Anastrazole superior to tamoxifen for breast cancer treatment [Classics Series]

Classics Series, Landmark Trials in Medicine

1. Postmenopausal women with advanced breast cancer randomized to anastrazole as first-line therapy experienced an increase in time to progression and a more favorable side effect profile compared to women randomized to tamoxifen treatment.

Original Date of Publication: November 2000

Study Rundown: Postmenopausal breast cancer is classically a hormone-responsive disease whereby the majority of tumors require estrogen stimulation to grow. Tamoxifen is a selective estrogen receptor modulator (SERM) that antagonizes estrogen receptors in the breast and uterus and acts as an agonist, or activator, of estrogen receptors in bone. In the treatment of postmenopausal breast cancer, chemotherapy and endocrine treatment in the form of tamoxifen therapy has been shown to be beneficial. While tamoxifen has been demonstrated to prolong survival and reduce incidence of contralateral breast tumors, its use is also associated with a 2-3 fold increased risk of developing endometrial cancer. Further, while tamoxifen is an estrogen receptor antagonist in the breast, it can also act as a partial agonist such that it may not maximally suppress the effects of estrogen. In the late 1990s, researchers hypothesized that aromatase inhibitors, which inhibit aromatase and thus block the conversion of androgens to estrogens in the peripheral adipose, might allow for more complete estrogen suppression. Anastrazole (also known as arimidex) is an aromatase inhibitor that demonstrated promise in prolonging survival in women with advanced stage breast cancer. In the present work, researchers conducted a large international randomized trial to compare the efficacy and tolerability of anastrazole and tamoxifen among women with advanced postmenopausal breast cancer.

Results of the present work represent the North American arm of the TARGET trial (Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability Study), a large international study comparing the efficacy and tolerability of these 2 drugs as first-line treatment of advanced breast cancer in 668 postmenopausal women. Findings demonstrated that anastrazole was at least as effective as tamoxifen as first-line therapy for postmenopausal breast cancer and was associated with a significantly increased time to progression and greater clinical benefit. Further, fewer incidents of thromboembolic events and postmenopausal vaginal bleeding were observed in women on anastrazole. Investigation of the efficacy and tolerability of anastrazole for premenopausal breast cancer and for primary chemoprophylaxis in women at high risk for breast cancer (e.g. BRCA carriers, women with ductal carcinoma in situ) is merited.

Click to study in the Journal of Clinical Oncology

In-Depth [randomized controlled trial]: A total of 353 postmenopausal women with advanced breast cancer were randomized across 97 study sites in the United States and Canada to daily treatment with anastrazole 1mg (n=171) or tamoxifen 20mg (n=182) as first-line therapy. Primary outcomes included objective response (OR), time to progression (TTP) and tolerability. Time to treatment failure (TTF), response duration and duration of benefit were also assessed.

Women randomized to anastrazole experienced a longer TTP interval compared to women on tamoxifen (11.1 vs. 5.6 months, respectively, p = 0.005), translating to a tamoxifen:anastrazole hazard ratio of 1.44. The proportion of women with demonstrable clinical benefit was higher in the anastrazole compared to tamoxifen group (59 vs. 46%, p < 0.01). Rates of thromboembolic events and vaginal bleeding were higher in women on tamoxifen.

Image: PD

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