Cognitive changes associated with endocrine therapy for breast cancer

Abstract

Endocrine therapy in the setting of breast cancer has undoubtedly advanced clinical outcomes in this disease, but treatment with endocrine therapy is accompanied by a wide spectrum of side effects. It is of prime importance to understand and characterize these toxicities to facilitate clinical decision-making. Somewhat surprisingly, there is a relative paucity of data pertaining to cognitive changes associated with endocrine therapy. In this article we review cognitive associated with two classes of endocrine therapy: (1) selective estrogen receptor modulators (SERMs; tamoxifen and raloxifene) and (2) aromatase inhibitors (AIs; anastrozole, letrozole, and exemestane). Companion studies to the Multiple Outcome of Raloxifene Evaluation (MORE), the Study of Tamoxifen and Raloxifene (STAR) and National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trials provide relevant data to understand the effect of SERMs on cognition. In contrast, substudies of the Arimidex, Taxmoxifen Alone or in Combination (ATAC), Tamoxifen and Exemestane Adjuvant Multinational (TEAM) and Breast International Group (BIG) 1–98 trials juxtapose cognitive effects of AIs against those of tamoxifen. These and other studies are examined herein to provide a comprehensive overview of the effect of endocrine therapy on cognition.

Alterations in Brain Activation During Working Memory Processing Associated With Breast Cancer and Treatment: A Prospective Functional Magnetic Resonance Imaging Study

“…A growing body of evidence demonstrates that a subgroup of patients with BC have pretreatment cognitive deficits, [1][2][3][4][5] suggesting that aspects of cancer pathogenesis or host factors (potentially including variables related to BC surgery) cause cognitive changes or that there are common risk factors for the development of cancer and cognitive changes. 6 Prospective studies have shown cognitive changes differentially attributable to chemotherapy, radiation, and antiestrogen treatment, [7][8][9][10][11] highlighting the need for better understanding of potentially additive and dissociable effects of cancer treatments and the disease process on cognition in vulnerable individuals. 12 Structural and functional neuroimaging allow examination of the neural substrates of cancer-and treatment-related cognitive changes, which currently are poorly understood.…”

Brain health and cognitive and mood disorders in ageing women

“…Ostensibly, the brain uses the available androgen for local synthesis of oestrogen; however, the amounts and effects of post-menopausal brain aromatisation are not known. As the treatment of ageing women with aromatase blockers during anti-breast cancer treatment has been shown not to affect cognition [72], it seems that oestrogen is not the major influence on cognition that it was once considered to be. This is consistent with the findings of many on the effects of oestrogen treatment after the lack of oestrogen is established.…”

The Confounding Factor of Apolipoprotein E on Response to Chemotherapy and Hormone Regulation Altering Long-Term Cognition Outcomes

“…A subset of the National Surgical Adjuvant Breast and Bowel Project (NSABP) Study of Tamoxifen and Raloxifene (STAR), the CoSTAR study for women at high risk for breast cancer did not find any cognitive effects of either drug (Table 1) [45]. Together the evidence supports that raloxifene treatment does not impair cognitive function the way that tamoxifen treatment and in fact may even lower the risk of cognitive decline [34].…”

“…There data suggests that arimidex was the preferred initial treatment by women treated for breast cancer [32]. However, other studies indicate that women on arimidex treatment had greater cognitive decline than tamoxifen treatment in verbal and visual memory (Table 1) [33,34]. At this point no effects have been seen on cholesterol, lipoproteins or apolipoprotein levels in both animal models and clinical studies (Table 1) [35,36].…”