Increasing protection after tamoxifen: insights from the extended adjuvant aromatase inhibitor trials

Abstract

For disease-free postmenopausal women with hormone-responsive breast cancer, a risk for relapse remains following 5 years of adjuvant therapy with tamoxifen. Additional therapy with tamoxifen beyond 5 years is not indicated due to a demonstrated lack of efficacy beyond this time frame. Thus, there is a need for other endocrine therapy options in the period beyond 5 years. The third-generation aromatase inhibitors (anastrozole, letrozole, and exemestane) have emerged as at least as effective and somewhat better tolerated alternatives to tamoxifen. Three trials were initiated to evaluate the efficacy and tolerability of aromatase inhibitors in the extended adjuvant setting. Among these, the large, double-blind, randomized, placebo-controlled MA.17 trial has already demonstrated a significant benefit of letrozole when compared with placebo on disease-free survival in postmenopausal women previously treated for 4.5-6 years with tamoxifen. A smaller open-label trial, the Austrian Breast and Colorectal Cancer Study Group 6a has reported a significant benefit for anastrozole on recurrence when used as extended adjuvant therapy when compared with no treatment, and similar results have been seen with extended adjuvant exemestane in the National Surgical Adjuvant Breast and Bowel Project B-33 trial. The results of these trials have important clinical implications for the future of extended adjuvant hormonal therapy for breast cancer.

Cysteinyl leukotriene receptor expression pattern affects migration of breast cancer cells and survival of breast cancer patients

“…Nevertheless meta‐analyses or overviews that combine results from several parallel studies demonstrate the favorable effects of tamoxifen as an adjuvant treatment in ER‐positive breast cancer 32. Five years has been determined to be the optimal duration for tamoxifen treatment 33, 34. However, our data suggest that prolonged tamoxifen treatment might also be beneficial.…”

Combined effects of goserelin and tamoxifen on estradiol level, breast density, and endometrial thickness in premenopausal and perimenopausal women with early-stage hormone receptor-positive breast cancer: a randomised controlled clinical trial

“…Thus TAM, the most commonly used hormonal treatment for breast cancer patients, was introduced into clinical practice in the 1970s and has substantially improved survival duration in patients with hormone receptor-positive breast cancers (Jaiyesimi et al , 1995; O'Regan and Jordan, 2002; Breast International Group (BIG) 1-98 Collaborative Group et al , 2005; Clarke, 2008; Rose, 2008; Masuda et al , 2012). However, TAM is also able to produce notable estrogenic effects on the skeletal system, lipid metabolism, and various gynaecological tissues, including mammary gland, vaginal mucosa, and uterus (Arimidex, Tamoxifen, Alone or in Combination Trialists' Group, 2006; Rose, 2008; Melnikow, 2010). Although TAM can improve survival duration in patients with estrogen-sensitive breast cancer, its long-term use inevitably increases the risk of adverse effects, such as endometrial cancer and disorders of lipid metabolism (Gardner et al , 2000; Nystedt et al , 2000; Weitzel et al , 2007).…”