Survival advantage of adjuvant chemotherapy in high-risk node-negative breast cancer: ten-year analysis--an intergroup study.

PURPOSE: Preliminary analysis showed that adjuvant chemotherapy is effective in improving disease-free survival (DFS) among high-risk breast cancer patients. This report updates the analysis of the high-risk group and reports the results of the low-risk group. METHODS: Patients who had undergone a modified radical mastectomy or a total mastectomy with low-axillary sampling, with negative axillary nodes and either an estrogen receptor-negative (ER-) tumor of any size or an estrogen receptor-positive (ER+) tumor that measured > or = 3 cm (high-risk) were randomized to receive six cycles of cyclophosphamide, methotrexate, fluorouracil, and prednisone (CMFP) or no further treatment. Patients with ER+ tumors less than 3 cm (low-risk) were monitored without therapy. RESULTS: DFS and overall survival (OS) at 10 years were 73% and 81%, respectively, among patients who received chemotherapy, as compared with 58% and 71% in the observation group (P=.0006 for DFS and P=.02 for OS). Chemotherapy was beneficial for patients with large tumors, both ER+ and ER-, showing a 10-year DFS of 70% versus 51 % (P=.0009) and OS of 75% versus 65% (P=.06). Ten-year survival was 77% among low-risk patients, 85% among premenopausal patients, and 73% in the postmenopausal group. CONCLUSION: The observed 37% reduction in risk of recurrence and 34% reduction in mortality risk at 10 years, associated with a 15.4% absolute benefit in disease-free state and 10.1% in survival, reaffirm the role of adjuvant chemohormonal therapy in the management of high-risk node-negative breast cancer. Tumor size remains a significant prognostic factor associated with recurrence and survival in the low-risk group.

Chemotherapy versus observation in high-risk node-negative breast cancer patients.

Postoperative women with breast cancer but without histopathological evidence of metastases to the axillary lymph nodes or clinical evidence of metastases were studied. Six hundred fifty-five "good-risk" patients who were estrogen receptor positive (ER+) with primary tumors less than 3 cm were registered for observation. Twenty-four of these patients were treated with chemotherapy. Five hundred thirty-six "poor-risk" patients who were either ER+ with primary tumors greater than or equal to 3 cm or estrogen receptor negative (ER-) with any primary tumor size were randomly assigned between chemotherapy and observation. Randomization was stratified by type of surgical procedure, number of lymph nodes examined, menopausal status, tumor size, and ER status. The chemotherapy (CMFP) consisted of six 4-week cycles of cyclophosphamide, 100 mg/m2 orally days 1-14; methotrexate, 40 mg/m2 intravenously (IV) days 1 and 8; fluorouracil, 600 mg/m2 IV days 1 and 8; and prednisone, 40 mg/m2 orally days 1-14. Treatment arms in the randomly assigned patients were balanced with respect to pretreatment characteristics. This analysis includes 445 eligible patients entered in the registration arm and 425 eligible patients entered into the randomized treatments. The median follow-up is 4.5 years in the randomly assigned cohort and 4.8 years in the registered cohort. The overall 5-year disease-free survival (DFS) among the randomly assigned patients was 83% with CMFP and 61% with observation (P less than .0001). A DFS treatment benefit was observed in premenopausal and postmenopausal patients as well as in patients with ER+ or ER- tumors. There were fewer local-regional and distant relapses among the CMFP-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis and management of colovesical fistulas.

Diagnosis and management may present difficult problems in patients with colovesical fistulas. Symptoms in the urinary tract are most common, and cystoscopy, and cystography are the most valuable diagnostic procedures. It may not always be possible to demonstrate the fistula by diagnostic tests, and a high index of suspicion should be maintained in patients with inflammatory or neoplastic disease of the rectosigmoid area or bladder with recurrent cystitis. Definitive treatment should include resection of the fistula and diseased segment of the intestine. Both one stage and multistage procedures have their place in the treatment of this condition. There are specific criteria for success for a one stage procedure.

Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer. An intergroup study.

We randomly assigned 536 women who had undergone either a modified radical mastectomy or a total mastectomy with low axillary-node dissection for potentially curable breast carcinoma to receive adjuvant chemotherapy or no-treatment observation. The patients were considered at high risk for recurrence because they had either an estrogen-receptor-negative tumor of any size or an estrogen-receptor-positive tumor at least 3 cm in diameter with no histopathological evidence of axillary-node involvement. The chemotherapy consisted of six four-week cycles of cyclophosphamide (100 mg per square meter of body-surface area orally on days 1 through 14), methotrexate (40 mg per square meter intravenously on days 1 and 8), fluorouracil (600 mg per square meter intravenously on days 1 and 8), and prednisone (40 mg per square meter orally on days 1 through 14). Treatments were balanced with respect to patients' characteristics. The analysis included 406 eligible patients who were entered in the study before October 1, 1987. The overall disease-free survival among patients treated with the four-drug regimen was 84 percent, as compared with 69 percent for the control group, at a median follow-up of three years (P = 0.0001). A treatment benefit was also observed in premenopausal and postmenopausal patients as well as in patients with estrogen-receptor-positive or with estrogen-receptor-negative tumors. Severe or life-threatening hematologic toxicity was encountered in 33 percent of the treated patients, with one death. Our results indicate that adjuvant chemotherapy with six cycles of cyclophosphamide, methotrexate, fluorouracil, and prednisone is effective in improving three-year disease-free survival among high-risk patients with axillary-node-negative, operable breast cancer. An analysis of the effect of treatment on survival awaits a longer follow-up.