Regional Nodal Radiation Therapy and Breast Cancer Survival: Looking for Evidence

In the past, individual trials have examined the benefit of regional radiotherapy (RT) targeting lymph nodes for patients with breast cancer, but the trials varied as to whether RT was administered to the breast alone, chest wall, regional nodes, or some combination. The Early Breast Cancer Trialists' Collaborative Group (EBCTCG, also known as the Oxford Overview) has applied meta-analysis methodology to individual patient data from randomized trials worldwide to address the benefit of different treatment modalities relative to a common comparator. Now, EBCTCG has used this methodology to examine the clinical benefit of regional nodal RT to the internal mammary (IM) chain, supraclavicular (SC) fossa, and axillary nodes.

The EBCTCG's study covered 14,324 women in 16 trials beginning between 1961 and 2008. Over this period, significant improvements in RT techniques and planning allowed for more precise targeting and minimization of off-target toxicity. Early trials beginning before 1978 (2157 patients) used photon therapy, did not typically include chest-wall RT in patients with positive axillary nodes, and thus compared outcomes with regional nodal radiation versus no RT. The EBCTCG found no breast cancer survival benefit but greater non–breast cancer mortality associated with regional nodal RT.

In newer trials conducted since 1989, the RT was more tailored, and all patients received breast or chest-wall RT, with or without regional nodal RT. Most commonly, these trials compared no regional nodal RT with IM RT (5420 patients), IM and SC RT (4060 patients), or IM, SC, and axillary nodal RT (3716 patients). With a median follow-up of 14 patient-years, patients receiving regional nodal RT had significantly reduced risks for breast cancer recurrence and death and no excess of mortality from other causes. In absolute terms, the magnitude of 15-year mortality benefit from regional nodal RT increased as nodal involvement increased (benefit with node-negative illness, 1%–2%; ≥4 nodes, 4%–5%).