Adherence studies have shown that adherence to long-term endocrine therapy is not encouraging. A study of TAM adherence in more than 2300 patients found that adherence was 83% in the first year of use and decreased to 50% in the fourth year. Another study of compliance with aromatase inhibitors in more than 1,200 patients also showed that patient compliance decreased each year. The main reason for non-adherence was due to adverse drug reactions. Selective estrogen receptor modulators and aromatase inhibitors have different mechanisms of action and exhibit different adverse effects. Adverse reactions mainly occur in the bone, joint muscle, gynecological and cardiovascular systems. Bone adverse reactions Because lower estrogen levels are significantly associated with an increased risk of fracture, the risk of natural fracture is twice as high in normal postmenopausal women as in men. There are many risk factors for bone loss in breast cancer patients during treatment, including postmenopausal status, aromatase inhibitor therapy, chemotherapy, oophorectomy or application of drugs to suppress ovarian function artificially induced to postmenopausal status. Breast cancer survivors have a 31% increased risk of fracture compared to women without tumors. TAM has estrogen-like effects and is therefore protective of bone, while third-generation aromatase inhibitors such as anastrozole, letrozole, and exemestane can lead to bone loss, osteoporosis, and an increased incidence of fracture. How to reduce bone loss is an area of research that is currently receiving a lot of attention. To reduce osteoporosis and bone loss, breast cancer patients treated with third-generation chemoenzymes inhibitors should routinely consume calcium and vitamin D, increase physical activity, prevent falls, and reduce tobacco and caffeine intake to prevent or slow down osteoporosis and bone; and they should receive regular bone density testing. For breast cancer patients presenting with severe osteoporosis, the current drug of choice is bisphosphonates, as estrogen is contraindicated. Several randomized, multicenter, large clinical studies, Z-FAST (Zometa Femara Adjuvant Synergy Trial) and the ZO-FAST series, have investigated the effect of concomitant application of the bisphosphonate agent zoledronic acid on bone mineral density in patients on long-term aromatase inhibitors. The results showed that patients in the zoledronic acid group had significantly higher BMD and lower fracture rates than those in the non-zoledronic acid group. In recent years, a new drug denosumab, an inhibitor of receptor activator for nuclear factor-kB ligand (RANKL), has been developed to target new bone metabolic pathways and inhibit osteoclast activity. Denosumab significantly improved bone mineral density in breast cancer patients compared to placebo. The American Society of Clinical Oncology guidelines for the evaluation and treatment of bone health in breast cancer patients state that risk factors for osteoporosis in breast cancer patients include: (1) women >65 years of age; (2) women 60 to 64 years of age with a family history, weight <70 kg, previous history of non-traumatic fracture or other risk factors; (3) postmenopausal women treated with aromatase inhibitors; (4) women treated with treatments such as chemotherapy leading to premature menopause. For high-risk patients, dual-energy x-ray bone densitometry scans of the hip and/or spine are recommended to screen for bone density. 2011 Chinese Anti-Cancer Association guidelines and specifications for breast cancer diagnosis and treatment also recommend patients using aromatase inhibitors to undergo bone density testing every 6 months, and if the T-score is <-2.5, bisphosphonates are recommended; if the T-score is -1.0 to -2.5, bisphosphonates can be considered; if the T-score is -1.0 to -2.5, bisphosphonates can be considered. If the T score is -1.0 to -2.5, bisphosphonates may be considered; if the T score is > -1.0, bisphosphonates are not recommended; vitamin D and calcium are routinely administered for T scores ≤ -1.0. Joint muscle symptoms The incidence of joint, muscle and bone pain gradually increases with age in healthy women, peaking at menopause, suggesting that bone, joint and muscle symptoms are associated with declining estrogen levels. The incidence of joint pain was significantly higher in patients in the aromatase inhibitor treatment group than in the TAM group. The incidence of bone, joint and muscle pain has been reported to reach up to 60% in breast cancer patients treated with aromatase inhibitors, and the rate of drug discontinuation can reach 20%. Some patients have also experienced a reduction in pain symptoms with longer duration of drug use. Therefore, before and during the start of aromatase inhibitor therapy, patients should be evaluated for bone and joint muscle symptoms to exclude pain caused by bone metastases, osteoarthritis and rheumatoid arthritis. For pain caused by aromatase inhibitors, vitamin D and calcium supplements and appropriate physical exercise can be given to mild cases; NSAIDs can be given to those with significant pain. Patients may also be considered for a 3- to 4-week drug holiday (i.e., a period of discontinuation of the drug). In addition, since the 3 commonly used aromatase inhibitors do not have exactly the same mechanism of action, switching to endocrine drugs with other mechanisms of action may also be considered. Gynecological adverse reactions Because TAM has estrogen-like effects, long-term use may lead to adverse reactions such as hot flashes, vaginal bleeding, endometrial thickening, uterine fibroids, and ovarian cysts. A serious adverse effect is the possibility of endometrial cancer, but the incidence is low, about 0.3%. Therefore, patients without menstruation who have been using TAM for a long time should have their endometrial thickness checked by ultrasound regularly and the thickened endometrium should be treated if necessary. Aromatase inhibitors, in contrast to TAM, have a lower incidence of the above gynecological problems, usually accompanied by vaginal dryness and decreased libido. A questionnaire survey of breast cancer patients aged 35 to 65 years who were treated with TAM was conducted to investigate the incidence of these problems. Plant-based medications, such as black asclepias isopropyl alcohol extract, are also available to reduce menopausal symptoms by modulating neurotransmitters. Adverse cardiovascular system reactions The cause of death in breast cancer patients may be cancer recurrence or cardiovascular disease. Elevated cholesterol, triglycerides, LDL and reduced HDL are all risk factors for the development of cardiovascular disease. Studies have shown that TAM can lower LDL and total cholesterol levels but increase the risk of stroke and venous thrombosis. The results of current studies on the effects of aromatase inhibitors on lipid levels in breast cancer patients are controversial. the results of the ATAC study showed that the difference in the incidence of myocardial infarction between patients in the anastrozole and TAM groups was not statistically significant, but the incidence of cerebrovascular accidents was lower in the anastrozole group than in the TAM group. in the BIG 1-98 study, the incidence of hypercholesterolemia was twice as high in patients in the letrozole group as in the TAM group, and the thrombosis In the BIG 1-98 study, the incidence of hypercholesterolemia was twice as high in the letrozole group as in the TAM group, and the incidence of thrombosis was lower than in the TAM group. Further studies are needed regarding the effects of aromatase inhibitors on the cardiovascular system and lipid metabolism. The treatment is mainly to test the patients’ blood pressure and lipid indexes, and to communicate with cardiovascular specialists in time to deal with related symptoms when abnormalities occur. Conclusion Since breast cancer patients need long-term endocrine therapy after surgery, sufficient attention should be paid to the adverse reactions caused by it. Doctors should inform patients of the possible adverse reactions, and patients should also closely observe the adverse reactions in post-discharge treatment and communicate with doctors in a timely manner, so as not to affect the medication compliance due to poor communication and lead to tumor recurrence. Only by paying sufficient attention to the adverse effects of long-term endocrine therapy and scientific management can breast cancer patients get a longer and better life.