Summary
Background
Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks
of both recurrence and breast cancer mortality in all women with node-positive disease
considered together. However, the benefit in women with only one to three positive
lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women
after mastectomy and axillary dissection.
Methods
We did a meta-analysis of individual data for 8135 women randomly assigned to treatment
groups during 1964–86 in 22 trials of radiotherapy to the chest wall and regional
lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy.
Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses
were stratified by trial, individual follow-up year, age at entry, and pathological
nodal status.
Findings
3786 women had axillary dissection to at least level II and had zero, one to three,
or four or more positive nodes. All were in trials in which radiotherapy included
the chest wall, supraclavicular or axillary fossa (or both), and internal mammary
chain. For 700 women with axillary dissection and no positive nodes, radiotherapy
had no significant effect on locoregional recurrence (two-sided significance level
[2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76–1·48,
2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89–1·55, 2p>0·1). For 1314
women with axillary dissection and one to three positive nodes, radiotherapy reduced
locoregional recurrence (2p<0·00001), overall recurrence (RR 0·68, 95% CI 0·57–0·82,
2p=0·00006), and breast cancer mortality (RR 0·80, 95% CI 0·67–0·95, 2p=0·01). 1133
of these 1314 women were in trials in which systemic therapy (cyclophosphamide, methotrexate,
and fluorouracil, or tamoxifen) was given in both trial groups and, for them, radiotherapy
again reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·67, 95%
CI 0·55–0·82, 2p=0·00009), and breast cancer mortality (RR 0·78, 95% CI 0·64–0·94,
2p=0·01). For 1772 women with axillary dissection and four or more positive nodes,
radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR
0·79, 95% CI 0·69–0·90, 2p=0·0003), and breast cancer mortality (RR 0·87, 95% CI 0·77–0·99,
2p=0·04).
Interpretation
After mastectomy and axillary dissection, radiotherapy reduced both recurrence and
breast cancer mortality in the women with one to three positive lymph nodes in these
trials even when systemic therapy was given. For today's women, who in many countries
are at lower risk of recurrence, absolute gains might be smaller but proportional
gains might be larger because of more effective radiotherapy.
Funding
Cancer Research UK, British Heart Foundation, UK Medical Research Council.