Adjuvant Hormonal Therapy: Current Standard and Practical Issues

Abstract

Adjuvant hormonal therapy is used as the first target-specific approach in curing breast cancers due to its high efficacy and mild side effects. Five years of tamoxifen therapy has been the gold standard for women with estrogen receptor-positive breast cancer irrespective of age or menopausal and nodal status. After the emergence of 3rd generation aromatase inhibitors (AI), the use of either tamoxifen or tamoxifen plus ovarian function suppression for 5 years has been proposed as an acceptable standard for premenopausal women while AI should form part of standard endocrine therapy for the postmenopausal women as established at the St. Gallen Concensus Conference. The addition of luteinizing-hormone-releasing hormone (LHRH) analogs might be beneficial for the younger patients who remain premenopausal after chemotherapy, however controversies over the addition of LHRH analogs remains. Further, it has been suggested that CYP2D6 polymorphisms and concomitant use of CYP2D6 inhibitors which reduce CYP2D6 activity may influence the clinical outcomes of adjuvant tamoxifen therapy. The androgen receptor has been evaluated as a prognostic or predictive marker for endocrine responsiveness in a few studies; however, there are many issues to be answered and ongoing clinical trials will provide the answers. Until then, it would be important for clinicians to carefully evaluate the risk factors of patients, monitor the compliance of those patients who are under endocrine therapy, and take care in selecting antidepressants when coprescription with tamoxifen is necessary. In the future, tailored therapy will be designed based on the target molecular profiling of the tumors, pharmacogenomics, and improved understanding of receptor signaling biology. More attention should be given to explore molecular markers that could differentiate the subsets for tailoring