title: Adjuvant trastuzumab: a milestone in the treatment of HER-2-positive early breast cancer.
abstract: Up to one fourth of women diagnosed with early breast cancer (EBC) have tumors that are human epidermal growth factor receptor 2 (HER-2) positive. This is associated with a high risk of relapse and death from meta-static disease. Trastuzumab, a monoclonal antibody directed against the extracellular domain of HER-2, improves survival and quality of life in women with HER-2-positive metastatic breast cancer receiving chemotherapy. Four major adjuvant trials-Herceptin Adjuvant (HERA), National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31, North Central Cancer Treatment Group (NCCTG) N9831, and Breast Cancer International Research Group (BCIRG) 006-including between them >13,000 women with HER-2-positive EBC, have investigated different adjuvant treatment approaches with trastuzumab. These trials have shown that trastuzumab reduces the 3-year risk of recurrence by about half in this population. The benefit was similar across the trials despite differences in patient populations, chemotherapy regimens, and sequencing of treatment. At a 2-year follow-up, interim results from the combined analysis of the NSABP B-31 and NCCTG N9831 trials showed a one third lower mortality for trastuzumab, and there was a trend toward an overall survival benefit in the HERA and BCIRG trials. A small Finnish trial, FinHer, investigating another regimen of trastuzumab, has also shown similarly positive results. Further follow-up of the major adjuvant trials will clarify the survival benefit for women receiving trastuzumab, as well as the optimal treatment duration (1 or 2 years). Notably, cardiac events in the trastuzumab-containing arms of these trials have remained within acceptable levels, with a slightly higher (0.6%-3.3%) incidence of congestive heart failure that mostly responded to treatment. Further follow-up will provide information on long-term cardiac safety. Overall, results from clinical trials are sufficiently compelling to consider 1 year of adjuvant trastuzumab treatment for women with HER-2-positive EBC based on the risk:benefit ratio demonstrated in these studies.
authors.affiliation: Vall d'Hebron University Hospital, Oncology Service, Barcelona, Spain. jbaselga@vhebron.net
authors.forename: José
authors.initials: J
authors.lastname: Baselga
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pienkowski
authors.forename: Richard
authors.initials: R
authors.lastname: Bell
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006331:Heart Diseases / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D015337:Multicenter Studies as Topic; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009367:Neoplasm Staging; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000187:drug effects*; D013318:Stroke Volume / Q000187:drug effects; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab