RESUMEN
The effect of cyclophosphamide, methotrexate and fluorouracil (CMF) on ovarian function has been studied in 74 pre-menopausal patients with operable breast cancer. After median follow-up of 47 months, 50, 70 and 80% of 35 patients receiving CMF became permanently amenorrhoeic within 3, 6 and 12 months respectively; in contrast, only 5 in the no treatment (control) group of 39 patients became permanently amenorrhoeic within 12 months. Younger patients (less than 35 years) were more likely to retain or regain menstrual function while on or after CMF treatment. Estimation of ovarian and pituitary hormones in a subset of these women showed that CMF treatment was associated with a decrease in serum oestradiol and progesterone and an increase in serum follicle stimulating hormone and luteinizing hormone to post-menopausal levels. These hormonal changes are consistent with the induction of amenorrhoea during CMF treatment and the absence of resumption of menstrual function after completion of treatment suggests that CMF causes permanent ovarian ablation in a majority of these patients.
Asunto(s)
Amenorrea/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Factores de Edad , Neoplasias de la Mama/sangre , Neoplasias de la Mama/cirugía , Terapia Combinada , Ciclofosfamida/efectos adversos , Femenino , Fluorouracilo/efectos adversos , Hormonas/sangre , Humanos , Menopausia , Metotrexato/efectos adversos , Persona de Mediana EdadRESUMEN
The relation between tumour oestrogen and progesterone receptor status, menstrual status, relapse-free survival, and overall survival was analysed in 411 patients with early breast cancer randomised to receive either postoperative adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF) or no additional treatment (control). Prolongation of time to recurrence and survival was seen predominantly in premenopausal patients; these effects were seen only with tumours positive for steroid receptors, particularly progesterone. Chemotherapy led to permanent amenorrhoea in 61% of premenopausal patients. The therapeutic effects of chemotherapy were seen only when CMF induced permanent amenorrhoea in premenopausal patients. These findings support the hypothesis that the effect of adjuvant chemotherapy in early breast cancer may be mediated by ovarian suppression.