PURPOSE Treatment-emergent symptoms with adjuvant tamoxifen and aromatase inhibitors (AIs) have been associated with superior recurrence-free survival (RFS). We hypothesized that MA.27 anastrozole- or exemestane-treated patients with new or worsening vasomotor and/or joint symptoms would have improved RFS. PATIENTS AND METHODS MA.27 randomly assigned 7,576 postmenopausal women with breast can...

The traditional hormonal cascade of the 1970s and 1980s used tamoxifen followed by megestrol acetate and subsequently by aminoglutethimide. In the 1990s, however, three trials of third-generation aromatase inhibitors (AIs) compared with megestrol acetate and two trials of third-generation AIs compared with aminoglutethimide showed improved efficacy and decreased toxicity for the newer AIs. Thus...

Human aromatase (CYP19A1) is a steroidogenic cytochrome P450 converting androgens into estrogens. No ligand-free crystal structure of the enzyme is available to date. The crystal structure in complex with the substrate androstenedione and the steroidal inhibitor exemestane shows a very compact conformation of the enzyme, leaving unanswered questions on the conformational changes that must occur...

BACKGROUND Endocrine therapy was recommended as the preferred first-line treatment for hormone receptor-positive (HR+, i.e., ER+ and/or PgR+), human epidermal growth factor receptor-2-negative (HER2-) postmenopausal advanced breast cancer (ABC), but which endocrine monotherapy is optimal lacks consensus. We aimed to identify the optimal endocrine monotherapy with a network meta-analysis. METH...

With recent results showing letrozole and anastrozole to be superior to tamoxifen as initial therapy for advanced disease, the aromatase inhibitors are poised to establish their place in the adjuvant therapy of postmenopausal receptor-positive breast cancer. A review of the rationale, design, and preliminary results of the ongoing adjuvant trials that include aromatase inhibitors will be presen...

BACKGROUND Current approaches to diagnosing testosterone deficiency do not consider the physiological consequences of various testosterone levels or whether deficiencies of testosterone, estradiol, or both account for clinical manifestations. METHODS We provided 198 healthy men 20 to 50 years of age with goserelin acetate (to suppress endogenous testosterone and estradiol) and randomly assign...

BACKGROUND Since PI3K/AKT/mTOR pathway activation diminishes the effects of hormone therapy, combining aromatase inhibitors (anatrozole) with mTOR inhibitors (everolimus) was investigated. PATIENTS AND METHODS We evaluated anastrozole and everolimus in 55 patients with metastatic estrogen (ER) and/or progesterone receptor (PR)-positive breast and gynecologic tumors. Endpoints were safety, ant...

For the first time in 20 years, another class of drugs—aromatase inhibitors— is challenging tamoxifen as the treatment of choice for postmenopausal women with early breast cancer. However, the higher cost of at least one of the aromatase inhibitors and the lack of a statistically significant advantage in breast cancer survival give some researchers pause in wholeheartedly endorsing the drugs. F...

Antiestrogens and aromatase inhibitors are important drugs in the treatment of estrogen-dependent breast cancer. To investigate the effects of these drugs on gene expression in breast cancer cells, we treated estrogen receptor-positive MCF-7 cells stably transfected with the aromatase gene (known as MCF-7aro cells) with testosterone, 17 beta-estradiol, two aromatase inhibitors (letrozole and an...