We describe the case of a 56-year old woman with no prior psychiatric history who was diagnosed with hormone receptor positive early-stage breast cancer and who developed severe mood changes after administration of anastrozole, which resolved after discontinuation of treatment. Aromatase inhibitors (AIs) are the preferred hormonal approach for postmenopausal women with estrogen hormone sensitive breast cancer. The third-generation agents (anastrozole, letrozole, and exemestane) have been shown to be more effective and safer than the selective estrogen receptor modulators tamoxifen and raloxifen. Treatment strategies with these agents include the use of an AI as an upfront strategy for 5 years, as a sequential approach after 2–3 years of tamoxifen, or as extended use after the classical 5 years of tamoxifen. The side effects of AIs, as compared with selective estrogen receptor modulators, are different, reflecting the specific mechanism of action of these drugs. AIs are well tolerated and cause a lower incidence of gynecological symptoms (vaginal bleeding, discharge, and endometrial neoplasia), venous thromboembolic events, and hot flashes compared with tamoxifen. However, the use of AIs have been associated with loss of bone density, arthralgia, myalgia, a negative effect on lipid metabolism, and cardiovascular risk (Tomao et al., 2011). Mood disturbances, somnolence, anxiety, fatigue, hot flashes, and memory impairment have been reported among patients receiving anastrozole as adjuvant therapy.

Tamoxifen can be considered a classic ‘pro-drug’, requiring metabolic activation to elicit pharmacological activity. Our findings suggest that both genetic and drug-induced factors that alter CYP2D6 enzyme activity influence the clinical response to tamoxifen. Given the small differences in disease-free survival comparing tamoxifen to third-generation aromatase inhibitors, knowledge of the genetic and environmental factors that influence CYP2D6 enzyme activity may provide a robust tool to individualize the hormonal therapy to breast cancer.

Endocrine therapy is now established as the treatment option of choice for postmenopausal women with hormone receptor-positive advanced breast cancer. The benefit of the third-generation aromatase inhibitors (AIs) in this setting has prompted their evaluation in the treatment of early breast cancer. This article reviews the current clinical status of AIs as adjuvant therapy for early-stage breast cancer in postmenopausal women, focusing on the largest adjuvant breast cancer study till date to provide data, the ‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial.