Aromatase inhibitors (AIs) are the preferred hormonal therapy for postmenopausal women with estrogen sensitive breast cancer.  While the selective estrogen receptor modulators (SERMs), such as tamoxifen and raloxifene, are used in premenopausal women with estrogen sensitive breast cancer, the aromatase inhibitors (e.g., anastrozole, letrozole, and exemestane) have been shown to be more effective and safer than the SERMs in postmenopausal women.

Because estrogen is known to have a positive effect on mood, it is reasonable to assume that these hormonal therapies that suppress estrogen activity might have the opposite effect.  A recent article reviews the side effects commonly reported in women treated with these hormonal treatments, including hot flashes and mood changes.  This article discusses a case of a 56-year-old woman with no prior psychiatric history who develops severe mood changes after treatment with anastrozole.  The symptoms of depression resolve after discontinuation of treatment.

In summary:

  • Mood disturbances, anxiety, fatigue, hot flashes, and memory impairment have been reported among women receiving AIs and tamoxifen
  • AIs are associated with a lower incidence of gynecological symptoms (e.g., vaginal bleeding, discharge, and endometrial neoplasia), venous thromboembolic events, and hot flashes compared to tamoxifen.
  • AIs have been associated with reductions in bone density, arthralgia, myalgia, negative effects on lipid metabolism, and increased cardiovascular risk.

Exactly how frequently depression occurs in women treated with these hormonal therapies has not been well-studied. Clinically depression is observed in some breast cancer patients receiving hormonal therapies.  Large clinical trials have yielded generally positive results regarding the risk of depression in women treated with tamoxifen.  In the Study of Tamoxifen and Raloxifene (STAR), women at high risk for breast cancer received tamoxifen (n = 973) or raloxifene (n = 1010).  Depressive symptoms initially increased after the start of therapy, followed by a partial return to baseline levels. The change was small (e.g., about 1.5 points in CES-D scores).

Less data is available regarding the use of AIs.  One study of Japanese women treated with anastrozole demonstrated no significant change in depressive symptoms (as measured using the CES-D) at one year after initiation of treatment versus baseline.

The data suggest that mood changes are not commonly associated with hormonal therapies for breast cancer.  This is reassuring; however, we do know that depression is relatively common in women diagnosed with breast cancer.  Whether the depression stems from the effects of hormonal modulation or other factors, for instance, the burden of having a life-threatening illness, we must recognize that this population of women is at high risk for psychological distress and depression and should be routinely assessed.

Ruta Nonacs, MD PhD

Fann JR, et al. Major depression after breast cancer: A review of epidemiology and treatment. Gen Hosp Psychiatry. 2008;30:112–26.

Land SR, et al. Patient-reported symptoms and quality of life during treatment with tamoxifen or raloxifene for breast cancer prevention: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA. 2006;295:2742–2751.

Reich M, et al. Depression, quality of life and breast cancer: A review of the literature. Breast Cancer Res Treat. 2008;110(1):9–17.

Rocha-Cadman X, et al. Aromatase inhibitors and mood disturbances. Palliat Support Care. 2012; 10(3):225-7.

Takei H, et al. Health-related quality of life, psychological distress, and adverse events in postmenopausal women with breast cancer who receive tamoxifen, exemestane, or anastrozole as adjuvant endocrine therapy: National Surgical Adjuvant Study of Breast Cancer 04 (N-SAS BC 04). Breast Cancer Research and Treatment. 2012;133(1):227–236.