IOncology

Histone deacetylases (HDACs) are histone-modifying enzymes that play a key role in regulating epigenetic changes, and they are closely linked to the development and drug resistance of breast cancer. HDAC inhibitors (HDACis) can selectively modulate epigenetic features to control tumor cell proliferation, regulate the cell cycle, and repair DNA damage. As a representative class of epigenetically targeted anti-cancer therapies, HDACis are also recommended by Chinese guidelines as an important treatment option for patients with HR+/HER2- advanced breast cancer who have developed resistance to endocrine therapy. We invited Dr. Qingyuan Zhang from Harbin Medical University Cancer Hospital to share her insights into the current treatment landscape of HR+/HER2- advanced breast cancer and to further explore therapeutic options for patients facing endocrine resistance.

The normalization of epigenetic regulation has emerged as a promising therapeutic strategy in oncology. In hormone receptor-positive (HR⁺) breast cancer, the highly selective HDAC inhibitor (HDACi) entinostat has shown the ability to induce cell cycle arrest and apoptosis in multidrug-resistant tumor cells, addressing resistance to endocrine and targeted therapies at the mechanistic level. Moreover, a large phase III clinical trial has demonstrated entinostat’s survival benefit and safety profile in patients with HR⁺ advanced breast cancer previously treated with CDK4/6 inhibitors. Its weekly dosing regimen also offers a clear advantage in treatment adherence. Dr. Wenming Cao of Zhejiang Cancer Hospital provides a mechanistic perspective on the therapeutic advantages of HDACi entinostat in HR⁺ breast cancer.

Whether anthracyclines are essential in the neoadjuvant chemotherapy of HER2-positive breast cancer remains a long-debated question. The BCIRG-006 study suggested that anthracycline-containing and anthracycline-free regimens yielded numerically comparable survival outcomes, while the anthracycline-free TCbH regimen demonstrated a lower incidence of congestive heart failure and cardiac dysfunction. However, direct head-to-head comparisons between the two strategies are still limited. At the recent 19th St. Gallen Breast Cancer Conference (SGBCC 2025), Prof. Zhaoqing Fan and colleagues of Beijing Cancer Hospital presented a multicenter retrospective study evaluating the efficacy and safety of dual-targeted neoadjuvant therapy with or without anthracyclines in HER2-positive breast cancer. Oncology Frontier invited Professor Fan to interpret the findings.

Breast cancer remains the most frequently diagnosed cancer among women worldwide, and the pursuit of novel therapies continues to command global attention. In the setting of HR+/HER2− advanced breast cancer, the introduction of entinostat, a novel histone deacetylase inhibitor (HDACi), marks a significant therapeutic advancement. With a distinctive mechanism of action, entinostat not only extends overall survival (OS) but also demonstrates a favorable safety profile. Its innovative once-weekly dosing schedule enhances treatment convenience and patient adherence. When combined with an aromatase inhibitor, entinostat opens a new chapter in second-line management for patients progressing after CDK4/6 inhibitors, pushing breast cancer treatment toward a more personalized and precision-based era.

As treatment options for hormone receptor-positive (HR⁺) breast cancer continue to diversify—from chemotherapy and endocrine therapy to targeted treatments—survival outcomes are improving. However, alongside extended survival, maintaining quality of life (QoL) and enabling patients to return to everyday life have become equally vital goals. Entinostat, a novel histone deacetylase inhibitor (HDACi), stands out with its well-tolerated safety profile and convenient dosing regimen. By enhancing both survival and QoL, it provides new therapeutic possibilities for HR⁺ breast cancer patients. Dr. Jun Cao from Fudan University Shanghai Cancer Center shares insights into managing QoL in the chronic disease era and highlights the clinical advantages of entinostat.

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…