In recent times, tamoxifen has been hard to find all over the country. Many breast cancer patients are asking: Can I stop taking tamoxifen if I can’t buy it? Can I switch to other drugs? How should premenopausal breast cancer patients use selective estrogen receptor modulators? Here, we will answer your questions about these hot issues. 1. Can I stop taking tamoxifen if I cannot buy it? For hormone receptor positive breast cancer patients, it is not recommended to discontinue endocrine therapy drugs without authorization. Postoperative endocrine therapy for premenopausal hormone receptor-positive breast cancer patients can reduce local recurrence and improve breast cancer survival. The duration of selective estrogen receptor modulator use is determined by the risk of breast cancer recurrence, usually 5 to 10 years. Discontinuing endocrine therapy drugs in the middle of treatment can put patients at increased risk of cancer recurrence and death. Therefore, breast cancer patients should never discontinue endocrine drugs because they have recovered better or because they have been treated for too long. If tamoxifen is not available, consider replacing it with other drugs. 2. What is the difference between tamoxifen and toremifene? Both tamoxifen and toremifene are selective estrogen receptor modulators that block the growth of breast cancer cells by regulating endogenous estrogen for the purpose of treating breast cancer. Tamoxifen behaves as an antagonist in the breast tissue but as an agonist in the uterus. Long-term use may lead to endometrial thickening, endometrial hyperplasia, endometrial cancer, ovarian cysts, and other reproductive system adverse effects. Toremifene is a derivative of tamoxifen and its structure and mechanism of action are very similar to those of tamoxifen. It is optimized on the structure of tamoxifen by replacing a hydrogen atom on the ethane group of tamoxifen by a chlorine atom, which makes the overall structure more stable and less likely to form DNA adducts (affecting the repair of damaged DNA) and reduces the occurrence of adverse reactions. Toremifene, through structural optimization, not only has stronger tumor inhibitory activity, but also has less impact on the endometrium. According to the pharmacokinetic analysis of tamoxifen, tamoxifen relies on a metabolic enzyme called CYP2D6 for its efficacy. Toremifene, on the other hand, is mainly metabolized by CYP3A4 enzyme and is less affected by CYP2D6 metabolizing enzyme. Available clinical data show that toremifene is comparable to tamoxifen in terms of efficacy in treating early-stage breast cancer and less severe than tamoxifen in terms of adverse drug effects. According to the “Chinese Expert Consensus on the Safe Management of Endometrium Associated with Selective Estrogen Receptor Modulator Therapy in Breast Cancer Patients (Version 2021)”, it is recommended that premenopausal asymptomatic women treated with selective estrogen receptor modulators who have endometrial thickening (endometrial thickness >15mm) on ultrasound may continue to take the drug for observation or switch to a drug that has less effect on the endometrium. medication, such as toremifene, and to increase the frequency of follow-up visits. In addition to gynecological aspects, patients may develop fatty liver and dyslipidemia with long-term use of tamoxifen. According to the recommendation of “Chinese Expert Consensus on Long-term Management of Adjuvant Therapy with Selective Estrogen Receptor Modulators in Early Stage Hormone Receptor Positive Breast Cancer Patients”, choosing toremifene can better reduce the side effects of liver damage and dyslipidemia. Toremifene treatment can be chosen for patients who have contraindications to tamoxifen use, have significant adverse effects from taking tamoxifen, or whose CYP2D6 gene test does not recommend tamoxifen use. Although toremifene is mainly suitable for endocrine treatment of postmenopausal breast cancer patients, it can be used for endocrine treatment of some premenopausal breast cancer patients with good clinical results. 3. How to use selective estrogen receptor modulators in postoperative adjuvant endocrine therapy for premenopausal breast cancer? For postoperative breast cancer patients with ER and/or PR positive hormone receptors, the use of adjuvant endocrine therapy can reduce tumor recurrence and improve overall survival. Among them, the most commonly used are anti-estrogenic drugs, which are a class of compounds with inhibitory or attenuating estrogenic effects. Commonly used drugs include tamoxifen, toremifene, clomiphene and raloxifene, which can selectively modulate ER activity, but different drugs play different roles on different sites of ER. There are usually three treatment options for premenopausal hormone receptor positive breast cancer: selective estrogen receptor modulators (e.g. tamoxifen), ovarian function inhibition plus selective estrogen receptor modulators and ovarian function inhibition plus aromatase inhibitors. In case of intraductal carcinoma and early premenopausal hormone receptor positive patients, selective estrogen receptor modulators are recommended; for patients with high risk of recurrence, regimens such as endocrine drugs combined with CDK4/6 inhibitors can also be chosen; after taking anti-estrogenic drugs for 5 years, patients are still in premenopausal status, and some patients such as those at high risk of recurrence can be considered for extension up to 10 years. In case of postmenopausal hormone receptor positive patients, aromatase inhibitors are the treatment of choice. In conclusion, breast cancer is a chronic disease, and the choice of endocrine therapy drugs depends on several aspects, including the therapeutic effect of the drug, the degree of adverse effects and the price of the drug, and also depends on the patient’s disease grading and staging and the assessment of the risk of recurrence, only what is suitable for you is the best. Only if the doctor fully understands the patient’s medical history and the patient gives positive feedback on individual differences, can we know ourselves and each other and never lose a battle.