Adjuvant Chemo Benefit Sustained in ER-Negative, Locally Recurrent Breast Cancer

Author(s):

The survival benefit with adjuvant chemotherapy in ER-negative breast cancer patients with isolated locoregional recurrence was sustained in the final analysis of the phase III CALOR trial.

Stefan Aebi, MD

The survival benefit with adjuvant chemotherapy in ER-negative breast cancer patients with isolated locoregional recurrence (ILRR) was sustained in the final analysis of the phase III CALOR trial. Patients in the study with ER-positive disease did not derive a similar survival benefit.

At median follow-up of 9 years, there were 27 disease-free survival (DFS) events in ER-negative patients and 40 in ER-positive patients (HR, 0.29; 95% CI, 0.13-0.67). The 10-year DFS rate in patients with ER-negative disease favored those assigned to chemotherapy (70% vs 34%). Ten-year DFS was 50% for ER-positive patients assigned to chemotherapy compared with 59% for those who were not (HR, 1.07; 95% CI, 0.57-2.00).

Ten-year overall survival (OS) was 73% in patients with ER-negative ILRR treated with chemotherapy versus 53% without chemotherapy (HR, 0.48; 95% CI, 0.19-1.20). Among patients with ER-positive ILRR, 10-year OS was 76% for those treated with chemotherapy versus 66% without (HR, 0.70; 95% CI, 0.32-1.55).

Investigators reported that these findings support previously released results from the 5-year analysis.

“The statistically significant benefit of [chemotherapy] for the cohort of patients with ER-negative ILRR was sustained. The extended follow-up now available strengthens conclusions for the ER-positive ILRR cohort: no benefit of chemotherapy was observed for these patients,” corresponding author Stefan Aebi, MD, Lucerne Cantonal Hospital, and colleagues wrote. “The CALOR trial indicates that 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.”

Between August 2003 and January 2010, the open-label, randomized, multicenter, international CALOR trial enrolled 162 patients with completely excised ILRR after unilateral breast cancer. Eligible patients were randomly assigned to investigator’s choice of chemotherapy (a multidrug regimen lasting for at least 3 months was recommended) or no chemotherapy.

Patients were stratified by prior chemotherapy, hormone receptor (ER, PR) status of ILRR, and location of ILRR. Patients with ER- and/or PR-positive ILRR were to receive adjuvant endocrine therapy and, if recurrence occurred while receiving endocrine therapy, physicians were advised to change the treatment regimen.

The median time to recurrence from primary cancer to ILRR was 3.6 years for the ER-negative cohort compared with 6.8 years for the ER-positive cohort. Most patients (94%) with ER-positive ILRR received prior endocrine therapy compared with just 9% of patients with ER-positive primary cancers who were receiving such treatment at the time of the ILRR diagnosis.

Chemotherapy prolonged breast cancer—free interval (BCFI) in patients with ER-negative ILRR. At 10 years, 70% of those patients were breast cancer–free compared with 34% of patients who did not undergo chemotherapy (HR, 0.29; 95% CI, 0.13-0.67). There was no such benefit for patients with ER-positive ILRR (58% vs 62%; HR, 0.94; 95% CI, 0.47-1.85).

Interaction tests comparing the effect of chemotherapy for ER-positive ILRR versus ER-negative ILRR are P interaction = .013 for DFS, .034 for BCFI; and .53 for OS.

The improvement in DFS associated with chemotherapy remained significant in a multivariable proportional hazards model that included factors for ER status of ILRR, location of ILRR, previous chemotherapy use, and interval from primary surgery. The interaction between ER status and chemotherapy effect was statistically significant, confirming the efficacy of chemotherapy depending on ER expression of the ILRR. The multivariable analysis of BCFI gave similar results, again with a statistically significant interaction between ER status and efficacy of chemotherapy.

Wapnir IL, Price KN, Anderson SJ, et al. Efficacy of chemotherapy for ER-negative and ER-positive isolated locoregional recurrence of breast cancer: final analysis of the CALOR trial [published online February 14, 2018]. J Clin Oncol. doi: 10.1200/JCO.2017.76.5719.