Locoregional Management and Prognostic Factors in Breast Cancer With Ipsilateral Internal Mammary and Axillary Lymph Node Involvement

Purpose: Patients with breast cancer and ipsilateral axillary and internal mammary (IM) lymph node involvement (cN3b) often forgo IM node resection. Therefore, radiation is important for curative therapy. However, prognosis is not well described in the era of modern systemic therapy, and limited data exist to guide optimal locoregional treatment recommendations.

Methods and materials: We retrospectively reviewed 117 patients with nonmetastatic cN3b breast cancer treated at our institution between 2014 and 2019. Staging included ultrasound evaluation of all regional nodal basins. All patients received neoadjuvant chemotherapy, resection of the breast primary, and axillary nodal dissection, followed by adjuvant radiation to the breast/chest wall and regional nodes. Institutional guidelines recommend a 10-Gy boost to radiographically resolved nodes, and a 16-Gy boost to unresolved nodes. Overall survival, recurrence-free survival (RFS), locoregional RFS, internal mammary RFS, and distant metastasis-free survival were evaluated with Kaplan-Meier analysis. A multivariable model for RFS was constructed.

Results: Median follow-up for 117 patients was 3.82 years. Median age at diagnosis was 46 years and 56 patients (48%) were receptor group ER+/HER2-. Mastectomy was performed in 96 patients (82%), 38 (32%) had biopsy-confirmed IMC involvement, and 8 (7%) had IM node dissection. The median initial radiation dose was 50 Gy (range, 50-55 Gy) and IMC boost 10 Gy (range, 0-16 Gy). The 5-year overall survival, IM RFS, locoregional RFS, distant metastasis-free survival, and RFS were 74%, 98%, 89%, 68%, and 67%, respectively. On multivariable analysis, a clinical complete response of the IM nodes or ypN0 (pathologic complete response of nodes) status had improved 5-year RFS with hazard ratios of 0.24 (P = .006) and 0.27 (P = .05), respectively. Extranodal extension or lymphovascular invasion were associated with worse 5-year RFS with hazard ratios of 4.13 (P = .001) and 2.25 (P = .04), respectively.

Conclusions: Multimodality therapy provides excellent locoregional control of 89% at 5 years for patients with cN3b breast cancer. Adjuvant radiation yields a 5-year IM RFS of 98%. Clinical and pathologic response of IM nodes are independently prognostic for RFS.