ŒSTROGEN FRACTIONS DURING EARLY REPRODUCTIVE LIFE IN THE ÆTIOLOGY OF BREAST CANCER

Abstract

Experimental studies have shown that, when combinations of the oestrogen fractions are administered, the net effect is influenced by the relative amounts of the several fractions as well as by the total dose. Specifically, it appears that the non-carcinogenic, impeded fraction (œstriol) partly inhibits the action of the carcinogenic, unimpeded fractions (oestrone, œstradiol). However, attempts to demonstrate differences in the ratio of impeded to unimpeded oestrogens between breast cancer cases and controls have been inconclusive. Epidemiological evidence suggests that early reproductive life is a time when events of significance to future breast-cancer risk occur. In particular, pregnancy at a young age is associated with both favourable oestrogen fraction ratios and decreased breast-cancer risk. We therefore suggest that the relative levels of the individual oestrogen fractions produced in the first decade or so after puberty are important determinants of a woman's life-time breast-cancer risk. This hypothesis allows reconciliation of several sets of observations which have previously seemed inconsistent, including the varied results of case-control studies. While a direct test of this hypothesis is not likely to be forthcoming in the next decade, several investigations could be undertaken immediately to provide persuasive evidence for or against it.