Functional form of the effect of the numbers of axillary nodes on survival in early breast cancer

Abstract

The change in survival in function of the numbers of involved and uninvolved axillary nodes in early breast cancer - i.e. the functional form - was investigated to search for prognostic cutoffs and to assess if ratio-based characterization of node involvement is a significant prognostic factor or not. Women aged 40-69, diagnosed in 1988-1997 with T1-T2 invasive breast carcinoma, who underwent axillary dissection, are selected from the SEER public database. The method determines the functional form by applying smoothed plots to the martingale residuals obtained from a proportional hazards model. The results on 55,267 selected patients find that the ratio of involved nodes on examined nodes, in a multivariate model that takes into account known prognostic factors (age, race, tumor size, topography, histology, grade, hormone receptors), is associated with a relative mortality hazard of 1.012 (95% confidence interval 1.010-1.014; relative increase of mortality of 1.2% for each 1% increase in the percentage of involved nodes). The functional form for the number of uninvolved nodes shows that the relative mortality hazard initially steeply decreases and then tends to level off beyond 5-10 uninvolved nodes. For the number of involved nodes, the relative mortality hazard continues to increase with each involved node without any obvious cutpoint. Even when the number of involved nodes is already large, each additional involved node increases the relative mortality hazard by at least 1.3%.