Characterization of steroid hormone sensitivity in human breast cancers maintained ex vivo under organotypical culture conditions

Purpose: The methodology we propose combines the immunohistochemical determ ination of the oestrogen and progesterone receptors (ER and PgR) with the c haracterization of the oestradiol- and progesterone-induced influence on ce ll proliferation in breast cancers in order to characterize their steroid h ormone sensitivity at both the "static" and "dynamic" level. Methods: ER an d PgR have been immunohistochemically quantified by means of computer-assis ted microscopy. Cell proliferation has been determined by means of tritiate d thymidine autoradiography in tumour samples maintained in vitro as organo typic cultures. A series of 14 patients was investigated. Results: Of the 1 4 breast cancers under study, one with an unequivocally "very ER-rich"/"ver y PgR-rich" immunohistochemical phenotype totally failed to exhibit any mod ification in its cell proliferation level after both oestradiol and progest erone stimulation. Two cases definitively associated with an "ER-poor"/"PgR -poor" immunohistochemical phenotype nevertheless responded noticeably to t he dynamic stimulation of their cell proliferation by oestradiol and proges terone. While our series of cases covers 14 patients only, it suffices to d emonstrate the limits of ER and PER determination in characterizing steroid hormone sensitivity in breast cancer. Discussion: The present work therefo re presents an in vitro approach to test growth regulation of human breast cancer by steroid hormones. The clinical value of the present approach shou ld be further determined by showing that steroid hormone-induced modificati ons in cell proliferation level are actually associated with clinical respo nse.