Genetic evolution of breast cancers III: Age-dependent variations in the correlations between biological indicators of prognosis

The influence of age on the occurrence of phenotypic features of prognostic significance was studied in relation to the DNA index values, measured on DNA histograms from a series of 1019 breast cancer patients. Globally, the distributions of all parameters showed variations with age, the most prominent being the decreases in the percentage of estrogen receptor-negative and high proliferative activity cases with increasing age. When analyzed according to the DNA index classes, all parameters were found to some extent linked with the stage of genetic evolution. However, the associations varied with age, defining two extreme groups. The younger patients (less than 40 years) presented a more complete acquisition of the aggressive phenotype and near-triploid tumors from this group were very frequently steroid hormone receptor-negative, high proliferation, and grade III. By contrast, near-triploid tumors in patients above 65 presented relatively frequently as receptor-positive, low proliferative activity, and even grade I. The correlation of the proliferative status with steroid hormone receptor content led to similar conclusions, high proliferation being more strongly correlated with the absence of estrogen and progesterone receptors in younger patients. Interestingly, the association between high proliferation and negative progesterone receptors was much weaker in patients above 55. Our results suggest that the currently established biological prognostic factors, including DNA profile, steroid hormone receptors, and histopathological grade, show patterns of association which vary with age. Of these, only progesterone receptor could be influenced by menopausal status. These findings have to be taken into consideration for future prognostic factor-related treatment decisions, but also for future methodological improvements of multivariate survival analyses.