Systemic therapy in node-negative patients: updated findings from NSABP clinical trials. National Surgical Adjuvant Breast and Bowel Project.

This report updates findings from two National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trials conducted to evaluate the worth of systemic therapy for the treatment of node-negative breast cancer patients. In trial B-13, 737 women with estrogen receptor (ER)-negative tumors treated by sequential methotrexate and fluorouracil (MTX----5-FU) followed by leucovorin were compared with a control group treated by surgery alone. Findings for all patients through 5 years of follow-up indicate a 27% reduction in treatment failure as a result of MTX----5-FU (76% vs 67%). While patients 49 years old or less and 50 years old or more benefited significantly from MTX----5-FU, the effect on disease-free survival (DFS) was greatest in those 50 years or older, where a 50% reduction in treatment failure occurred (86% vs 72%). A 69% reduction in mortality resulting from MTX----5-FU was observed in the older group (95% vs 84%). Trial B-14 compared placebo with tamoxifen (TMX) in 2844 patients with ER-positive tumors. As originally reported, findings through 5 years of follow-up indicate a significant reduction (36%) in treatment failure as a result of the TMX (82% vs 72%). Improvement in DFS was highly significant in both age groups. In patients 49 years old or younger, there was a 44% reduction in DFS (81% vs 66%) and, in those 50 years old or more, a 31% reduction (82% vs 74%). A Cox proportional hazards model failed to indicate a benefit from MTX----5-FU and TMX in all patient subgroups. Both therapies reduced local-regional and distant recurrence, as well as breast tumor recurrence following lumpectomy. Updated findings from trials B-13 and B-14 continue to support our conclusions that (a) no subgroups of node-negative patients that we examined have such a good outcome as to preclude the use of effective systemic therapy in their treatment and (b) despite the benefits observed from MTX----5-FU and TMX, no subgroup of patients was so affected as to preclude use of a particular subgroup in assessing other therapy regimens in additional clinical trials. The identification and evaluation of markers to determine which patients should receive systemic therapy are of the highest priority. At present, however, the use of markers for therapeutic decision making regarding individual patients is tenuous.

RCT Entities:   Population Interventions Outcomes