ER-Negative Isolated Locoregional Recurrence Benefits From Chemotherapy

A final analysis of the randomized CALOR trial found that patients with estrogen receptor (ER)-negative isolated locoregional recurrence (ILRR) after unilateral breast cancer derive significant benefit from chemotherapy, while those with ER-positive disease do not.

“After an ILRR event of breast cancer, the risk of distant metastases and death is high,” wrote study authors led by Stefan Aebi, MD, of Lucerne Cantonal Hospital in Switzerland. Previous reports from the CALOR trial found that after a median of 5 years, there was significant benefit with chemotherapy for ER-negative ILRR, but further follow-up was needed to determine its efficacy in ER-positive patients.

The new analysis extended the follow-up to a median of 9 years. In total, the trial included 162 patients, 58 of whom had ER-negative ILRR and 104 of whom had ER-positive ILRR. All patients had completely excised ILRR after unilateral breast cancer, and they were randomized to receive either chemotherapy (29 ER-negative patients, 56 ER-positive patients) or no chemotherapy (29 ER-negative patients, 48 ER-positive patients). The results of the analysis were published in the Journal of Clinical Oncology.

The 10-year disease-free survival (DFS) rate was 70% in ER-negative patients receiving chemotherapy, compared with 34% in those who did not receive chemotherapy, for a hazard ratio (HR) of 0.29 (95% CI, 0.13–0.67). In contrast, the 10-year DFS rate in ER-positive patients who received chemotherapy was 50%, compared with 59% in those who did not, for an HR of 1.07 (95% CI, 0.57–2.00).

Similar results were seen for breast cancer–free interval. Just as with DFS, 70% of ER-negative ILRR patients were breast cancer free at 10 years if they received chemotherapy; 34% were if they did not receive chemotherapy, for an HR of 0.29 (95% CI, 0.13–0.67). For ER-positive patients, 58% of patients treated with chemotherapy were breast cancer free at 10 years, compared with 62% of those who did not receive chemotherapy, for an HR of 0.94 (95% CI, 0.47–1.85).

For overall survival, ER-negative patients who received chemotherapy had a 10-year rate of 73%, compared with 53% without chemotherapy, for an HR of 0.48 (95% CI, 0.19–1.20). ER-positive patients who received chemotherapy had a 10-year rate of 76%, compared with 66% in those who did not receive chemotherapy, for an HR of 0.70 (95% CI, 0.32–1.55). Multivariate analyses yielded similar results for all three endpoints.

“This updated analysis demonstrates that patients with an ILRR should be managed according to the endocrine molecular profile of the recurrent cancer and not the primary cancer,” the authors wrote. “At present, chemotherapy offers the best prospect of prolonged DFS in patients with ER-negative first ILRR, whereas adding chemotherapy to endocrine therapy seems to offer no benefit to patients with ER-positive ILRR.”