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
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.