Several clinical trials have shown that prolonged adjuvant endocrine therapy will benefit some breast cancer patients. Of course, the potential benefit of extended adjuvant endocrine therapy should be weighed against the possible adverse effects for each breast cancer patient. The availability of prognostic molecular tests allows us to distinguish between subgroups of patients who do not require extended endocrine therapy and those who are at low risk of recurrence, and helps us to select the subgroup of patients who are most likely to benefit from extended adjuvant endocrine therapy. This not only prevents patients from receiving unnecessary treatment, but also minimizes the adverse effects of treatment. Preclinical studies have shown clear efficacy of endocrine therapy in the brain, yet the results of related studies are inconsistent. Even more significant differences are reflected in the treatment response to clinical hormonal interventions. Neuropsychological studies suggest that there are cognitive adverse effects of endocrine therapy that originate from specific treatment modalities and are subject to further study. As mentioned above, we need to consider a combination of key mediators and modulators and physical and psychological symptoms (both pre-existing and present during treatment) in order to be able to accurately characterize the cognitive changes that occur in patients and to explore whether there are specific subgroups of patients at high risk. In addition, we should focus on whether the cognitive changes associated with cancer treatment are affecting patients’ daily life. Although the results of neuropsychological tests showed that several aspects of patients’ daily life were affected, such as occupation, treatment compliance and financial status, there are no studies assessing the impact of endocrine therapy on these aspects. Therefore, in addition to statistical significance, a standardized and clear definition of clinical significance should be provided. This will help us to choose the best and safest treatment option for patients to reduce the total physical and psychological burden. The purpose of many clinical trials is to evaluate the efficacy of drugs, and the assessment of drug toxicity in phase I clinical trials is usually limited to directly observed adverse effects. Although trial designs for adjuvant breast cancer treatment could theoretically assess adverse effects of long-term drug use, the results of the studies often cannot be combined. Notably, cognitive effects may occur later in the course of treatment, and these are often rarely documented. Therefore, a comprehensive assessment of these short- and long-term effects, as well as the persistence and reversibility of effects after discontinuation of treatment, is necessary. It would be beneficial to add assessment of cognitive function before, during and after the intervention in large clinical trials, only then can we assess the baseline level of cognition and the (long-term medication) impact on cognition. Unfortunately, few trials now include cognitive assessment in their clinical evaluation. The addition of several evaluation metrics, including patient-based efficacy and direct comparisons of quality of life between treatment groups, in several studies of endocrine therapy for breast cancer provides fertile ground for future trial design improvements. Opportunities and challenges exist for incorporating cognitive assessment into clinical trial design, as shown in the table below. The Response Assessment in Neuro-Oncology Task Force (RANO) and the International Cognition and Cancer Task Force (ICCTF) have proposed a core set of cognitive tests to examine patients’ memory, executive function, and processing speed. These tests have been widely adopted by EORTC, RTOG and other organizations. The inclusion of these tests in future studies will hopefully shed light on the potential adverse effects of endocrine therapy on cognition and help identify specific cognitive characteristics that can be used for testing in the management of breast cancer. In a time when improving clinical prognosis and prolonged patient survival have led to not only the existence but a progressive increase in overtreatment of specific subgroups of patients with breast cancer, it is necessary to focus on the impact of treatment on cognitive function. There is growing evidence of potential adverse cognitive effects of tamoxifen, however, there is uncertainty regarding the adverse cognitive effects of aromatase inhibitors (AI). Little is known about the lack of research in this area, however. The value of adjuvant endocrine therapy in breast cancer treatment goes beyond the discussion itself, as it does improve the prognosis of breast cancer patients and there is no strong evidence to support an adverse cognitive response that would require discontinuation of therapy. We continue to look for prognostic biomarkers to determine whether patients will benefit sufficiently from adjuvant endocrine therapy to make the recommendations more scientifically sound. For patients who are not expected to benefit from adjuvant endocrine therapy, it may be more beneficial for patients not to have such therapy. For patients who can benefit from adjuvant endocrine therapy, it is necessary to systematically observe the occurrence, severity, and cause of each adverse effect (including perceived adverse effects) and to explore ways to potentially reduce these adverse effects and maximize the quality of life for these patients.