ADJUVANT SYSTEMIC THERAPY FOR WOMEN WITH NODE-POSITIVE BREAST-CANCER

Objective: To facilitate the choice of systemic adjuvant therapy for w omen with node-positive breast cancer. Evidence: Systematic review, us ing MEDLINE from 1976 and CANCERLIT from 1983 to December 1996. Nonsys tematic review continued through lune 1997. Recommendations: Chemother apy should be offered to all premenopausal women with stage II breast cancer. Acceptable treatments regimens are those using cyclophosphamid e, methotrexate and Ei-fluorouracil (CMF) or doxorubicin (Adriamycin) and cyclophosphamide (AC). Cyclophosphamide, epirubicin and 5-fluorour acil (CEF) may be shown in the future to result in better disease-free survival than CMF. Personal choice, quality of life and costs also in fluence this choice. Systemic adjuvant chemotherapy should begin as so on as possible after the surgical incision has healed. The recommended duration of therapy is at least 6 cycles (6 months) for CMF or CEF, a nd at least 3 cycles (2 to 3 months) for AC. The recommended CMF regim en consists of 14 days of oral cyclophosphamide with intravenous metho trexate and 5 fluorouracil (5-FU) on days 1 and 8. This is repeated ev ery 28 days for 6 cycles. Potential toxic effects should be fully disc ussed with patients. When possible, patients should receive the full s tandard dosage. No recommendations about high-dose chemotherapy can ye t be made. Ovarian ablation is effective in premenopausal women with e strogen receptor-positive tumours. However, chemotherapy has been bett er studied and is considered the intervention of choice. Ovarian ablat ion should be recommended to women who decline chemotherapy. In the fu ture, a small benefit may be shown for the combination of ovarian abla tion plus chemotherapy in women with node-positive, estrogen receptor- positive cancers. At present there is insufficient evidence for this t o be recommended. Tamoxifen should not be recommended as the sole trea tment for premenopausal women with node-positive tumours. Routine use of tamoxifen after chemotherapy in premenopausal women cannot yet be r ecommended. Before recommending hormonal therapy in premenopausal wome n, both the long-term side effects and its effects on recurrence must be considered. Postmenopausal women with stage II, estrogen receptor-p ositive cancer should be offered adjuvant tamoxifen. The recommended d uration of tamoxifen therapy is 5 years. No other hormonal interventio n 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 o r AC. There is no proof that tamoxifen adds any benefit to chemotherap y. Tamoxifen alone may be of value. Women with estrogen receptor-posit ive tumours may gain a small additional benefit from taking chemothera py in addition to tamoxifen. This is an option for a motivated, well-i nformed patient. Patients should be offered the opportunity to partici pate in clinical trials whenever possible. Validation: The authors' or iginal text was revised by a writing committee, primary and secondary reviewers, and by The Steering Committee on Clinical Practice Guidelin es for the Care and Treatment of Breast Cancer. The final document ref lects a consensus of all these contributors.