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.Quality of Life: A Priority in the Era of Chronic Disease Management
Breast cancer remains the most commonly diagnosed malignancy among women worldwide. Approximately 70% of all breast cancer cases are HR⁺/HER2⁻, making this the predominant molecular subtype globally¹. These patients typically undergo long-term endocrine therapy and generally have a more favorable prognosis than those with other subtypes.
In China, breast cancer incidence is trending toward younger populations. Historical data indicate that two-thirds of Chinese women diagnosed with breast cancer are premenopausal or perimenopausal². According to the National Cancer Center of China (2004–2015 data), 53% of patients with advanced HR⁺/HER2⁻ breast cancer were premenopausal³. Compared with postmenopausal women, premenopausal patients have a higher proportion of HR⁺ tumors and require longer treatment durations. Over time, the chronic nature of endocrine therapy and its side effects may negatively impact patients’ quality of life.
In 2006, the World Health Organization included malignant tumors in the global chronic disease management framework. In 2015, China followed suit, designating cancer as a key chronic disease in its “Healthy China 2030” blueprint. Given its high incidence, increasing cure rates, and prolonged survival, breast cancer is now viewed as a model for chronic cancer management⁴.
Quality of life is now regarded as a core treatment goal—equally important as extending survival. It encompasses physical well-being, emotional health, and social functioning. In the context of long-term cancer management, healthcare providers and patients alike are focusing more on minimizing treatment burden and improving daily living.
Entinostat: Dual Gains in Efficacy and Tolerability
Thanks to advances in precision medicine and drug development, breast cancer survival has improved significantly. Data from the National Cancer Center show that the five-year survival rate for breast cancer patients in China surpassed 83% in 2015, approaching levels seen in developed countries⁴. While early-stage patients benefit from curative treatment, those with advanced disease continue to face complex challenges.
The widespread use of CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) has markedly improved outcomes in HR⁺ advanced breast cancer. However, resistance to CDK4/6i therapy is becoming increasingly common, and reversible resistance targets remain elusive. As such, there is an urgent need for effective treatment options beyond CDK4/6i⁵.
Entinostat, a next-generation HDACi, has demonstrated promising results in terms of efficacy, safety, and patient tolerability. A Phase 1 trial in Japan first showed the combination of entinostat with exemestane was well tolerated and showed antitumor activity in HR⁺ advanced breast cancer patients⁶. These findings were further confirmed in the pivotal Phase 3 EOC103A3101 trial led by Academician Binghe Xu of the Chinese Academy of Medical Sciences⁷.
According to the study results, entinostat combined with exemestane significantly improved median progression-free survival (PFS) compared with the placebo group (6.32 vs. 3.72 months; HR 0.76). More notably, the median overall survival (OS) reached 38.39 months in the entinostat group—over 9 months longer than the control group—representing a 17% reduction in mortality risk (HR 0.83). This positions entinostat as the only HDACi to date demonstrating a median OS exceeding 38 months in HR⁺ advanced breast cancer.
In terms of safety, the incidence of adverse events in the entinostat group was comparable to that of the placebo group, with the majority of events being mild to moderate. The main causes of treatment discontinuation included neutropenia, elevated γ-glutamyl transferase, and anemia—yet overall, the safety profile of entinostat was deemed manageable.
Weekly Dosing Enhances the Treatment Experience
In April 2024, the National Medical Products Administration (NMPA) officially approved entinostat, an oral HDAC inhibitor, in combination with an aromatase inhibitor for the treatment of HR⁺/HER2⁻ locally advanced or metastatic breast cancer following progression on endocrine therapy. Since then, prescriptions have been issued in several provinces across China.
Entinostat’s pharmacokinetic design offers a significant advantage—its long half-life of 61.9 hours allows for once-weekly oral dosing. This convenient schedule minimizes treatment disruption, reducing medication frequency and enhancing the overall patient experience.
In the context of chronic disease management, especially in breast cancer, medication adherence plays a crucial role in optimizing treatment outcomes. Conventional regimens requiring daily or frequent dosing can impose psychological and logistical burdens, often leading to missed doses or premature treatment discontinuation. The weekly regimen of entinostat directly addresses these challenges. A meta-analysis has shown that high adherence improves health outcomes by as much as 26% compared to low adherence⁹. Entinostat’s weekly dosing is therefore more than a convenience—it contributes directly to improved efficacy and prolonged survival.
Side Effects Are Well-Managed in Clinical Practice
The most frequently observed adverse events with entinostat are hematologic and hepatic in nature. However, these side effects are generally controllable with established clinical protocols:
- Neutropenia can be managed with continued treatment, dose adjustment, or prophylactic administration of granulocyte-colony stimulating factor (G-CSF).
- Thrombocytopenia may be treated symptomatically, and platelet transfusions can be administered if necessary.
- Hepatotoxicity should be monitored using liver function tests and addressed according to the severity of liver enzyme elevations, with treatment interruption and specialist consultation as needed.
A Promising Option for Enhancing Quality of Life
As entinostat becomes more widely integrated into clinical practice, more patients with HR⁺ advanced breast cancer are benefitting from its strong efficacy, manageable safety, and convenient dosing schedule. The reduced need for frequent hospital visits and monitoring lowers treatment burden and allows patients to maintain their daily routines with minimal disruption.
By offering a treatment option that aligns with both clinical goals and patient-centered care, entinostat is helping HR⁺ breast cancer patients not only live longer but also live better. As medical science continues to advance, entinostat represents the type of innovative therapy that brings together survival benefit, safety, and quality of life—a combination that defines the future of breast cancer treatment.
References
¹ Lim, Elgene et al. The natural history of hormone receptor-positive breast cancer. Oncology (Williston Park, N.Y.) vol. 26,8 (2012): 688–94, 696.
² Li, Qiao et al. A nation-wide multicenter 10-year (1999–2008) retrospective study of chemotherapy in Chinese breast cancer patients. Oncotarget vol. 8,44 75864–75873. 22 Mar. 2017. doi:10.18632/oncotarget.16439
³ Li, Yiqun et al. Real world initial palliative treatment patterns and clinical outcomes in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer: A study of the National Cancer Center, China. Breast (Edinburgh, Scotland) vol. 61 (2022): 129–135. doi:10.1016/j.breast.2021.12.017
⁴ 国家肿瘤质控中心乳腺癌专家委员会, 北京乳腺病防治学会健康管理专业委员会. 中国乳腺癌随诊随访与健康管理指南(2022版)[J]. 中华肿瘤杂志, 2022, 44(1):1–28. DOI:10.3760/cma.j.cn112152-20211029-00798.
⁵ 王佳妮, 李青, 徐兵河. 组蛋白去乙酰化酶抑制剂在HR阳性HER-2阴性晚期乳腺癌的研究进展[J]. 中国肿瘤临床, 2023, 50(17): 897–900. doi: 10.12354/j.issn.1000-8179.2023.20230580
⁶ Masuda N, Tamura K, Yasojima H, et al. Phase 1 trial of entinostat as monotherapy and combined with exemestane in Japanese patients with hormone receptor-positive advanced breast cancer. BMC Cancer 2021;21:1269.
⁷ Xu, Binghe et al. Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. Acta Pharm Sin B. 2023;13(5):2250–2258. doi:10.1016/j.apsb.2023.02.001
⁸ 恩替司他说明书. ⁹ DiMatteo, M Robin et al. Patient adherence and medical treatment outcomes: a meta-analysis. Medical care vol. 40,9 (2002): 794–811. doi:10.1097/00005650-200209000-00009
Deputy Chief Physician, Department of Medical Oncology Fudan University Shanghai Cancer Center
- Youth Member, Breast Cancer Committee, Shanghai Anti-Cancer Association
- Member, Clinical Research and Translational Medicine Committee, Antineoplastic Drug Committee, Shanghai Anti-Cancer Association
- Member, Cancer Pain and Supportive Care Committee, Shanghai Anti-Cancer Association
- Member, Breast Disease Committee, Shanghai Medical Association
- Standing Member, International Medical Education Committee, Chinese Medical Education Association
- Member, Oncology Pharmacology Professional Committee, Chinese Society of Biomedical Engineering
- Member, Oncology Nursing Committee, Chinese Medical Education Association
- Member, Breast Cancer Expert Committee, Chinese Medical Doctors Association
- Member, Yangtze River Breast Cancer Group (YBCSG)
- Reviewer, Chinese Journal of Cancer Biotherapy
- Contributor to several authoritative books including Q&A on Difficult Breast Cancer Consultations, Breast Cancer Medical Oncology Therapy, Handbook of Medical Oncology Treatment, and Handbook of Chemotherapy Regimens in Medical Oncology
