authors: Ménard
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D004260:DNA Repair / Q000187:drug effects; D018450:Disease Progression; D004357:Drug Synergism; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D020360:Neoadjuvant Therapy / Q000379:methods; D018579:Patient Selection; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab