Anastrozole and letrozole are both aromatase inhibitors, anti-cancer medications used for treating postmenopausal women with breast cancer. The ATAC (Anastrozole or Tamoxifen Alone or in Combination) trial randomized 9366 postmenopausal women with invasive breast cancer to 5 years of adjuvant anastrozole, tamoxifen, or a combination of the two Baseline characteristics were well balanced across the three groups. Aromatase inhibitors are widely used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. Recent studies have indicated that letrozole and anastrozole appear to be at least as effective as tamoxifen in first-line therapy and may prove to be superior in term of response rates and time-to-disease progression. The average age was 64, one-third of the patients had positive lymph nodes, and 64% had tumors less than 2 cm in size. Toxicity in the combination arm was similar to that seen in the tamoxifen arm After the release of these data, ASCO (American Society of Clinical Oncologists) convened a multidisciplinary panel of experts to conduct a technology assessment on the role of aromatase inhibitors in the adjuvant setting One other study that looked at the use of an aromatase inhibitor in early-stage breast cancer has been reported. These drugs can also cause muscle and joint pain. The study also looked at the incidence of adverse events. Rose Several additional trials are under way comparing aromatase inhibitors in a variety of clinical settings. They originally gained FDA approval on the basis of their efficacy as second-line therapy and their favorable side effect profiles. What are the risks and side effects of aromatase inhibitors? The steroidal inhibitor binds irreversibly to the aromatase enzyme, whereas the nonsteroidal inhibitors form covalent, reversible bonds. The ongoing adjuvant trials have several basic designs: some compare 5 years of adjuvant tamoxifen with an aromatase inhibitor; others look at the use of sequential therapy with tamoxifen and an aromatase inhibitor; and the last group studies tamoxifen followed by an aromatase inhibitor The aromatase inhibitors have proven to be very active drugs in the treatment of hormone receptor-positive breast cancer. Given their efficacy and lack of significant side effects, the aromatase inhibitors have largely replaced megestrol as second-line hormonal therapy for metastatic breast cancer. There were significantly more patients with ER/PR unknown tumors in the TARGET trial. The most common side effects of AIs are symptoms of menopause, such as hot flashes, night sweats, and vaginal dryness. These trials aim to demonstrate which hormonal therapy leads to the lowest rates of breast cancer recurrence and produces the most favorable side effect profile. If you find that the side effects are keeping you from taking the hormone therapy that you were … Studies have shown no impact on cortisol or aldosterone levels in patients being treated with 3–10 mg/day anastrozole for up to 3 months Only one study has compared the clinical efficacy of third-generation aromatase inhibitors. A meta-analysis pooled data from three of these large randomized trials comparing aromatase inhibitors to megestrol Several large randomized trials have compared the third-generation aromatase inhibitors to tamoxifen for first-line treatment of metastatic breast cancer Anastrozole has been compared with tamoxifen as first-line treatment for metastatic breast cancer in two large randomized trials and one smaller trial. This side effect can be serious enough to cause some women to stop taking the drugs. Results from this trial are not yet available. There was a statistically significant improvement in DFS in the patients treated with anastrozole as compared with tamoxifen, with a hazard ratio of 0.83 (95% CI, 0.71–0.96). Almost all the women reported experiencing at least one of the 38 side effects listed in the survey. Patients whose tumors overexpressed HER2/neu (14% of tumors) were significantly less likely to respond to tamoxifen as compared with patients whose tumors did not overexpress HER2/neu (17 These studies suggest that the aromatase inhibitors may be useful in the treatment of early-stage breast cancer. ; Side effects of anastrozole and letrozole that are similar include nausea, vomiting, and headache. In the United States, three third-generation aromatase inhibitors are available commercially: anastrozole, letrozole, and exemestane. There was no difference in DFS between the combination arm and the tamoxifen arm. Milla-Santos As a result of these trials, anastrozole gained an FDA indication for first-line treatment of metastatic breast cancer.Letrozole has been demonstrated to have superior efficacy to tamoxifen as first-line treatment for metastatic breast cancer.