Adjuvant Chemotherapy for Isolated Locoregional Recurrence of Breast Cancer Associated With Significantly Better Disease-Free and Overall Survival
Isolated locoregional recurrence of breast cancer is associated with high risk of distant metastasis and death. In the CALOR trial reported in The Lancet Oncology, Aebi et al found that adjuvant chemotherapy after complete resection improves disease-free survival in patients with isolated locoregional recurrence, especially in patients with estrogen receptor–negative recurrence. Chemotherapy also significantly improved overall survival.
Study Details
In this pragmatic, open-label, international trial, 162 patients with histologically proven and completely excised isolated locoregional recurrence after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins were randomly assigned between August 2003 and January 2010 to receive chemotherapy(n = 85) or no chemotherapy (n = 77).
Chemotherapy was selected by investigators, with at least four courses of multidrug treatment being recommended. Patients with estrogen receptor–positive recurrence received adjuvant endocrine therapy, radiation therapy was mandatory for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival.
The chemotherapy and no chemotherapy groups were generally balanced for age (median, 56 years in both), primary surgery (breast-conserving in 61% and 60%), prior chemotherapy (58% and 68%), time from primary surgery to recurrence surgery (median, 5.0 and 6.2 years), and postmenopausal status (76% and 82%). They were also well matched for location of recurrence (breast in 55% in both, mastectomy scar or chest wall in 33% and 32%, regional lymph nodes in 12% and 13%), estrogen receptor–positive recurrence (66% and 62%), estrogen receptor–positive primary tumor (58% and 61%), progesterone receptor–positive recurrence (52% and 45%), treatment for recurrence (radiation therapy in 36% and 38%, HER2-targeted therapy in 7% and 5%), estrogen receptor– or progesterone receptor–positive recurrence (68% and 68%), and endocrine therapy in receptor-positive recurrence (91% and 96%, including luteinizing hormone–releasing hormone or oophorectomy in 7% and 19%, tamoxifen in 26% and 29%, and aromatase inhibitors in 81% and 79%).
Chemotherapy was received by 94% of patients in the chemotherapy group and one patient (1%) in the no chemotherapy group. Chemotherapy in the chemotherapy group included monotherapy with a taxane in 19% and capecitabine in 11% and multidrug treatment with an anthracycline-based regimen in 45% and a taxane-based regimen in 15%.
Improved Disease-Free and Overall Survival
After median follow-up of 4.9 years, 5-year disease-free survival was 69% in the chemotherapy group vs 57% in the no chemotherapy group (hazard ratio [HR] = 0.59, P = .046). Among women with estrogen receptor–negative recurrence, 5-year disease-free survival was 67% vs 35% (HR = 0.32, 95% confidence interval [CI] = 0.14–0.73), whereas rates were 70% vs 69% (HR = 0.94, 95% CI = 0.47–1.89) in those with estrogen receptor–positive recurrence; the interaction between treatment and estrogen receptor expression was significant (P = 0.046 for interaction). Interaction of treatment with estrogen receptor status of the primary tumor was not significant (P = 0.43 for interaction).
Five-year overall survival was also significantly improved with chemotherapy (88% vs 76%, P = .024), with no significant interaction of treatment and estrogen receptor expression status of the recurrence (P = .99).
Serious adverse events occurred in 15% of the chemotherapy group. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection.
The investigators concluded, “Adjuvant chemotherapy should be recommended for patients with completely resected [isolated locoregional recurrence] of breast cancer, especially if the recurrence is estrogen-receptor negative.”
Stefan Aebi, MD, of Luzerner Kantonsspital, Switzerland, is the corresponding author for The Lancet Oncology article.
The study was funding by the U.S. Department of Health and Human Services, Swiss Group for Clinical Cancer Research, Frontier Science and Technology Research Foundation, Australian and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland, Grupo Español de Investigación en Cáncer de Mama, and the Dutch Breast Cancer Trialists’ Group. The study authors reported no potential conflicts of interest.
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