To prevent premature ovarian failure (POF), high-risk, premenopausal women with early breast cancer were given a luteinizing-hormone releasing hormone (LH-RH) analogue during adjuvant chemotherapy. After an adriamycin-based regimen, patients received radiation therapy concomitant with cyclophosphamide, methotrexate and 5-fluorouracil. An aromatase inhibitor was given to patients positive for the estrogen receptor (ER+). The median age was 43 years (range, 26-45). Among 200 consecutive patients, 46% had no axillary node, and 54% had a mean of 5.4 positive nodes (range, 1-25); 56% were ER+, 44% were estrogen receptor negative (ER-), 13% were triple negative, and 20 had tumors positive for the oncogene, c-erb-B2 (identified with fluorescent in situ hybridization). After a median follow-up of 105 months (range, 65-180), no patient under 40 years old exhibited POF, while 44% of patients over 40 years old exhibited POF. Eight pregnancies were recorded: 7 at term and 1 voluntary interruption. The 10-year disease-free survival and overall survival rates were 85 and 91%, respectively. These data showed that, in premenopausal patients with early breast cancer, the addition of an LH-RH analogue to adjuvant chemotherapy was well tolerated, prevented POF, and was associated with excellent disease-free survival and overall survival rates.