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Systemic therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative early stage and metastatic breast cancer. ​

Literature Information ​

DOI10.3322/caac.21777
PMID36939293
JournalCA: a cancer journal for clinicians
Impact Factor232.4
JCR QuartileQ1
Publication Year2023
Times Cited70
Keywordsbreast neoplasms, clinical trials, hormone receptor-positive, hormone therapy, human epidermal growth factor receptor 2 (HER2)-negative breast cancer
Literature TypeJournal Article, Review
ISSN0007-9235
Pages480-515
Issue73(5)
AuthorsLaura A Huppert, Ozge Gumusay, Dame Idossa, Hope S Rugo

TL;DR ​

This review examines hormone receptor-positive and HER2-negative breast cancer, which constitutes 65%-70% of cases and primarily relies on endocrine therapy, particularly in combination with cyclin-dependent kinase 4/6 inhibitors, to enhance survival outcomes. The authors highlight the importance of understanding the disease's molecular characteristics and emerging treatment strategies to optimize therapy sequences and improve patient outcomes while reducing toxicity.

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breast neoplasms · clinical trials · hormone receptor-positive · hormone therapy · human epidermal growth factor receptor 2 (HER2)-negative breast cancer

Abstract ​

Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is defined by the presence of the estrogen receptor and/or the progesterone receptor and the absence of HER2 gene amplification. HR-positive/HER2-negative breast cancer accounts for 65%-70% of all breast cancers, and incidence increases with increasing age. Treatment varies by stage, and endocrine therapy is the mainstay of treatment in both early stage and late-stage disease. Combinations with cyclin-dependent kinase 4/6 inhibitors have reduced distant recurrence in the early stage setting and improved overall survival in the metastatic setting. Chemotherapy is used based on stage and tumor biology in the early stage setting and after endocrine resistance for advanced disease. New therapies, including novel endocrine agents and antibody-drug conjugates, are now changing the treatment landscape. With the availability of new treatment options, it is important to define the optimal sequence of treatment to maximize clinical benefit while minimizing toxicity. In this review, the authors first discuss the pathologic and molecular features of HR-positive/HER2-negative breast cancer and mechanisms of endocrine resistance. Then, they discuss current and emerging therapies for both early stage and metastatic HR-positive/HER2-negative breast cancer, including treatment algorithms based on current data.

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Primary Questions Addressed ​

  1. What are the latest advancements in novel endocrine agents for treating HR-positive/HER2-negative breast cancer?
  2. How do the mechanisms of endocrine resistance impact the choice of systemic therapy in metastatic settings?
  3. What are the comparative benefits of combining cyclin-dependent kinase 4/6 inhibitors with traditional endocrine therapies?
  4. How do treatment algorithms differ between early stage and metastatic HR-positive/HER2-negative breast cancer?
  5. What role do patient-specific factors play in determining the optimal sequence of systemic therapies for HR-positive/HER2-negative breast cancer?

Key Findings ​

1. Research Background and Purpose ​

The study focuses on hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer, which constitutes a significant proportion (65%-70%) of all breast cancer cases. This subtype is characterized by the presence of estrogen and/or progesterone receptors, coupled with the absence of HER2 gene amplification. The incidence of this cancer subtype increases with age, necessitating effective treatment strategies. The primary objective of the review is to evaluate the current and emerging systemic therapies for both early stage and metastatic HR-positive/HER2-negative breast cancer, with a focus on optimizing treatment sequences to enhance clinical outcomes while reducing toxicity.

2. Main Methods and Findings ​

The authors conducted a comprehensive review of the pathological and molecular characteristics of HR-positive/HER2-negative breast cancer, particularly emphasizing mechanisms of endocrine resistance that often complicate treatment. They analyzed current treatment protocols, which predominantly feature endocrine therapy as the mainstay for both early and late-stage disease. The review highlights the efficacy of combining endocrine therapy with cyclin-dependent kinase 4/6 inhibitors, which have shown to significantly decrease the risk of distant recurrence in early-stage cases and improve overall survival in metastatic scenarios. Additionally, the review discusses the role of chemotherapy, which is tailored based on tumor biology and stage, particularly in cases of endocrine resistance. The emergence of novel endocrine agents and antibody-drug conjugates marks a pivotal shift in the treatment landscape, offering new avenues for managing this cancer subtype.

3. Core Conclusions ​

The review concludes that while endocrine therapy remains central to the treatment of HR-positive/HER2-negative breast cancer, the integration of targeted therapies, such as CDK4/6 inhibitors and novel agents, is transforming clinical practice. The authors underscore the necessity of understanding the mechanisms behind endocrine resistance to refine treatment approaches. Effective treatment algorithms are essential to ensure that patients receive personalized therapy that maximizes therapeutic benefits while minimizing adverse effects.

4. Research Significance and Impact ​

This review is significant as it provides a thorough overview of the evolving treatment landscape for HR-positive/HER2-negative breast cancer, highlighting the importance of personalized medicine. By synthesizing current evidence and emerging therapies, the study informs clinicians about potential strategies to enhance patient outcomes. The insights gained from this research could influence future clinical guidelines and improve treatment protocols, ultimately contributing to increased survival rates and quality of life for patients diagnosed with this prevalent breast cancer subtype. Furthermore, it sets the stage for future research aimed at overcoming endocrine resistance and developing innovative therapeutic modalities.

Literatures Citing This Work ​

  1. 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 research and treatment (2023)
  2. Decoding TROP2 in breast cancer: significance, clinical implications, and therapeutic advancements. - Liqin Yao;Junfeng Chen;Wenxue Ma - Frontiers in oncology (2023)
  3. Updated Review Article: Cyclin-Dependent Kinase 4/6 Inhibitor Impact, FDA Approval, and Resistance Pathways. - Rodney J Hunter;Jooyoung Park;Kristen J Asprer;Andrew H Doan - The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians (2023)
  4. STAT4 facilitates PD-L1 level via IL-12R/JAK2/STAT3 axis and predicts immunotherapy response in breast cancer. - Jianbo Zhou;Feng Wan;Li Wang;Cheng Peng;Ruizhen Huang;Fu Peng - MedComm (2023)
  5. HTRA1 expression is associated with immune-cell infiltration and survival in breast cancer. - Dawei Zhao;Wanfeng Li;Yan Wang;Gengyue Zhang;Xinhua Bai;Hong Yu - Translational cancer research (2023)
  6. A network meta-analysis of efficacy and safety for first-line and second/further-line therapies in postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer. - Hanqiao Shao;Mingye Zhao;Ai-Jia Guan;Taihang Shao;Dachuang Zhou;Guo Yu;Wenxi Tang - BMC medicine (2024)
  7. The prognostic implications and tumor-suppressive functions of CYR61 in estrogen receptor-positive breast cancer. - Cheng Zhang;Zhihua Li;Kaiheng Hu;Yifei Ren;Haoran Zhang;Yuankang Zhao;Wenjing Wei;Shuo Tu;Xiaohua Yan - Frontiers in immunology (2023)
  8. Edaravone: A Novel Possible Drug for Cancer Treatment? - Elisa Duranti;Nicoletta Cordani;Chiara Villa - International journal of molecular sciences (2024)
  9. 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)
  10. A real-world clinicopathological model for predicting pathological complete response to neoadjuvant chemotherapy in breast cancer. - Shan Fang;Wenjie Xia;Haibo Zhang;Chao Ni;Jun Wu;Qiuping Mo;Mengjie Jiang;Dandan Guan;Hongjun Yuan;Wuzhen Chen - Frontiers in oncology (2024)

... (60 more literatures)

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