HER2 and choice of adjuvant chemotherapy for invasive breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-15

Citation
S. Paik et al., HER2 and choice of adjuvant chemotherapy for invasive breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-15, J NAT CANC, 92(24), 2000, pp. 1991-1998
Citations number
14
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Volume
92
Issue
24
Year of publication
2000
Pages
1991 - 1998
Database
ISI
SICI code
Abstract
Background: Recent retrospective analyses have suggested that breast cancer patients whose tumors overexpress HER2 derive preferential benefit from tr eatment with anthracyclines such as doxorubicin. This has led some clinicia ns to propose that HER2 should be used as a predictive marker in choosing b etween anthracycline-based regimens and combination chemotherapy with cyclo phosphamide, methotrexate, and 5-fluorouracil (CMF). We evaluated this reco mmendation in a retrospective study of National Surgical Adjuvant Breast an d Bowel Project Protocol B-15, in which patients received a combination of doxorubicin and cyclophosphamide (AC), CMF, or AC followed by CMF, We hypot hesized that AC would be superior to CMF only in the HER2-positive patients . Methods: Immunohistochemical detection of HER2 was performed on tumor sec tions from 2034 of 2295 eligible patients. We used statistical analysis to evaluate the interaction between the efficacy of the assigned treatments an d HER2 overexpression. All statistical tests were two-sided. Results: Tumor sections from 599 patients (29%) stained positive for HER2. AC was superio r to CMF in HER2-positive patients only, although differences in outcomes d id not reach statistical significance. In the HER2-positive cohort, relativ e risks of failure (i.e., after AC treatment as compared with CMF treatment ) were 0.84 for disease-free survival (DFS) (95% confidence interval [CI] = 0.65-1.07; P = .15), 0.82 for survival (95% CT = 0.63-1.06; p = .14), and 0.80 for recurrence-free survival (RFS) (95% CI = 0.62-1.04; P = .10). Test s for interaction between treatment and HER2 status were suggestive but not statistically significant (P = .19 for DFS, P = .11 for survival, and P = .08 for RFS), Conclusions: These results, together with overview results in dicating minor overall superiority for anthracycline-based regimens relativ e to CMF, indicate a preference for the AC regimen in patients with HER2-po sitive tumors. Both AC and CMF regimens may be considered for patients with HER2-negative tumors.