Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional Recurrence of Breast Cancer: Final Analysis of the CALOR Trial

Abstract

Purpose Isolated locoregional recurrence (ILRR) predicts a high risk of developing breast cancer distant metastases and death. The Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial investigated the effectiveness of chemotherapy (CT) after local therapy for ILRR. A report at 5 years of median follow-up showed significant benefit of CT for estrogen receptor (ER)-negative ILRR, but additional follow-up was required in ER-positive ILRR. Patients and Methods CALOR was an open-label, randomized trial for patients with completely excised ILRR after unilateral breast cancer. Eligible patients were randomly assigned to receive CT or no CT and stratified by prior CT, hormone receptor status, and location of ILRR. Patients with hormone receptor-positive ILRR received adjuvant endocrine therapy. Radiation therapy was mandated for patients with microscopically involved margins, and anti-human epidermal growth factor receptor 2 therapy was optional. End points were disease-free survival (DFS), overall survival, and breast cancer-free interval. Results From August 2003 to January 2010, 162 patients were enrolled: 58 with ER-negative and 104 with ER-positive ILRR. At 9 years of median follow-up, 27 DFS events were observed in the ER-negative group and 40 in the ER-positive group. The hazard ratios (HR) of a DFS event were 0.29 (95% CI, 0.13 to 0.67; 10-year DFS, 70% v 34%, CT v no CT, respectively) in patients with ER-negative ILRR and 1.07 (95% CI, 0.57 to 2.00; 10-year DFS, 50% v 59%, respectively) in patients with ER-positive ILRR ( Pinteraction = .013). HRs were 0.29 (95% CI, 0.13 to 0.67) and 0.94 (95% CI, 0.47 to 1.85), respectively, for breast cancer-free interval ( Pinteraction = .034) and 0.48 (95% CI, 0.19 to 1.20) and 0.70 (95% CI, 0.32 to 1.55), respectively, for overall survival ( Pinteraction = .53). Results for the three end points were consistent in multivariable analyses adjusting for location of ILRR, prior CT, and interval from primary surgery. Conclusion The final analysis of CALOR confirms that CT benefits patients with resected ER-negative ILRR and does not support the use of CT for ER-positive ILRR.

Trial registration: ClinicalTrials.gov NCT00074152.

Figures

Fig 1.

CONSORT diagram of Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial update according to estrogen receptor (ER) status of the ILRR. CT, chemotherapy; ILRR, isolated locoregional recurrence; LFU, lost to follow-up; no CT, no chemotherapy.

Fig 2.

Disease-free survival (DFS), breast cancer–free interval (BCFI), and overall survival (OS) for patients with (A-C) estrogen-receptor (ER)-negative and (D-F) ER-positive isolated locoregional recurrence (ILRR). Interaction tests comparing the effect of chemotherapy (CT) for patients with ER-negative ILRR versus ER-positive ILRR are Pinteraction = .013 for DFS (A v D); Pinteraction = .034 for BCFI (B v E); and Pinteraction = .53 for OS (C v F). No CT, not assigned to chemotherapy; HR, hazard ratio.

Fig 3.

Subgroup analysis of disease-free survival according to estrogen-receptor (ER) status of isolated locoregional recurrence (ILRR) and ER status of primary breast cancer tissue among 143 patients with known primary ER status. The size of the boxes is proportional to the number of events. The x-axis is on a log scale. CT, assigned to chemotherapy; no CT, not assigned to chemotherapy. (*) 143 of the 162 randomly assigned patients.