Adjuvant systemic therapy for women with node-positive breast cancer. The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer.

OBJECTIVE: To facilitate the choice of systemic adjuvant therapy for women with node-positive breast cancer. EVIDENCE: Systematic review, using MEDLINE from 1976 and CANCERLIT from 1983 to December 1996. Nonsystematic review continued through June 1997. RECOMMENDATIONS: Chemotherapy should be offered to all premenopausal women with stage II breast cancer. Acceptable treatments regimens are those using cyclophosphamide, methotrexate and 5-fluorouracil (CMF) or doxorubicin (Adriamycin) and cyclophosphamide (AC). Cyclophosphamide, epirubicin and 5-fluorouracil (CEF) may be shown in the future to result in better disease-free survival than CMF. Personal choice, quality of life and costs also influence this choice. Systemic adjuvant chemotherapy should begin as soon as possible after the surgical incision has healed. The recommended duration of therapy is at least 6 cycles (6 months) for CMF or CEF, and at least 4 cycles (2 to 3 months) for AC. The recommended CMF regimen consists of 14 days of oral cyclophosphamide with intravenous methotrexate and 5 fluorouracil (5-FU) on days 1 and 8. This is repeated every 28 days for 6 cycles. Potential toxic effects should be fully discussed with patients. When possible, patients should receive the full standard dosage. No recommendations about high-dose chemotherapy can yet be made. Ovarian ablation is effective in premenopausal women with estrogen receptor-positive tumours. However, chemotherapy has been better studied and is considered the intervention of choice. Ovarian ablation should be recommended to women who decline chemotherapy. In the future, a small benefit may be shown for the combination of ovarian ablation plus chemotherapy in women with node-positive, estrogen receptor-positive cancers. At present there is insufficient evidence for this to be recommended. Tamoxifen should not be recommended as the sole treatment for premenopausal women with node-positive tumours. Routine use of tamoxifen after chemotherapy in premenopausal women cannot yet be recommended. Before recommending hormonal therapy in premenopausal women, both the long-term side effects and its effects on recurrence must be considered. Postmenopausal women with stage II, estrogen receptor-positive cancer should be offered adjuvant tamoxifen. The recommended duration of tamoxifen therapy is 5 years. No other hormonal intervention apart from tamoxifen can be recommended for postmenopausal patients. Women with estrogen receptor-negative tumours who are fit to receive chemotherapy (generally younger than 70 years) should be offered CMF or AC. There is no proof that tamoxifen adds any benefit to chemotherapy. Tamoxifen alone may be of value. Women with estrogen receptor-positive tumours may gain a small additional benefit from taking chemotherapy in addition to tamoxifen. This is an option for a motivated, well-informed patient. Patients should be offered the opportunity to participate in clinical trials whenever possible. VALIDATION: The author's original text was revised by a writing committee, primary and secondary reviewers, and by the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. The final document reflects a substantial consensus of all these contributors.