Adjuvant chemotherapy in stage II breast cancer: A brief overview of the NSABP clinical trials

Since 1972 the National Surgical Adjuvant Breast and Bowel Project (NSABP) has completed 5 adjuvant chemotherapy protocols into which over 3,500 histologically nodepositive patients have been entered; data for this review are derived predominantly from the first 3 studies. Each study was performed sequentially with the intent of identifying patient subsets responding to 1, 2, or 3 chemotherapeutic agents. Comparison of disease‐free survival in patients receiving l‐phenylalanine mustard (L‐PAM) or placebo after 10 years of follow‐up disclosed that L‐PAM was beneficial in patients up to 49 years of age, but not in women ⩾50 years. Further analysis indicated that the subset of patients ⩽49 years with 1–3 positive nodes sustained the greatest increment in disease‐free survival with single‐agent L‐PAM. The addition of 5‐fluorouracil (5‐FU) to L‐PAM was superior to L‐PAM alone in patients ⩾50 years of age, particularly those with ⩾4 positive nodes. This effect became attenuated after 6 years of follow‐up. The 3‐drug regimen of L‐PAM, 5‐FU, and methotrexate failed to provide a benefit over and above that achieved by the L‐PAM‐5‐FU combination in all subsets examined. Two further NSABP protocols are described in which the addition of Adriamycin® to L‐PAM and 5‐FU is addressed. The rationale for the current generation of NSABP adjuvant chemotherapy trials using short intensive Adriamycin® and cyclophosphamide regimens is discussed. The results continue to underscore the heterogeneous response to chemotherapy demonstrated by patient subsets characterized on the basis of age and nodal status.