Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 117-125 http://medscipublisher.com/index.php/cge 118 2 Review of Endocrine Therapy for Breast Cancer 2.1 Commonly used endocrine therapy drugs and their mechanisms of action Selective estrogen receptor modulators (SERMs), such as tamoxifen, work by competing for positions with estrogen receptors, thereby preventing estrogen from causing breast cancer cells to grow continuously. Aromatase inhibitors (AIs), such as anastrozole and letrozole, can inhibit aromatase, reduce the production of estrogen in the body, and prevent those hormone-dependent tumors from obtaining "nutrients" (Sharma et al., 2021). Selective estrogen receptor degraders (serd), taking flvovestine as an example, bind to estrogen receptors and then promote receptor decomposition, more thoroughly cutting off the signal of estrogen transmission (Fan et al., 2015; Rani et al., 2019; Sahin et al., 2021). These drugs "target" the estrogen receptor pathway in different ways, providing multiple options for preventing estrogen-stimulated tumor growth (Fan et al., 2015; Rani et al., 2019). Which specific medicine to use generally depends on whether the patient has reached menopause, what treatments they have received before, and their specific condition. Currently, a new generation of SERDs and new drugs such as endoplasmic reticulum proteolytic targeted chimeras (PROTACs) are under development, with the aim of addressing drug resistance and enhancing therapeutic efficacy (Sahin et al., 2021). 2.2 Indications: patient population and treatment timing Most breast cancer patients are positive for hormone receptors, and such patients are suitable for endocrine therapy (Lani et al., 2019; Sharma et al., 2021). For early-stage breast cancer, endocrine therapy is usually performed after surgery to reduce the risk of cancer recurrence and improve the survival rate of patients (Fan et al., 2015). If breast cancer has metastasized, endocrine therapy is still the preferred treatment method for most patients, and it is often used in combination with targeted drugs to delay the progression of the disease (Rani et al., 2019; Hartkopf et al., 2020). When to start endocrine therapy and which drugs to choose should comprehensively consider which stage the cancer has reached, the menopause status of the patient, and the previous treatment experience (Fan et al., 2015). For patients with early-stage breast cancer, treatment can be scheduled after surgery or radiotherapy, and sometimes before or after chemotherapy (Li, 2024). For patients with metastatic breast cancer, endocrine therapy is generally continued until drug resistance occurs. At this point, it is necessary to consider combining other treatment methods or switching to other drugs (Rani et al., 2019; Hartkopf et al., 2020; Sahin et al., 2021). 2.3 Evaluation of therapeutic effect and prognostic factors The effect of endocrine therapy has been verified and it can significantly reduce the recurrence rate and mortality rate of patients with hormone receptor-positive breast cancer (Lani et al., 2019). However, some patients have no effect at the beginning of the treatment, and some patients develop drug resistance after a period of treatment. All these will affect the long-term treatment effect. Therefore, it is necessary to constantly observe the treatment response and adjust the treatment plan in a timely manner (Fan et al., 2015; Sahin et al., 2021; Sharma et al., 2021; Tanwar et al., 2025). There are many factors affecting the therapeutic effect, such as the conditions of estrogen receptor (ER) and progesterone receptor (PR) in the tumor, the expression level of HER2 protein, whether there are gene mutations (like ESR1 mutations), and whether there are changes in some key signaling pathways (Rani et al., 2019; Hartkopf et al., 2020; Sahin et al., 2021). Clinical trials and comprehensive analysis have found that on the basis of endocrine therapy, combined treatment with targeted drugs such as CDK4/6, mTOR or PI3K inhibitors can prolong the time for patients with endocrine resistance not to have disease deterioration and improve the overall survival rate (Hartkopf et al., 2020; Sahin et al., 2021; Tanwar et al., 2025). Finding biomarkers related to drug resistance and clarifying the changes at the molecular level are crucial for optimizing the treatment plan and improving the therapeutic effect of patients (Rani et al., 2019). 3 Classification of Endocrine Resistance 3.1 Primary drug resistance: ineffective from the beginning of treatment Primary endocrine resistance refers to hormone receptor-positive breast cancer patients who have no response to
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