Meta-analyses have shown that postmastectomy radiotherapy reduces risks of recurrence and breast cancer mortality in the population of all women with node-positive disease, but outcomes in those with only one to three positive nodes have not been specifically examined. As reported by Paul McGale, PhD, and colleagues in The Lancet, an individual patient data meta-analysis by the Early Breast Cancer Trialists’ Collaborative Group has shown that postmastectomy radiotherapy in this setting is associated with significantly reduced 10-year risk of recurrence and 20-year risk of breast cancer mortality.¹

Study Details

The meta-analysis included individual data for 8,135 women randomly assigned to treatment groups between 1964 and 1986 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery vs the same surgery without radiotherapy. Follow-up was 10 years for breast cancer recurrence and through January 1, 2009, for mortality.

The extent of axillary surgery was known for all but 183 women (2%). In total, 1,594 women (20%) had pathologically node-negative disease, 5,821 (72%) had pathologically node-positive disease, and pathologic nodal status was unknown for 720 (8%). A total of 3,831 women with known pathologic nodal status and known number of affected nodes had axillary dissection to at least level II and had zero, one to three, or at least four positive nodes. All of these patients were from trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain.

Node-Negative Disease

Of the 1,594 women with node-negative disease, 700 (44%) had axillary dissection, 870 (55%) had axillary sampling, and extent of axillary surgery was unknown for 24 (1%). Among the 700 with axillary dissection, radiotherapy vs no radiotherapy was associated with no significant differences in proportions of women who had a locoregional recurrence prior to a distant recurrence over 10 years (3.0% vs 1.6%, (2P > .1), 10-year overall recurrence (22.4% vs 21.1%, rate ratio [RR] = 1.06, 2P > .1), or 20-year breast cancer mortality (28.8% vs 26.6%, RR = 1.18, 2P > .1). However, radiotherapy was associated with significantly greater 20-year overall mortality (RR = 1.23, 2P = .03).

Among the 870 women with only axillary sampling [vs axillary dissection], radiotherapy was associated with reduced 10-year risk of locoregional recurrence (ie, locoregional recurrence before distant recurrence) (2P < .00001) and 10-year overall recurrence (RR = 0.61, 2P = .0003) but had no significant effect on 20-year breast cancer mortality (RR = 0.97, 2P > .1) or overall mortality (RR = 1.00, 2P > .1).

One to Three Positive Nodes

Of the 5,821 women with node-positive disease, 3,131 (54%) had axillary dissection, 2,541 (44%) had axillary sampling, and extent of axillary surgery was unknown for 149 (2%).

Among the 1,314 women with axillary dissection and one to three positive nodes, radiotherapy was associated with significant reductions in risk for 10-year locoregional recurrence (3.8% vs 20.3%, 2P < .00001), 10-year overall recurrence (34.2% vs 45.7%, RR = 0.68, 2P = .00006), and 20-year breast cancer mortality (42.3% vs 50.2%, RR = 0.80, 2P = .01).

A total of 1,133 of these women were in trials in which systemic therapy (cyclophosphamide, methotrexate, and fluorouracil, or tamoxifen) was given in both the radiotherapy and no-radiotherapy groups. Among these women, radiotherapy was associated with significantly reduced risk of locoregional recurrence (4.3% vs 21.0%, 2P < .00001), overall recurrence (33.8% vs 45.5%, RR = 0.67, 2P = .00009), and breast cancer mortality (41.5% vs 49.4%, RR = 0.78, 2P = .01).

Four or More Positive Nodes and All Node-Positive

Among the 1,772 women with axillary dissection and at least four positive nodes, radiotherapy was associated with significant reductions in 10-year risk for locoregional recurrence (13.0% vs 32.1%, 2P < .00001), 10-year overall recurrence (66.3% vs 75.1%, RR = 0.79, 2P = .0003), and 20-year breast cancer mortality (70.7% vs 80.0%, RR = 0.87, 2P = .04).

Among all 3,131 women with node-positive disease who had axillary dissection, radiotherapy was associated with significant reductions in risk for locoregional recurrence (8.1% vs 26.0%, 2P < .00001), overall recurrence (51.9% vs 62.5%, RR = 0.75, 2P < .00001), and breast cancer mortality (58.3% vs 66.4%, RR = 0.84, 2P < .001). In women not receiving radiotherapy, overall recurrence rates were higher during years 0 to 4 than during years 5 to 9.

There was little difference between radiotherapy and no-radiotherapy groups in breast cancer mortality during the first few years of follow-up, with a reduction among those receiving radiotherapy being observed thereafter through years 10 to 15 and possibly beyond. Radiotherapy also reduced 20-year overall mortality among all women with node-positive disease who had axillary dissection
(RR = 0.89, 2P = .01).

The investigators concluded:

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…. Radiotherapy techniques have improved in the past few decades and so the proportional benefits of radiotherapy are likely to be larger than in these trials. However, the absolute risks of breast cancer recurrence and mortality have reduced in many countries because of advances in detection and treatment of breast cancer, so the absolute benefits from postmastectomy radiotherapy today are likely to be smaller than those reported here. ■

Disclosure: The study was funded by Cancer Research UK, British Heart Foundation, and UK Medical Research Council. The study authors reported no potential conflicts of interest.

Reference

1. EBCTCG (Early Breast Cancer Trialists’ Collaborative Group): Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: Meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. March 19, 2014 (early release online).