Outcome following local-regional recurrence in women with early-stage breast cancer: impact of biologic subtype.

ABSTRACT

Local-regional recurrence (LRR) after breast-conserving therapy (BCT) can result in distant metastasis and decreased disease-free survival (DFS). This study examines factors associated with DFS following LRR. The initial population included 2,233 consecutive women who underwent BCT from 1998 to 2007. Biologic subtype was approximated using a combination of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. Cumulative incidence of DFS after LRR was calculated. The association of clinical, pathologic, and treatment parameters with DFS was evaluated using a Cox regression model. At a median follow-up of 105 months, 82 patients (3.7%) had a LRR. Of these, 66 (80%) were in-breast and 16 (20%) involved the ipsilateral lymph nodes. Twenty patients subsequently developed distant metastases. Five-year DFS after initial recurrence was 69.6% for the overall cohort. On univariate analysis, triple-negative disease (ER/PR/HER2 negative, TNBC) was associated with reduced DFS (HR = 3.8; 95% CI 1.8-8.1; p < 0.001). Other factors associated with reduced DFS were larger tumor size (HR = 1.3; 95% CI 1.03-1.6; p = 0.02), shorter interval from initial diagnosis to LRR (HR = 0.98 per month; 95% CI 0.97-0.99; p = 0.02), and no salvage surgery (HR = 0.2; 95% CI 0.09-0.5; p = 0.001). On multivariate analysis, TNBC remained the most significant factor associated with reduced DFS (HR = 4.8; 95% CI 2.25-10.4; p < 0.001). Compared to women with luminal A disease, those with TNBC had significantly worse DFS (37.5% versus 88.3% at 5 years; p < 0.001). Women with TNBC who developed LRR were at high risk of subsequent recurrence. Efforts should be targeted toward both preventing initial recurrence and decreasing subsequent metastasis.