Natural history of node-negative breast cancer: are conventional prognostic factors predictors of time to relapse?

The purpose of this study was to determine a subpopulation of node-negative breast cancer patients at high risk of metastases and to analyse the relationship between conventional prognostic factors and the onset of metastatic disease. Patients with node-negative breast cancer, who were not receiving systemic adjuvant therapy, were prospectively enrolled into a multicentre study. We studied the onset of metastatic disease in relation to family history, age, and tumour characteristics of 2683 registered patients, 2213 were available for analysis. Median follow-up was 100 months. Metastatic disease-free survival was 88% at 5 years and 80% at 10 years. The two strongest prognostic factors in a multivariate analysis tumour Scraff, Bloom and Richardson (SBR) grade (P<0.0001) and size (P<0.02), were used to classify patients into three groups with different risks of relapse at 10 years: (1) lowest (8.4%) risk: SBR I and ≤1 cm; (2) intermediate (20%) risk: SBR I and >1 cm or SBR II or SBR III and ≤2 cm; (3) highest (32%) risk: SBR II or SBR III and >2 cm. A peak in the incidence of metastases was noted between 2 and 4 years, and a nadir between 6 and 8 years, after surgery. SBR grade is a highly predictive factor in node-negative breast cancer. The time course of the appearance of metastases is not linear. Prognostic factors are related to the height of an early peak in the occurrence of metastases rather than to the timing of this peak.