Combination Endocrine Therapy in the Management of Breast Cancer

Abstract

Combination endocrine therapy has long been sought after as a means to better treat breast cancer. Agents that suppress estrogen production are given with agents that suppress estrogenic activity at the cellular level. Historically, these combinations have resulted in initial improvements in response rates, but relapse-free and overall survival were not significantly improved. Also, the increased toxicity seen with these regimens was limiting. New endocrine therapies with more potent activity and less toxicity have led to a resurgence of this idea in the management of breast cancer. Complete estrogen blockade has been compared with single-agent treatments in many different settings. The endocrine effects of this type of therapy are intriguing, but apparently do not readily predict a clinical advantage. The combination of an aromatase inhibitor and an antiestrogen, despite pharmacokinetic interactions, may prove to be beneficial. Results from ongoing trials are eagerly awaited to further address this question in postmenopausal breast cancer patients. For premenopausal breast cancer patients the options are more complex. Clinical outcomes with leutinizing hormone releasing hormone (LHRH) agonists plus aromatase inhibitors are limited to very small phase II studies and are not clearly superior to single-agent therapy. Clinical data in the metastatic setting with premenopausal patients favor the use of an LHRH agonist with tamoxifen over the use of an LHRH agonist alone. However, a similar comparison with tamoxifen alone is lacking with only one trial including this as a treatment arm. Adjuvant therapy with this combined endocrine approach (LHRH agonist plus antiestrogen) has been more extensively studied, but lacks crucial comparisons necessary for making complex treatment decisions. Hopefully, through investigative diligence and ingenuity this issue can be adequately understood. However, many exciting new agents are on the horizon that offer hope to further advance the progress made to date although further confounding the questions already answered.

What Is Known about Breast Cancer in Young Women?

“…First-line endocrine therapy for premenopausal MBC is tamoxifen alone or an LHRH agonist alone; although, combination therapy may provide clinical benefit. In a meta-analysis of four studies comparing LHRH agonist with or without tamoxifen in premenopausal women with metastatic breast cancer, there was a statistically significant improved median survival (2.9 years with combination vs. 2.5 years with LHRH agonist alone; p = 0.02) and median PFS with combined therapy versus monotherapy (8.7 vs. 5.4 months, p = 0.0003) [ 285 ]. Similar comparisons of tamoxifen alone versus combination with LHRH agonist have not reported the same findings; however, adding tamoxifen should be considered in patients receiving LHRH agonist given these results.…”

Current State of Breast Cancer Diagnosis, Treatment, and Theranostics

“…Nevertheless, there are conflicting results reported. It is generally believed that patients with endocrine-therapy-naïve advanced breast cancer and those with highly endocrine-sensitive tumors may benefit the most from combination endocrine therapy [ 152 , 153 , 154 , 155 ]. Several other biomarkers have emerged as potential targets for breast cancer therapy as described below.…”

Recent Advances in the Treatment of Breast Cancer

“…Since endocrine drugs work by different mechanisms, they are generally used in combination for better anticancer efficacy. However, conflicting results have been reported ( 10 – 12 ). It is generally believed that patients with endocrine therapy-naïve advanced BC and those with highly endocrine-sensitive tumors may benefit the most from combination endocrine therapy ( 13 ).…”