Patterns of Recurrence and Predictors of Survival in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy, Surgery, and Radiation

Abstract

Purpose: Neoadjuvant chemotherapy (NAC) is standard of care for locally advanced breast cancer. There is wide variation in radiation therapy (RT) practice and limited data describing locoregional relapse (LRR) after NAC. We hypothesized a low LRR risk with modern NAC, surgery, and RT and aimed to elucidate patterns of LRR and predictors of disease-free survival (DFS) and overall survival (OS) in these patients.

Methods and materials: Data from 416 patients with stage II/III breast cancer treated between 2008 and 2015 with NAC, surgery, and adjuvant RT were reviewed retrospectively. DFS and OS rates were calculated using the Kaplan-Meier method. The LRR rate was estimated using the cumulative incidence function, treating death as a competing risk. Multivariable survival analysis was performed using Cox regression.

Results: Median follow-up was 4.7 years. Most patients had cT2/3 (74%) cN1 (61%) disease and underwent mastectomy (75%) and axillary dissection (84%). Pathologic complete response (pCR) was achieved in 22% of patients. There were 27 LRRs (including 4 isolated LRRs) and 89 distant failures. Two patients developed LRR 2 months after surgery, before adjuvant RT. LRR could be mapped in 23 patients: most (20) recurred within the RT field; 1 in- and out-of-field; and 2 out-of-field. Five-year LRR, DFS, and OS were 6.4%, 77%, and 90%, respectively. On multivariable analysis, triple-negative subtype (hazard ratio [HR] 2.82; 95% confidence interval [CI], 1.78-4.47; P < .001), stage III disease (HR 1.72; 95% CI, 1.11-2.69; P = .016), and non-pCR (HR 4.76; 95% CI 2.13-10.0; P < .001) were associated with poor DFS and OS (HR 4.13 [95% CI, 2.21-7.72; P < .001]; HR 1.94 [95% CI, 1.001-3.75; P = .049]; and HR 2.38 [95% CI, 0.98-5.88; P = .055], respectively).

Conclusions: Patients with breast cancer treated with modern NAC, surgery, and RT have a low 5-year LRR risk, with the majority occurring in-field. Triple-negative subtype, stage III disease, and non-pCR were associated with inferior DFS and OS.