Prognostic Factors in Breast Cancer Patients With Clinical N3b (Ipsilateral Internal Mammary and Axillary) Disease

Abstract

<h3>Purpose/Objective(s)</h3> Patients with clinical N3b (cN3b) breast cancer often do not undergo surgical resection of gross internal mammary (IM) nodes. Therefore, radiation is important for curative therapy. However, limited data exist to guide treatment recommendations. <h3>Materials/Methods</h3> We retrospectively reviewed 119 patients with non-metastatic cN3b breast cancer treated at our institution between 2014 and 2019 with curative intent. Staging included u/s evaluation of all regional nodal basins. All patients received neoadjuvant chemotherapy (NAC), surgical resection of the breast primary and nodal dissection, followed by adjuvant radiation to the chest wall/breast, infraclavicular (ICV), SCV and IM nodes. Institutional nodal boost guidelines recommend 10 Gy to radiographically resolved N3b nodal basins, and 16 Gy to unresolved N3b nodes, normal tissue constraints permitting. Patient, tumor, and treatment characteristics were collected and analyzed using a saturated multivariable analysis (MVA) model with backwards elimination to identify variables associated with improved overall survival (OS) at <i>P</i> < 0.10. Local (LC), regional control (RC), freedom from distant metastases (FFDM), and overall survival (OS) were evaluated with Kaplan Meier analysis. <h3>Results</h3> 119 patients were analyzed with a median follow-up of 2.78 years. Median age at diagnosis was 46 years, 56 (47%) were ER+/HER2-, 19 (16%) ER+/HER2+, 13 (11%) ER- /HER2+, and 31 (26%) ER-/HER2-, 86 (74%) had high grade histology, and 68 (57%) had cT3/T4 disease. Mastectomy was performed in 96 (81%) of patients, 36 (30%) had biopsy confirmed IMC involvement, and 8 (7%) had dissection of IM nodes. The median initial radiation dose was 50 Gy (range, 50-55), IMC boost 10 Gy (range, 8-16), and 41 (34%) received cumulative IMC dose > 60 Gy. The 3-year OS, FFDM, RC, and LC were 80%, 71%, 93%, and 94%, respectively. Patients with a nodal pCR of dissected nodes, had improved 3-year OS, 95% vs 71% (<i>P</i> = 0.008). Among patients who had a nodal pCR, nodal boost to > 60 Gy did not significantly improve 3-year OS, 100% vs. 93% (<i>P</i> = 0.40). In patients with less than a nodal pCR, who received IMC > 60 Gy, 3-year OS was numerically improved but was not statistically significant 81% vs. 64% (<i>P</i> = 0.33). In MVA, cumulative IMC dose > 60 Gy, nodal pCR, ER positivity, HER2 positivity, and lower clinical T-stage were independently associated with improved OS (Table 1). <h3>Conclusion</h3> Nodal pathologic response to NAC and cumulative IMC dose > 60 Gy were independently predictive for improved OS in patients with non-metastatic cN3b breast cancer treated with curative intent. Regional nodal control using a boost was excellent even among those with less than nodal pCR.