Hormone receptor-positive (HR+) breast cancer accounts for approximately 70% of all breast cancer cases and remains the most prevalent subtype. While endocrine therapy continues to serve as the cornerstone of HR+ breast cancer treatment, and CDK4/6 inhibitors (CDK4/6i) have become standard in both early and advanced settings, resistance to therapy remains a formidable clinical challenge. With growing insights into resistance mechanisms, histone deacetylase inhibitors (HDACi) have emerged as a promising strategy for reversing endocrine resistance through epigenetic modulation. In this article, Dr. Peifen Fu of The First Affiliated Hospital, Zhejiang University School of Medicine, discusses the underlying biology of endocrine resistance in advanced HR+ breast cancer and highlights the therapeutic potential of the novel HDACi, entinostat.

Breast cancer remains one of the leading malignancies threatening women’s health worldwide. Among its various subtypes, hormone receptor-positive (HR⁺) breast cancer is the most prevalent, comprising about 70% of all cases. While the advent of CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) has become the gold standard for first-line treatment of HR⁺/HER2⁻ advanced breast cancer (MBC), therapeutic strategies following progression on CDK4/6i remain a considerable challenge. The introduction of the histone deacetylase inhibitor (HDACi) entinostat has brought a new horizon of hope for patients in this therapeutic gap. Recently, entinostat prescriptions were issued across major cities in China, such as Beijing and Guangdong, marking a pivotal moment in the treatment landscape. Oncology Frontier invited Dr. Xiaojia Wang from Zhejiang Cancer Hospital to delve deeper into the current status of HR⁺/HER2⁻ MBC treatment, strategies after CDK4/6i failure, and the efficacy and safety profile of entinostat.

With the continuous advancement of pharmaceutical and medical technologies, novel therapies have steadily extended survival for breast cancer patients. Among them, the combination of CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) has brought transformative improvements in outcomes for patients with hormone receptor-positive/HER2-negative (HR+/HER2−) metastatic breast cancer (MBC). Despite its establishment as the current standard first-line treatment, a significant number of patients still experience disease progression, and therapeutic options after CDK4/6i failure remain limited and without consensus.

Breast cancer remains one of the most prevalent malignancies among women worldwide, and its hormone receptor-positive, HER2-negative (HR+/HER2−) subtype accounts for nearly 70% of all cases. In recent years, the combination of CDK4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) has become the gold standard for first-line treatment in metastatic settings. However, once progression occurs on CDK4/6i-based regimens, the optimal path forward is less clearly defined, presenting a persistent challenge in clinical decision-making.

Hormone receptor-positive (HR⁺) breast cancer accounts for approximately 70% of all breast cancer cases, representing a large population in need of effective treatment strategies. In recent years, first-line treatment with…

As breast cancer continues to rank as the most frequently diagnosed cancer among women worldwide, hormone receptor-positive, HER2-negative (HR+/HER2⁻) disease remains its most common subtype. In recent years, combining CDK4/6…

Breast cancer remains the leading malignancy threatening women’s health worldwide. Among its subtypes, hormone receptor-positive/HER2-negative (HR+/HER2−) breast cancer is the most common and typically has a better prognosis, having now entered the era of chronic disease management. In the context of long-term, whole-course management—often spanning over a decade—the concept of “patient-centered care” has become central to clinical practice. Reducing the frequency of medication through long-acting therapies can significantly improve the patient experience, enhance quality of life, and boost adherence.

Breast cancer is the most common malignancy among women worldwide, with the HR+/HER2- subtype being one of the most prevalent forms. With the rapid advancement of medical technology and the continuous emergence of new therapies, patient survival has significantly improved, bringing hope to many. Recently, the novel oral HDAC inhibitor entinostat received official approval from China’s National Medical Products Administration (NMPA) for use in combination with an aromatase inhibitor (AI) to treat patients with HR+/HER2- locally advanced or metastatic breast cancer who have relapsed or progressed following endocrine therapy. On July 25, the first prescriptions were issued in Guangdong, Guangxi, Beijing, and other provinces in China, marking a major milestone. This significant breakthrough offers a new treatment option for patients with HR+/HER2- advanced breast cancer and is expected to reshape the current therapeutic landscape.