The long-term outcomes seen by French researchers confirm studies showing that women with estrogen receptor-positive breast cancer have increased disease-free survival if they receive chemotherapy along with tamoxifen rather than tamoxifen alone.
As reported at the San Antonio Breast Cancer Symposium, disease-free survival after nine years was achieved by 83.5% of women who received standard chemotherapy plus tamoxifen compared with 72.2% of patients receiving tamoxifen monotherapy.
“In good-prognosis node-positive, postmenopausal patients, the fluorouracil, epirubicin, cyclophosphamide tamoxifen combination [FEC 50-TAM] significantly improved disease-free survival,” reported Moise Namer, MD, of Centre Antoine Lacassagne in Nice, France, presenting the results on behalf of the French Adjuvant Study Group (FASG).
“The results reported by the FASG confirm previous studies such as those performed by the Southwest Oncology Group and the National Surgical Adjuvant Breast and Bowel Project,” said Clifford Hudis, MD, Chief of the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center.
“The combination of anthracycline chemotherapy and tamoxifen appears to benefit women with node-positive, estrogen-receptor-positive breast cancer.”
Dr. Namer reviewed two studies performed by the collaborative group—the FASG-02 study undertaken between 1986 and 1990, and the FASG-07 study conducted between 1991 and 1998.
In the first trial 776 node-positive postmenopausal women were enrolled, but their hormone status was not determined; the second trial had 335 postmenopausal women with one to three positive nodes who were hormone-receptor positive.
“In both trials, we found an advantage of chemoendocrine therapy over tamoxifen alone,” Dr. Namer said.
“However, at the present time, it remains unclear if chemotherapy combined with tamoxifen improves disease-free survival in hormone-positive postmenopausal women. Thus we pooled both trials in order to evaluate the contribution of chemotherapy in those patients.”
The results, he said, clearly showed the benefit of adding chemotherapy to the regimen in preventing relapse. Relapse occurred in 16% of the patients on the combination therapy compared with 26% of the women receiving tamoxifen alone. Local relapse occurred in 2.2% of patients receiving both chemotherapy and tamoxifen compared with 6% of women receiving tamoxifen alone.
Trend to Better Survival
In overall survival, the multivariate analysis found that 85.5% of patients taking the combination survived for nine years compared with 77.5% of patients receiving tamoxifen alone. Although that result did not reach statistical significance, it did show a strong trend in favor of the combination treatment, Dr. Namer said.
In the multivariate analysis, aside from the treatment regimen, the only other significant determinant of disease-free survival was the original tumor size. Women who were treated with tumors smaller than 2 cm appeared to fare better than women with larger cancers.
Age, type of surgery—mastectomy or tumorectomy—cancer grade, or hormone-receptor status did not appear to have significant impact on outcome.
In both trials, the combination regimen included fluorouracil at 500 mg/m2 on the first day of treatment alone with epirubicin at 50 mg/m2 and cyclophosphamide at 500 mg/m2 in six cycles, 21 days apart, and tamoxifen at 30 mg/day for three years. The patients receiving tamoxifen only received it at a dose of 30 mg/day for three years.
The average age of the patients in both studies was 59 years, ranging from 44 to 69. More than 80% of women underwent mastectomies; about 85% of the cancers were ductal carcinomas.
A second cancer was observed in 7.2% of patients receiving the combination therapy compared with 4.5% of patients receiving tamoxifen. The difference did not reach statistical significance (p=0.13). Seven endometrial cancers occurred in the combination group; 5 occurred in patients taking tamoxifen only.
In the pooled analysis, Dr. Namer was able to identify 224 patients on the combination treatment and 233 patients on tamoxifen who were classified as having a good prognosis, meaning they had between one and three positive lymph nodes. All the women underwent surgery to remove the primary tumor.