ABSTRACT
I. ABSTRACT Neoadjuvant protocols allow identification of predictive markers of response to therapy. Indices measured in tumor biopsies taken before and during treatment may be related to response as determined by sequential clinical measurements of tumor size. Studies in which patients have been given a variety of endocrine therapies (surgical/medical castration in premenopausal women and tamoxifen or aromatase inhibitors in postmenopausal women) have confirmed that estrogen-receptor (ER) status is the single best predictor of subsequent benefit, as cancers with poor ER levels rarely respond. Other markers such as progesterone receptors (PgRs) increase discrimination in ER-rich cancers, but not absolutely. It can be shown that changes in cell-cycle parameters precede clinical response and are less likely to occur in nonresponsive cancers. Paradoxical phenotypic changes that occur in “responding” cancers may indicate progression to hormone resistance, being associated with the same increased incidence of early recurrence as nonresponding cancers. Micro-and tissue assays are novel technologies that will be increasingly used to produce RNA and protein profiles of tumor biopsies taken before and during therapy, but their potential has yet to be fully exploited.
