Aromatase inhibitors (AIs) are recommended for the treatment of estrogen-sensitive breast cancer in postmenopausal women and provide a superior risk reduction compared to five years of tamoxifen alone. Arthralgias, a common side effect of AIs, may adversely affect quality of life, treatment adherence, and persistence. Early discontinuation of AIs may result in an inadequate clinical response. O...

Recent advances have been made in the hormonal treatment of breast cancer with the advent of third-generation aromatase inhibitors (anastrozole, letrozole, and exemestane). These newer agents have substantial antitumor activity and appear to be as effective as tamoxifen, with fewer adverse effects. Recent reports indicate that anastrozole is more effective than tamoxifen as adjuvant endocrine t...

Aromatase inhibitors are the most important targets in treatment of estrogen-dependent cancers. In order to search for potent steroidal aromatase inhibitors (SAIs) with lower side effects and overcome cellular resistance, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of SAIs to build 3D QSAR models. The rel...

The treatment of postmenopausal women with breast cancer presents a number of challenges. Tamoxifen has had a substantial impact on mortality in women with early-stage, estrogen-receptor-positive tumors. Despite the improvement in the treatment of breast cancer, many patients will ultimately experience a recurrence. Present treatment approaches can provide effective palliation in the advanced d...

We examined published reports on the use of aromatase inhibitors in postmenopausal patients with hormone receptor-positive breast cancer. Our data were obtained through a MEDLINE search of literature published in English. Current data indicate that aromatase inhibitors are equivalent or superior to tamoxifen as first-line therapy for metastatic breast cancer and as neoadjuvant treatment for pri...

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...

To the Editor: We have read with great interest the recently published article by Gerber et al. (1) on the potential endometrial benefit of anastrozole given to postmenopausal breast cancer patients with tamoxifen-induced endometrial pathology. Their study showed that the switch to anastrozole significantly reduced the need for a second invasive gynecologic procedure for recurrent vaginal bleed...

Concurrent inhibition of aromatase and steroid sulfatase (STS) may provide a more effective treatment for hormone-dependent breast cancer than monotherapy against individual enzymes, and several dual aromatase-sulfatase inhibitors (DASIs) have been reported. Three aromatase inhibitors with sub-nanomolar potency, better than the benchmark agent letrozole, were designed. To further explore the DA...

Endometriosis is a common, chronic and estrogen-dependent gynaecological disorder associated with pelvic pain and infertility. In addition to, or perhaps as a consequence of, immune, environmental and genetic factors, endometriotic lesions show high estradiol (E(2)) biosynthesis and low E(2) inactivation compared with normal endometrium. Current medical therapies of pain, which aim to lower cir...

Recently, it was discovered that 4-hydroxy-4-androstene-3,17-dione, 4-androstene-3,6,17-trione, and 1,4,6-androstatriene-3,17-dione, compounds previously reported to be competitive inhibitors of aromatase, cause a time-dependent loss of aromatase activity in human placental microsomes. We report here that 1,4-androstadiene 3,17-dione (Ki 0.32 microM; kinact 0.91 X 10(-3)/sec) and testolactone (...