Breast cancer endocrine responsiveness

Adjuvant chemotherapy with cyclophosphamide, methotrexate, and fiuoro-uracil (CMF) in early breast cancer prolongs relapse-free survival and overall survival in premenopausal patients, but has only a slight effect in postmenopausal patients (B9). Because chemotherapy causes ovarian suppression (D2) and breast cancer is responsive to endocrine therapy, it is important to know if, and to what extent, the effect of chemotherapy is mediated by ovarian suppression. The efficacy of ERP/PRP assays in predicting the response of breast cancer to chemotherapy has been studied by many investigators in their search for a marker that would prepict the tumor response. 

In addition, it will be our intention to present a deeper insight into the biosynthesis of steroid hormones, which will allow definition of new targets and approaches for the treatment of endocrine-responsive cancer. Enzymes involved in mechanisms of steroid hormone biosynthesis might be novel targets for endocrine therapy. Moreover, further therapeutic indications for modulators of steroid hormone receptors will be discussed. In summary, many promising new opportunities for endocrine therapy of breast and prostate cancer are now arising. 

One of the earliest examples of predicting efficacy has come from studies of breast cancer, where anti-estrogen therapy is clearly effective in patients whose tumors express the estrogen receptor, and ineffective when no such receptors are present. However, even in this well-studied case, current consensus statements recognize an intermediate endocrine response uncertain state, where the exact boundary between endocrine responsive and endocrine response uncertain is undecided, and may well be different in different clinical settings (19). 

Bieche, I., Parfait, B., Doussal, V. L., Olivi, M., Rio, M.-C., Lidereau, R., and Viduad, M. 2001. Identification of CGA as a novel estrogen receptor-responsive gene in breast cancer An outstanding candidate marker to predict the response to endocrine therapy. Cancer Res. 61 1652-1658. 

Harvey, J. M., Cark, G. M., Osborne, C. K., and Allred, D. C. 1991. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J. Clin. Oncol. 27 1474-1481. 

Zoledronic acid has also been investigated in the prevention of cancer treatment-induced bone loss in 401 premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer in a randomised, open-label. Phase 111 clinical trial [76]. In this study, patients received tamoxifen and goserelin with or without zoledronic acid (4 mg i.v. every 6 months) versus anastrozole and goserelin with or without zoledronic acid (4 mg i.v. every 6 months) for 3 years. The combination of zoledronic acid with endocrine therapy was well tolerated and was not associated with changes in renal function in this patient population. Over 3 years, 2, 904 serum creatinine measurements were taken, the mean serum creatinine level was 0.78 + 0.17 mg/ dl, and no patient had serum creahnine levels that exceeded 1.5 times the upper limit of normal [76]. 

Dehdashti F, et al. PET-based estradiol challenge as a predictive biomarker of response to endocrine therapy in women with estrogen-receptor-positive breast cancer. Breast Cancer Res Treat. 2009 113 509-517. 

Jakesz R, Hausmaninger H, Kubista E, et al. Randomized adjuvant trial of tamoxifen and gosereUn versus cyclophosphamide, mefiiotrexate, and fluorouracil Evidence for file superiority of treatment wifii endocrine blockade in premenopausal patients with hormone-responsive breast cancer— Austrian Breast and Colorectal Cancer Study Group Trial 5. J ain Oncol 2002 20 4621 627. 

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