Adjuvant therapy for node-negative breast cancer. The use of prognostic factors in selecting patients. Patients with invasive breast cancer and pathologically negative lymph nodes (NO) have a favorable 10-year survival rate, particularly with small (less than 1 cm) primary tumors. Overall, however, 20% to 35% will experience recurrence with local therapy only. Adjuvant chemotherapy or tamoxifen have prolonged disease-free survival (DFS), but not overall survival (OS). Unanswered questions of optimal end point (DFS or OS) and the risk of treating many to benefit few have prompted clinicians to use prognostic indicators to facilitate treatment recommendations. Currently, the most readily available and accurate information comes from TNM staging, pathologic features, and hormone receptors. Ploidy, S-phase fraction, HER-2-neu amplification or over-expression, and cathepsin-D may be useful prognostic indices. Until a more precise system of weighing several prognostic variables is developed, the decision to recommend adjuvant systemic therapy in this generally good prognosis group will have to be thoughtfully considered by patient and physician. Whenever possible, patients should be encouraged to enter clinical trials. 