Women with breast cancer who are undergoing breast-conserving surgery were assigned to receive whole-breast irradiation with or without regional nodal irradiation. At 10 years, disease-free survival in the nodal-irradiation group was improved but overall survival was not.
Many women with early-stage breast cancer undergo breast-conserving surgery followed by whole breast irradiation, which reduces the rate of local recurrence. Radiotherapy to the chest wall and regional lymph nodes, termed regional nodal irradiation, which is commonly used after mastectomy in women with node-positive breast cancer who are treated with adjuvant systemic therapy, reduces locoregional and distant recurrence and improves overall survival. An unanswered question is whether the addition of regional nodal irradiation to whole-breast irradiation after breast-conserving surgery has the same effect.
•Does the addition of regional nodal irradiation to whole-breast irradiation after breast-conserving surgery prolong survival in early-stage breast cancer?
In the study by Whelan et al., eligible patients were women with invasive carcinoma of the breast who were treated with breast-conserving surgery and sentinel-lymph-node biopsy or axillary-node dissection and who had positive axillary lymph nodes or negative axillary nodes with high-risk features. The study randomly assigned women to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). There was no significant between-group difference in overall survival, with 10-year rates of survival of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). Moreover, no significant difference was detected in breast-cancer mortality, with 10-year rates of 10.3% in the nodal-irradiation group and 12.3% in the control group (hazard ratio, 0.80; 95% CI, 0.61 to 1.05; P=0.11).
Figure 1. 10-Year Kaplan-Meier Estimates of Survival.
•Does the addition of regional nodal irradiation to whole-breast irradiation after breast-conserving surgery prolong disease-free survival in early-stage breast cancer?
In the Whelan study, the rate of disease-free survival was higher in the nodal-irradiation group than in the control group, with 10-year rates of 82.0% and 77.0%, respectively (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). The 10-year rates of isolated locoregional disease-free survival were 95.2% in the nodal-irradiation group and 92.2% in the control group (hazard ratio, 0.59; 95% CI, 0.39 to 0.88; P=0.009). The rates of distant disease-free survival at 10 years were 86.3% in the nodal-irradiation group and 82.4% in the control group (hazard ratio, 0.76; 95% CI, 0.60 to 0.97; P=0.03).
Table 2. Disease Recurrence or Death.
Morning Report Questions
Q: Are there increases in the rates of adverse events with the addition of regional nodal irradiation in early-stage breast cancer?
A: For acute events (those occurring 3 months or less after the completion of radiation), significant increases in the rates of radiation dermatitis and pneumonitis were reported in the nodal-irradiation group. For delayed events (those occurring 3 months or less after the completion of radiation), there were significant increases in the rates of lymphedema, telangiectasia of the skin, and subcutaneous fibrosis in the nodal-irradiation group. No increases in rates of brachial neuropathy, cardiac disease, or second cancers were observed in the nodal-irradiation group, but the period of follow-up was not sufficiently long to rule out a difference in the rate of secondary cancers.
Table 3. Adverse Events of Grade 2 or Higher.
Q: Were there any subgroups in the Whelan study that appeared to particularly benefit from the addition of regional nodal irradiation?
A: Although subgroup analyses were prespecified, they were generally not adequately powered to assess the benefit of treatment in different subgroups. Furthermore, the P values of the subgroup analyses were not adjusted for multiple testing. Patients with ER-negative or PR-negative tumors appeared to benefit more from regional nodal irradiation than those with ER-positive or PR-positive tumors. Although this effect was not observed in previous trials of postmastectomy radiation therapy, it supports the hypothesis that further research on the molecular characterization of the primary tumor may identify patients who are more likely to benefit from regional nodal irradiation. Since the number of node-negative patients in this trial was relatively small, the application of the study results to node-negative patients is unclear.