Recent Developments in the Therapeutic Landscape of Advanced or Metastatic Hormone Receptor-Positive Breast Cancer

Sep 28, 2026

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Hormone receptor–positive (HR+) breast cancer is the most commonly diagnosed subtype and often shows an indolent natural course with favorable prognosis compared with HER2-positive and triple-negative disease. HR+ tumors rely on steroid hormone signaling, making endocrine therapy central to treatment. Recent progress includes cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy, plus additional nonhormonal targeted agents such as mTOR, PI3K, PARP inhibitors, antibody-drug conjugates, and immunotherapeutic approaches. This review synthesizes current regimens and emerging therapies to guide future research.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Hormone receptor–positive disease overview

Endocrine therapy and emerging nonhormonal targets

Endocrine Therapy Plus CDK4/6 Inhibitors as First-Line Treatment

Classification of endocrine therapy options

Rationale for combination approaches

pISSN 1598-2998, eISSN 2005-9256 | [https://doi.org/10.4143/crt.2023.846](https://doi.org/10.4143/crt.2023.846) Cancer Res Treat. 2023;55(4):1065-1076

Review Article
Recent Developments in the Therapeutic Landscape of Advanced or Metastatic Hormone Receptor–Positive Breast Cancer
Eunice Yoojin Lee1 , Dae-Won Lee2,3,4,5 , Kyung-Hun Lee2,3,4 , Seock-Ah Im2,3,4,5
1Department of Medicine, University of California San Francisco, San Francisco, CA, USA, 2Cancer Research Institute, Seoul National University, Seoul, 3Translational Medicine, Seoul National University College of Medicine, Seoul, 4Department of Internal Medicine, Seoul National University Hospital, Seoul, 5Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea | | | --- | --- | | 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.
Key words Breast neoplasms, Endocrine therapy, Hormone receptor positive, CDK4/6 inhibitor | | | Introduction | also its dependence on estrogen signaling, which is targeted with endocrine therapy agents such as selective ER modu- | | Breast cancer is the most commonly diagnosed cancer worldwide. It is a leading cause of death among women worldwide, with an estimated 2.3 million new cases each | lators (SERMs), aromatase inhibitors (AIs), and selective ERdegraders (SERDs) [5] .
While endocrine therapy continues to be a mainstay of | | year and accounting for over 680,000 deaths in 2020 [1] . | treatment for HR+ breast cancer, the discovery of additional | | Breast cancer is not a single disease entity. Microarray- | nonhormonal molecular targets—namely cyclin-depend- | | based gene expression profiling has identified four intrinsic | ent kinase 4/6 (CDK4/6), mammalian target of rapamycin | | subtypes of breast cancer, which include luminal A, luminal | (mTOR), protein kinase B (also known as Akt), and phos- | | B, human epidermal growth factor protein 2 (HER2)–over- | phatidylinositol 3-kinase (PI3K)—and their translation into | | expression, and triple-negative breast cancer (TNBC) [2] . | novel therapeutic agents have further improved patient out- | | Each subtype also corresponds to a distinct histopathologi- | comes. Despite these milestones, advanced HR+ breast can- | | cal profile based on the expression of hallmark biomarkers, | cer remains an incurable condition, often with mechanisms | | namely the hormone receptors (HR) for estrogen (ER) or | independent of hormonal signaling that contribute to recur- | | progesterone, HER2, and the cell proliferation marker Ki67 . | rence, therapeutic resistance, and/or metastasis, underscor- | | Briefly, luminal A tumors are HR+, HER2–, and Ki67-low; | ing the need for further translational research in this realm. | | luminal B tumors are further subdivided into HR+/HER2–/ | In this review, we will discuss the curr

FAQs

Why is endocrine therapy considered the main treatment for advanced HR+ breast cancer?

HR+ tumors depend on steroid hormone signaling, and endocrine therapy targets estrogen receptor–driven pathways, making it the primary option.

How have CDK4/6 inhibitors improved outcomes in advanced HR+ breast cancer?

The review notes that cyclin-dependent kinase 4/6 inhibitors, used synergistically with endocrine therapy, have dramatically improved treatment outcomes.

What other nonhormonal therapeutic agents expand treatment options for HR+ breast cancer?

Additional agents include targeted therapies against mTOR and PI3K signaling, PARP inhibitors, antibody-drug conjugates, and immunotherapeutic agents.

Sep 28, 2026

Uploaded by Grenda