Oral SERD, a Novel Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer

Simple Summary Breast cancer is a common type of cancer among women. One type, estrogen receptor-positive (ER+), is treated with endocrine therapies. However, some patients develop resistance to these therapies, which is a challenge. Scientists have developed second-generation drugs called selective estrogen receptor degraders (SERDs) that can overcome the limitations of the existing treatment. These drugs are taken orally, which is more convenient for patients. SERDS are important because they offer a more effective and less invasive treatment option for patients with ER+ breast cancer who develop resistance to endocrine therapies. Several oral SERDs are currently in clinical trials, which means they are being tested on patients. If they are proven effective, they could become a standard treatment for ER+ breast cancer in the future.Abstract Breast cancer is the most common cancer among women worldwide, and estrogen receptor-positive (ER+) breast cancer accounts for a significant proportion of cases. While various treatments are available, endocrine therapies are often the first-line treatment for this type of breast cancer. However, the development of drug resistance poses a significant challenge in managing this disease. ESR1 mutations have been identified as a common mechanism of endocrine therapy resistance in ER+ breast cancer. The first-generation selective estrogen receptor degrader (SERD) fulvestrant has shown some activity against ESR1 mutant tumors. However, due to its poor bioavailability and need for intramuscular injection, it may not be the optimal therapy for patients. Second-generation SERDs were developed to overcome these limitations. These newer drugs have improved oral bioavailability and pharmacokinetics, making them more convenient and effective for patients. Several oral SERDs are now in phase III trials for early and advanced ER+ breast cancer. This review summarizes the background of oral SERD development, the current status, and future perspectives.