May Endocrine Therapy be Associated with Cognitive Impairment in Breast Cancer Patients?

Background: Endocrine Therapy (ET) is a mainstay in Hormone Receptor-positive Breast Cancer treatment. The ability to counter estrogenic signaling in mammary tissue has made Selective Estrogen Receptor Modulators, Aromatase Inhibitors and the Selective Estrogen Receptor Degrader fulvestrant essential therapies in both early and late stage settings, with good safety profiles and benefit/ risk ratios. Nonetheless, numerous tissues are affected by estrogen stimulation, and diverse adverse drug events have emerged. The Central Nervous System appears to be affected as well and claims of cognitive impairment following endocrine therapy have arisen. Objective: The study aimed to discuss the available evidences on the possible association of ET to cognitive impairment in breast cancer patients, gathering up-to-date information from clinical trials, meta-analysis, as well as expert opinions. Method: Appropriate and pertinent articles were retrieved through PubMed search. Results: Controversial data emerged from clinical trials as well as observational studies and metaanalysis. Many authors have shown that verbal memory is negatively affected by exposure to tamoxifen. Moreover, significant lower memory test scores in the aromatase inhibitor-treated patients have been reported. On the other hand, there are clinical and preclinical evidence suggesting that tamoxifen may have a protective role in the Central Nervous System. Conclusion: To date, the association between ET and cognitive impairment has not yet been proven. Future studies on available and upcoming drugs will need to include proper cognitive evaluation scales and an adequate number of participants in order to better define the role of ET in the possible development of cognitive impairment in breast cancer patients.