Pathology characteristics that optimize outcome prediction of a breast screening trial

The ability of pathology characteristics to predict outcome was tested with the 1029 cancers accumulated in the Edinburgh Randomized Trial of breast screening after 14 years follow-up. The majority (55.7%) were in the screening arm, which also had more operable cases (81.3% vs 62.2%); the reduction in the proportion of inoperable breast cancers in a UK female population invited to mammographic screening is a notable effect of the trial. In the 691 operable invasive cases the size, histological type, grade, node status and node number group individually showed highly significant (P<0.001) association with survival. In multivariate analysis the Nottingham Prognostic Index (NPI) derived from these features showed highly significant association with survival (P<0.001). However, when first adjusted for NPI, combined addition of pathological size in 6 categories and histological type as special or not had an independent association with survival that was statistically firmly based (P<0.001). For operable breast cancer the gains are in smaller sizes, better histological features, and higher proportion node negative. The weighting factors applied to pathology indicators of survival in the NPI are not optimal for a population included in a trial of screening. In particular, a linear trend of the index with pathological size is not appropriate. Inclusion of histological type as special or not improves the index further.