Aromatase inhibitors (AIs), which block the conversion of androgens to estrogens, are used for hormone-dependent breast cancer treatment. Exemestane, a steroidal that belongs to the third-generation of AIs, is a mechanism-based inhibitor that binds covalently and irreversibly, inactivating and destabilizing aromatase. Since the biological effects of exemestane in breast cancer cells are not tot...

PURPOSE We conducted a pilot study assessing the effects of the selective estrogen receptor modulator, tamoxifen, on the pharmacokinetics, pharmacodynamics, and safety of the steroidal, irreversible aromatase inhibitor (AI), exemestane, when the two were coadministered in postmenopausal women with metastatic breast cancer. EXPERIMENTAL DESIGN Patients with documented or unknown hormone recept...

Patients' preferences increasingly play roles in cancer treatments. The objective of this study is to examine breast cancer patients' preferences and willingness-to-pay (WTP) for postmenopausal hormone receptor-positive, HER2-negative advanced breast cancer treatments after failure of standard treatments. Four attributes, i.e. progression free survival (PFS), anemia, pneumonitis, and cost, and ...

BACKGROUND Adjuvant treatment of hormone receptor-positive breast cancer in postmenopausal women with aromatase inhibitors may be associated with increased bone loss. PATIENTS AND METHODS Two hundred patients were randomised to receive exemestane or tamoxifen as adjuvant treatment of hormone receptor-positive breast cancer. Bone mineral density (BMD) was assessed by dual-energy X-ray absorpti...

PURPOSE Tremelimumab is a fully human monoclonal antibody specific for CTL-associated antigen 4 (CTLA4) with single-agent activity in certain tumors but has not been evaluated in patients with breast cancer. EXPERIMENTAL DESIGN In a phase 1 study, 26 patients with advanced, hormone-responsive breast cancer received tremelimumab (3-10 mg/kg) every 28 days or every 90 days plus exemestane 25 mg...

The third-generation aromatase inhibitors (AIs: anastrozole, letrozole, and exemestane) have now become standard adjuvant endocrine treatment for postmenopausal estrogen receptor-positive breast cancer complementing chemotherapy and surgery. Because of the absence of direct head-to-head comparisons of these AIs, an indirect comparison is needed for individual treatment choice. In this network s...

BACKGROUND The antiestrogen tamoxifen may have partial estrogen-like effects on the postmenopausal uterus. Aromatase inhibitors (AIs) are increasingly used after initial tamoxifen in the adjuvant treatment of postmenopausal early breast cancer due to their mechanism of action: a potential benefit being a reduction of uterine abnormalities caused by tamoxifen. PATIENTS AND METHODS Sonographic ...

Breast cancer is the most prevalent cancer in women, causing a significant mortality worldwide. Different endocrine strategies are available for the treatment of hormone-sensitive breast cancer, including antiestrogen tamoxifen and fulvestrant, as well as third-generation aromatase inhibitors (AIs), such as letrozole, anastrozole, and exemestane. In this review, we will focus on exemestane, its...

Exemestane is an aromatase inhibitor widely used for the treatment of postmenopausal breast cancer patients. Several precursors are used for its synthesis; however the final step is C-1(2) dehydrogenation of the resultant steroid to yield exemestane. A sequence of hazardous chemical reactions is required for the final step of dehydrogenation. The present work was carried out to replace the chem...

Exemestane is a potent and irreversible steroidal aromatase inhibitor drug used for the treatment of estrogen receptor-positive breast cancer. Our aim was to identify and assess the contribution of the specific P450s responsible for exemestane primary in vitro metabolism. Using HPLC and LC-MS/MS analytical techniques, 17-hydroexemestane (MI) and 6-hydroxymethylexemestane (MII) formation were fo...