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Review Article
Recent Developments in the Therapeutic Landscape of Advanced or Metastatic Hormone Receptor–Positive Breast Cancer
Eunice Yoojin Lee, Dae-Won Lee, Kyung-Hun Lee, Seock-Ah Im
Cancer Res Treat. 2023;55(4):1065-1076.   Published online October 5, 2023
DOI: https://doi.org/10.4143/crt.2023.846
AbstractAbstract PDFPubReaderePub
Hormone receptor–positive (HR+) disease is the most frequently diagnosed subtype of breast cancer. Among tumor subtypes, natural course of HR+ breast cancer is indolent with favorable prognosis compared to other subtypes such as human epidermal growth factor protein 2–positive disease and triple-negative disease. HR+ tumors are dependent on steroid hormone signaling and endocrine therapy is the main treatment option. Recently, the discovery of cyclin-dependent kinase 4/6 inhibitors and their synergistic effects with endocrine therapy has dramatically improved treatment outcome of advanced HR+ breast cancer. The demonstrated efficacy of additional nonhormonal agents, such as targeted therapy against mammalian target of rapamycin and phosphatidylinositol 3-kinase signaling, poly(ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and immunotherapeutic agents have further expanded the available therapeutic options. This article reviews the latest advancements in the treatment of HR+ breast cancer, and in doing so discusses not only the development of currently available treatment regimens but also emerging therapies that invite future research opportunities in the field.

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  • Breast Cancer and Tumor Microenvironment: The Crucial Role of Immune Cells
    Tânia Moura, Paula Laranjeira, Olga Caramelo, Ana M. Gil, Artur Paiva
    Current Oncology.2025; 32(3): 143.     CrossRef
  • Metastasiertes hormonrezeptorpositives Mammakarzinom – die Qual der Wahl
    Marion T. van Mackelenbergh, Michael Friedrich, Nicolai Maass
    Die Gynäkologie.2025;[Epub]     CrossRef
  • Therapies for the Treatment of Advanced/Metastatic Estrogen Receptor-Positive Breast Cancer: Current Situation and Future Directions
    Rohan Kalyan Rej, Joyeeta Roy, Srinivasa Rao Allu
    Cancers.2024; 16(3): 552.     CrossRef
  • 4,309 View
  • 248 Download
  • 2 Web of Science
  • 3 Crossref
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Original Articles
Breast cancer
Clinical Evidence of Chemotherapy or Endocrine Therapy Maintenance in Patients with Metastatic Breast Cancer: Meta-Analysis of Randomized Clinical Trials and Propensity Score Matching of Multicenter Cohort Study
Wei Ren, Yunfang Yu, Huangming Hong, Ying Wang, Quanlong Gao, Yongjian Chen, Peixian Chen, Jianli Zhao, Qiyun Ou, Dagui Lin, Tuping Fu, Yujie Tan, Chenchen Li, Xinxin Xie, Guolin Ye, Jun Tang, Herui Yao
Cancer Res Treat. 2022;54(4):1038-1052.   Published online February 4, 2022
DOI: https://doi.org/10.4143/crt.2021.698
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in metastatic breast cancer (MBC) patients.
Materials and Methods
The meta-analysis of randomized clinical trials (RCTs) and propensity score matching of multicenter cohort study evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. This study is registered with PROSPERO: CRD42017071858 and ClinicalTrials.gov: NCT04258163.
Results
A total of 2,867 patients from 15 RCTs and 760 patients from multicenter cohort were included. The results from meta-analysis showed that chemotherapy maintenance improved progression-free survival (PFS) (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.54 to 0.73; p < 0.001; moderate-quality evidence) and overall survival (OS) (HR, 0.87; 95% CI 0.78 to 0.97; p=0.016; high-quality evidence) than observation. In the cohort study, for hormone receptor–positive MBC patients, chemotherapy maintenance improved PFS (HR, 0.67; 95% CI, 0.52 to 0.85; p < 0.001) and OS (HR, 0.55; 95% CI 0.42 to 0.73; p < 0.001) compared with observation, and endocrine therapy maintenance also improved PFS (HR, 0.65; 95% CI, 0.53 to 0.80; p < 0.001) and OS (HR, 0.55; 95% CI, 0.44 to 0.69; p < 0.001). There were no differences between chemotherapy and endocrine therapy maintenance in PFS and OS (all p > 0.05). Regardless of the continuum or switch maintenance therapy, showed prolonged survival in MBC patients who were response to first-line treatment.
Conclusion
This study provided evidences for survival benefits of chemotherapy and endocrine therapy maintenance in MBC patients, and there was no difference efficacy between chemotherapy and endocrine therapy maintenance for hormone receptor–positive patients.

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  • 6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7)
    Fatima Cardoso, Shani Paluch-Shimon, Eva Schumacher-Wulf, Leonor Matos, Karen Gelmon, Matti S. Aapro, Jyoti Bajpai, Carlos H. Barrios, Jonas Bergh, Elizabeth Bergsten-Nordström, Laura Biganzoli, Maria João Cardoso, Lisa A. Carey, Mariana Chavez-MacGregor,
    The Breast.2024; 76: 103756.     CrossRef
  • Maintenance endocrine therapy plus bevacizumab for advanced or metastatic breast cancer
    Stanislas Quesada, William Jacot
    The Lancet Oncology.2022; 23(5): 557.     CrossRef
  • 6,035 View
  • 162 Download
  • 2 Web of Science
  • 2 Crossref
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Breast Cancer
Implications of Tamoxifen Resistance in Palbociclib Efficacy for Patients with Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Subgroup Analyses of KCSG-BR15-10 (YoungPEARL)
Jiyun Lee, Seock-Ah Im, Gun Min Kim, Kyung Hae Jung, Seok Yun Kang, In Hae Park, Jee Hyun Kim, Hee Kyung Ahn, Yeon Hee Park
Cancer Res Treat. 2021;53(3):695-702.   Published online December 17, 2020
DOI: https://doi.org/10.4143/crt.2020.1246
AbstractAbstract PDFPubReaderePub
Purpose
YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC.
Results
In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.

Citations

Citations to this article as recorded by  
  • Palbociclib plus endocrine therapy in hormone receptor-positive and HER2 negative metastatic breast cancer: a multicenter real-world study in the northwest of China
    Jiao Yang, Bing Zhao, Xiaoling Ling, Donghui Li, Jiuda Zhao, Yonggang Lv, Guangxi Wang, Xinlan Liu, Nanlin Li, Jin Yang
    BMC Cancer.2023;[Epub]     CrossRef
  • 7,388 View
  • 278 Download
  • 2 Web of Science
  • 1 Crossref
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