Prognostic impact of isolated tumor cells and micrometastases in axillary lymph nodes of breast cancer patients

With the introduction of the sentinel node (SN) procedure, the detection frequency of nodal isolated tumor cells and micrometastases has increased. We reviewed the literature on prognostic significance of these small nodal metastases. All studies before the SN era and all studies using the SN procedure that reported outcome in relation to presence of isolated tumor cells and/or micrometastases were included. Studies before the SN era were divided in 'cohort' and 'occult metastases' studies. The SN studies were divided in single-centre studies and in one multicentre cohort study. In the pre-SN cohort studies, axillary lymph node metastases of 2 mm or less were associated with reduced overall survival with an adjusted pooled hazard ratio of 1.44 (95%CI 1.29-1.62). In the pre-SN occult metastases studies, occult nodal metastases were associated with a pooled relative risk of deaths after 5 years of 1.45 (95%CI 1.11-1.88). In single-centre SN studies, using multivariate analyses, the presence of micrometastases was associated with a hazard ratio for disease events of 1.43 to 1.89 as compared to node-negative disease. The largest SN study, including nearly 2000 patients with isolated tumor cells or micrometastases, reported an adjusted hazard ratio for disease-events of 1.50 (95%CI 1.15-1.94) and 1.56 (95%CI 1.15-2.13), respectively, in patients who had not received systemic therapy. We conclude that isolated tumor cells and micrometastases are associated with increased risk of disease-events of about 1.5 compared to node-negative disease. Therefore, we recommend to consider the use of adjuvant systemic therapy in these patients.