# Adjuvant CMF chemotherapy after mastectomy for node-positive breast cancer (Bonadonna 1976)

Source: https://onco.cc/key-papers/paper-bonadonna-adjuvant-cmf-nejm-1976/  
OnCo record `paper-bonadonna-adjuvant-cmf-nejm-1976` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The Milan trial that first showed chemotherapy given after breast cancer surgery reduces relapse: 5 per cent of women given CMF had relapsed after 27 months, against 24 per cent of those who were not.

## Summary

Prolonged cyclic combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF) was evaluated as adjuvant treatment after radical mastectomy in women with primary breast cancer and positive axillary nodes, at the Istituto Nazionale Tumori in Milan. After 27 months of study, relapse had occurred in 24 per cent of 179 control patients and in 5.3 per cent of 207 women given CMF (p less than one in a million), with the advantage significant in all subgroups. Women with four or more positive nodes relapsed more often, and 81.5 per cent of first relapses were at distant sites. The authors cautioned that the effect on survival and the long-term side effects were not yet known.

## Fields

- Kind: Key paper
- Last checked: 2026-11-03
- Journal: New England Journal of Medicine
- Year: 1976
- DOI: 10.1056/NEJM197602192940801
- Authors: Bonadonna G, Brusamolino E, Valagussa P, et al.
- Findings: Relapse after 27 months in 5.3 per cent of 207 women given CMF against 24 per cent of 179 controls.; The advantage was statistically significant in every subgroup analysed.; 81.5 per cent of first relapses were at distant sites.
- What it means: This is where adjuvant chemotherapy for breast cancer begins: the idea that treating the whole body after an apparently complete operation prevents cancers that would otherwise return. Anthracycline and taxane regimens later did better than CMF.
- Caveats: Early report: survival and late toxicity were unknown at the time.; Relapse reported as a crude proportion after 27 months of study, not as a time-to-event estimate.

## Sources

- N Engl J Med 1976: https://doi.org/10.1056/NEJM197602192940801
- PubMed: https://pubmed.ncbi.nlm.nih.gov/1246307/

## Connected records

- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/)
- institutions: [Fondazione IRCCS Istituto Nazionale dei Tumori](https://onco.cc/institutions/int-milan/)
- people: [Gianni Bonadonna](https://onco.cc/people/gianni-bonadonna/), [Umberto Veronesi](https://onco.cc/people/umberto-veronesi/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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