GENETIC EVOLUTION OF BREAST CANCERS .3. AGE-DEPENDENT VARIATIONS IN THE CORRELATIONS BETWEEN BIOLOGICAL INDICATORS OF PROGNOSIS

The influence of age on the occurrence of phenotypic features of progn ostic significance was studied in relation to the DNA index values, me asured 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 estro gen receptor-negative and high proliferative activity cases with incre asing age. When analyzed according to the DNA index classes, all param eters were found to some extent linked with the stage of genetic evolu tion. However, the associations varied with age, defining two extreme groups. The younger patients (less than 40 pears) presented a more com plete acquisition of the 'aggressive' phenotype and near-triploid tumo rs from this group were very frequently steroid hormone receptor-negat ive, high proliferation, and grade III. By contrast, near-triploid tum ors in patients above 65 presented relatively frequently as receptor-p ositive, 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 correl ated with the absence of estrogen and progesterone receptors in younge r 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 prog nostic 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 menop ausal status. These findings have to be taken into consideration for f uture prognostic factor-related treatment decisions, but also for futu re methodological improvements of multivariate survival analyses.