Patterns of relapse and metastatic spread in HER2-overexpressing breast cancer according to estrogen receptor status

Abstract

Purpose: The primary aim of this study was to compare the relapse patterns of estrogen receptor (ER)-positive and ER-negative patients with HER2-overexpressing breast cancer. A secondary aim was to distinguish the preferential primary site of metastases in HER2-overexpressing breast cancer.

Methods: Out of 886 patients treated for metastatic breast cancer (MBC) between January 1995 and December 2006, 269 patients with HER2-positive tumors were identified. Of these, 198 patients with relapsed breast cancer following surgery were included in this study. Rates and patterns of relapse and metastatic spread in HER2+/ER+ and HER2+/ER- patients were analyzed. This analysis was evaluated by the validation patients' cohort of our institute prospectively.

Results: Median relapse-free survival was longer in the HER2+/ER+ group than in the HER2+/ER- group (32.0 vs. 19.5 months, p = 0.0012). The peak of recurrence occurred at 12 months after surgery in the HER2+/ER- patients. The peak of relapse was later and the level was lower in the HER2+/ER+ patients (66 and 78 months following surgery) than in the HER2+/ER- patients (33 and 39 months following surgery, respectively). This result was reproduced by the validation cohort with great similarity. Young age [hazard ratio (HR) 1.59, p = 0.002], TNM stage 3 (HR 1.51, p = 0.005), and ER-negativity (HR 1.68, p < 0.0001) were identified as independent risk factors for relapse. Severe bone metastasis (HR 4.48, p = 0.028) and massive hepatic metastasis (HR 5.24, p = 0.043) were identified as independent risk factors for early relapse.

Conclusions: Our study shows that HER2-overexpressing breast cancer displays characteristic patterns of relapse and metastatic spread depending on ER status.