Commentary on MA.20 trial

Background: Randomized trials of regional lymph node treatment in early stage breast cancer have been mostly negative for any improvements in survival. This includes phase III studies of axillary dissection, internal mammary node dissection, or radiation. However, studies of regional node irradiation have in some cases been associated with improved survival in the setting of postmastectomy radiation. The NCIC MA20 was designed to test the benefit of regional node irradiation in the setting of breast conserving surgery.

Study Methods: Eligibility for this trial included node-positive women, or node-negative women with high risk features: tumors over 5 cm, or tumors over 2 cm with poor prognostic factors. Patients were randomized to receive whole breast radiation with or without comprehensive regional node irradiation (internal mammary, supraclavicular, and axillary nodes). Adjuvant chemotherapy and endocrine therapy was given according to institutional preference and trastuzumab when available in later years of the study. The trial was designed to detect a 5% improvement in overall survival for patients treated with regional nodal irradiation at 5 years from 80% to 85%.

Results: 1,832 patients were enrolled from 2000-2007. There was no difference in overall survival or breast cancer mortality. The study result was at 10 years an overall survival of 82.8% with nodal irradiation and 81.8% without (p=0.38). There was an improved disease-free survival with regional node irradiation (82% vs. 77%, respectively, p=0.01). There was a trend towards improved survival in the subgroup of patients with ER negative breast cancer treated with regional node irradiation. There was a modest improvement in local-regional recurrence with radiation to the regional nodes (95.2% vs. 92.2%, respectively, p=0.009). There were higher rates of grade 2 or higher pneumonitis and lymphedema with regional node irradiation.

Conclusion: Although there was no improvement in overall survival, the reduction in breast cancer recurrence will make the use of regional node irradiation a consideration for some patients with node-positive breast cancer. The modest potential benefit needs to be weighed against the increased risk for toxicity in joint decision making with the patient. The study does not resolve controversies in the radiation oncology community over which regional nodal groups are essential for treatment (i.e. – internal mammary versus supraclavicular and infraclavicular nodes alone). In the past, radiation oncologists have used gross tumor features such as inner quadrant and node positive for patient selection for regional node irradiation; however, the present study with its finding of a greater benefit in ER-negative patients and offers promise that future patient selection could be based more on molecular characterization of high risk instead.