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Breast Cancer · Medical Oncology · Adjuvant

NSABP B-19

In ER-negative, node-negative breast cancer, does adding cyclophosphamide to methotrexate/fluorouracil improve outcomes?

Population1,095 women with ER-negative, node-negative breast cancer.InterventionCMF.ComparatorSequential methotrexate → fluorouracil.Primary clinical outcomeDisease-free survival.

Absolute Effect

At 5 years, DFS was 82% with CMF vs 73% with MF: an absolute improvement of 9 percentage points and approximate NNT 12. Five-year survival was 88% vs 85%, a smaller and borderline difference.

Clinical interpretation

Adding cyclophosphamide produced a clear DFS gain, with the largest benefit in younger women. The survival difference at 5 years was smaller than the DFS effect.

Toxicity

Grade ≥3 toxicity was more frequent with CMF than with MF. A single dominant fixed-time toxicity endpoint suitable for a trial-level NNH is not established in the primary report.

Sources

Fisher B, et al. J Clin Oncol. 1996;14:1982–1992.

PubMed

Current-practice context · reviewed 14 October 2026

NSABP B-19 is historical evidence for adjuvant chemotherapy in node-negative ER-negative breast cancer. Modern decisions use current tumour subtype, stage, germline findings and contemporary chemotherapy regimens; the historical CMF result should not be directly translated into a present-day regimen without subtype-specific assessment.

Current guideline guidance ↗