Late effects of adjuvant oophorectomy and chemotherapy upon premenopausal breast cancer patients

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Abstract
Between 1978 and 1981 we conducted a trial (Trial II) in premenopausal and perimenopausal breast cancer patients with 4 or more metastatic axillary lymph nodes. 327 evaluable patients were randomized after at least a total mastectomy and axillary clearance to receive either a combination chemotherapy with cyclophosphamide, methotrexate, 5-fluorouracil, and low-dose prednisone (CMFp), or surgical oophorectomy followed by the same CMFp therapy (Ox + CMFp). Cytotoxic drugs were administered for 12 4 week courses. At a median follow-up of 96 months, the 8-year disease-free survival (DFS) percentages (± s.e.) for CMFp and Ox+ CMFp were 30%±4% and 37%± 4%, respectively (p = 0.17). The overall survival percentages were 41% ±4% and 50% ±4%, respectively (p = 0.20). In a subgroup analysis by estrogen receptor content of the primary, the differences were observed in patients with tumors classified as ER+ (8-year DFS: 26%±7% 41% ± 7% p = 0.09) but not in those with ER- tumors (8-year DFS: 29%±7%, 25%±7%; p = 0.92). Analysis of sites of first relapse showed that the difference between the two treatment groups can be entirely attributed to the reduction in bone metastases in the oophorectomized group (Ox + CMFp). We conclude that for very high risk premenopausal breast cancer patients, the effects of oophorectomy added to an adjuvant cytotoxic regimen will be observed late in the patients' follow-up period. We hypothesize that the reduction of relapses in distant sites is due to the extended effects of the endocrine therapy.