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

Abstract

Neoadjuvant chemotherapy (NAC) is standard of care for locally-advanced breast cancer and is increasingly used for early-stage high-risk disease. Previous studies have shown wide variation in radiation (RT) practice and limited data on locoregional relapse (LRR) following NAC. We hypothesized a low LRR risk after treatment 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. Data from 416 stage II/III breast cancer patients treated with NAC, surgery, and adjuvant RT at our institution between 2008 and 2015 were retrospectively reviewed. Hormone receptor (HR) and HER2 status defined molecular subtypes: HR+HER2- (45%), HR-HER2+ (11%), HR+HER2+ (22%), and HR-HER2- (22%). DFS and OS rates were calculated using the Kaplan-Meier method. LRR rate was estimated using the cumulative incidence function, treating death as a competing risk. Multivariable survival analysis was performed using Cox regression. Median follow-up was 4.7 years (range 0.5 – 10.7). Median age was 48 years (range 24 - 79). Most patients had cT2/3 (75%) cN1 (62%) disease and underwent mastectomy (76%) and axillary dissection (84%). pCR was achieved in 23% of patients: 8% of HR+HER2-, 53% of HR-HER2+, 19% of HR+HER2+, and 41% of HR-HER2- subtype. All patients received adjuvant RT, most (99%) with 50 Gy in 25 fractions. Nodal RT was given to 96% of the patients: 83% axilla and supraclavicular fossa (SCF); 8.5% SCF alone; 8% axilla, SCF, and internal mammary nodes (IMN); and 0.5% SCF and IMN. There were 19 local, 17 regional, and 88 distant failures (DM). Of the 27 patients with LRR (12 HR+HER2-, 0 HR-HER2+, 6 HR+HER2+, 9 HR-HER2-), all but 4 developed DM, 13 of which were synchronous. Two developed LRR 2 months after surgery, prior to adjuvant RT. LRR could be mapped in 22 patients: most (19) recurred in the RT field (in-field); 1 in- and out-of-field; and 2 out-of-fields (1 isolated IMN recurrence and 1 IMN with DM). The 5-year LRR, DFS, and OS were 6.4%, 77%, and 90% for the entire cohort, respectively. On multivariable analysis, HR-HER2- subtype, stage III disease, and non-pCR were associated with poor DFS and OS (Table 1). Breast cancer patients treated with NAC, surgery, and RT have low 5-year LRR risk. Most LRR occur in-field. HR-HER2- subtype, stage III disease, and non-pCR are associated with poor DFS and OS.Abstract 2054; Table 1Multivariable Cox regression analysisCovariateDFSOSHR (95% CI)pHR (95% CI)pMolecular SubtypeHR+HER2-ReferenceReferenceHR-HER2+0.52 (0.2, 1.34)0.181.21 (0.39, 3.79)0.75HR+HER2+0.58 (0.32, 1.04)0.070.73 (0.28, 1.89)0.52HR-HER2-2.19 (1.33, 3.61)0.0023.91 (1.92, 7.95)<0.001StageIIReferenceReferenceIII1.78 (1.14, 2.79)0.011.74 (0.91, 3.35)0.095pCR0.24 (0.11, 0.53)0.0010.38 (0.15, 0.96)0.04 Open table in a new tab