The prediction of hormone-dependence in mammary cancer
A review has been made of the literature concerning clinical response rates to endocrine therapies for advanced mammary cancer and the need for a predictor of response has been identified. Various postulated predictors of response have been critically reviewed and Oestrogen Receptor (E/R) status has been identified as the best, currently available, approach. The main limitations of E/R status are, firstly, the poor predictive value of a positive result and, secondly, the complex nature of current techniques for its determination. Two approaches to the prediction of hormone-dependence, aimed at overcoming these limitations of E/R status, have been invest¬ igated. Biochemical and histochemical systems for the identif¬ ication of tissue peroxidase, a postulated, alternative marker for oestrogen-dependence, have been established. Peroxidase levels have been measured in a range of normal rat tissues, in rat mammary tumour models of hormone-dependent and -independent growth and in human mammary tumours and have been compared with levels of E/R and also of Progestogen Receptor (Pg/R). A relationship between peroxidase activity and hormone-dependence has been confirmed but the predictive value of peroxidase determination appears to be inferior to that of E/R assay. The feasibility of a histochemical approach to the identification of E/R has been investigated. The effects of histochemical processing, including methods of tissue fixation, on E/R activity have been studied using tritiated oestradiol as tracer. Conjugates of oestradiol with tracers which can be visualised under the light,or fluorescence, microscope have been synthesised and evaluated. It has been demonstrated that histochemical processing results in considerable losses of detectable E/R activity and £hat oestradiol labelled with histochemical tracers has a very small ability to bind to E/R. Nevertheless, uptake of labelled oestradiol by oestrogen-target tissues, including some human mammary cancers, has been demonstrated and such uptake may be related to bona fide E/R activity.