Clinical practice guidelines for the care and treatment of breast cancer : 8 . Adjuvant systemic therapy for women with node-positive breast cancer ( 2001 update )

Objective: To assist patients with node-negative breast cancer and their physicians in arriving at optimal decisions regarding treatment. Evidence: Based on systematic literature review using MEDLINE from 1980 and CANCERLIT from 1983 to July 2000. Nonsystematic review of literature was continued through November 2000. Recommendations: • Before deciding whether to use adjuvant systemic therapy, the prognosis without adjuvant therapy should be estimated. • A patient’s risk for recurrence can be categorized as low, intermediate or high on the basis of tumour size, histologic or nuclear grade, estrogen receptor (ER) status, and lymphatic and vascular invasion (LVI). • For each individual, the choice of adjuvant therapy must take into account the potential benefits and possible side effects. These must be fully explained to each patient. • Preand postmenopausal women who are at low risk of recurrence can be advised not to have adjuvant systemic treatment. Women who are at low risk, if seeking treatment, may consider tamoxifen. • Women at high risk should be advised to have adjuvant systemic therapy. Chemotherapy should be recommended for all premenopausal women (less than 50 years of age) and for postmenopausal women (50 years of age or older) with ER-negative tumours. Tamoxifen should be recommended as first choice for postmenopausal women with ER-positive tumours. For this last group of patients, further benefit is obtained from the addition of chemotherapy to tamoxifen, but the expected incremental toxicity must also be considered. Whether tamoxifen following chemotherapy should be routinely recommended for premenopausal women with ER-positive tumours is unclear. • For women at intermediate risk with ER-positive tumours, tamoxifen should normally be the first choice. For those who decline tamoxifen, chemotherapy may be considered. 2 • For most patients over 70 years of age who are at high risk, tamoxifen is recommended for ERpositive tumours. For those with ER-negative disease who are in robust good health, chemotherapy is a valid option. • There are 2 recommended chemotherapy regimens: (1) 6 cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF); (2) 4 cycles of Adriamycin and cyclophosphamide (AC). More intensive combinations such as CEF (cyclophosphamide, epirubicin and 5fluorouracil) and AC-Taxol have not yet been evaluated in node-negative disease. • Tamoxifen should normally be administered at a dose of 20 mg daily for 5 years. • Patients should be encouraged to participate in therapeutic trials whenever possible. Validation: The authors’ 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 consensus of all these contributors. External validation of the 1998 guidelines was through the CMAJ review process; the current update did not require external review. A writing committee updated the original guideline and then submitted it for further review, revision and approval by the Steering Committee. Sponsor: The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer was convened by Health Canada. Completion date: November 2000. _____________________________________________________________________________ The term “adjuvant systemic therapy” refers to all anticancer medications used after surgical treatment of patients with breast cancer. The 2 forms of adjuvant therapy considered here are chemotherapy (cytotoxic drugs) and hormonal therapy (usually the antiestrogen, tamoxifen). This guideline focuses on adjuvant systemic therapy for women in whom the axillary lymph nodes have been shown to be free of cancer (node-negative disease) (see guideline 4 on axillary dissection). Over half of all patients in whom breast cancer is diagnosed have node-negative disease. Most women who present with node-negative disease are cured by surgery alone. The use of adjuvant therapy in women in whom the cancer has spread to the axillary nodes (node-positive disease) is addressed in a separate guideline (guideline 8). The decision to use adjuvant systemic therapy is taken after weighing the benefits of reducing the risk of recurrence against the undesirable side effects and risks of the therapy in question. Since the value placed on different health effects is subjective, the process of weighing potential benefits against potential adverse effects must, to the extent that she wishes to do so, be carried out by the woman herself. To this end, the necessary information, including the uncertainty, must be carefully communicated to the patient in a way that enables her to make a truly informed decision. 3 This guideline reviews the evidence concerning the risks and benefits of adjuvant systemic therapy for node-negative breast cancer with the objective of assisting patients and their doctors in arriving at optimal treatment decisions. When making the decision of whether or not to administer adjuvant therapy, 3 questions must be considered: • What is the prognosis for this patient without adjuvant therapy? • To what extent will the prognosis be improved by the treatment? • What are the adverse effects of the treatment? ____________________________________________________________________