Frequency of first metastatic events in breast cancer: Implications for sequencing of systemic and local-regional treatment

Purpose: The sequencing of treatment for early breast cancer is controversi al. The purpose of this study was to quantify the risk of delaying surgery, using estimates of the frequency of first metastases from breast primary t umors, Patients and Methods: The probability that 560 (node-negative), 657 (with o ne to three positive nodes), and 505 (with more than three positive nodes) women treated without adjuvant chemotherapy would be free of distant diseas e at presentation wets fit to a mathematical model of the seeding of distan t metastases and combined with estimates of the growth rate to calculate th e frequency of first distant disseminations per month. Results: Frequencies of first distant metastases were approximately 1% to 2 % per month, 2% to 4% per month, and 3% to 6% per month in T1 patients who were node-negative, had one to three positive nodes, or more than three pos itive nodes, respectively. As a resuit, the typical patient with T1 disease , who has ct 70% ta 80% chance of being free of distant disease, runs a 1% to 4% risk of distant dissemination for each month surgery is delayed. Assu ming a 30% reduction in mortality caused by adjuvant chemotherapy, the mode l predicts that T1 patients treated with neoadjuvant chemotherapy would pot entially have a higher rate of distant metastasis development than those tr eated with an initial surgical resection followed by adjuvant chemotherapy, Conclusion: We formulate the hypothesis that optimal sequencing of surgery and systemic treatment of breast cancer may be rite-dependent, with a disad vantage or no benefit from neoadjuvant treatment for T1 patients but an inc reasing benefit with increasing size of the primary tumor. (C) 1999 by Amer ican Society of Clinical Oncology.