Evolving First-Line Endocrine Therapy in HR+/HER2− Metastatic Breast Cancer: CDK4/6 Inhibition, Biomarker-Guided Strategies and Emerging Therapeutic Paradigms.
Simple Summary: Hormone receptor-positive, HER2-negative metastatic breast cancer, the most common type of advanced breast cancer, depends on estrogen to grow. Treatments that block this hormone remain the basis of care, especially when combined with newer drugs (CDK4/6 inhibitors) that slow cancer...
| Publicado en: | Current Oncology Vol. 33; no. 7; pp. 421 - 442 |
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| Autores principales: | , |
| Formato: | Journal Article |
| Publicado: |
MDPI
Jul2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=195807453&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 195807453 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 11980052 5EKK jtl: Current Oncology issn: 11980052 maglogo: N pubinfo: dt: Jul2026 vid: 33 iid: 7 pid: 97109 pub: MDPI artinfo: ui: 195807453 10.3390/curroncol33070421 195807453 ppf: 421 ppct: 21 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Evolving First-Line Endocrine Therapy in HR+/HER2− Metastatic Breast Cancer: CDK4/6 Inhibition, Biomarker-Guided Strategies and Emerging Therapeutic Paradigms. aug: au: Abdel-Razeq, Hikmat Sharaf, Baha affil: Section of Hematology and Medical Oncology, Department of Internal Medicine, King Hussein Cancer Center, Amman 11941, Jordan sug: ab: Simple Summary: Hormone receptor-positive, HER2-negative metastatic breast cancer, the most common type of advanced breast cancer, depends on estrogen to grow. Treatments that block this hormone remain the basis of care, especially when combined with newer drugs (CDK4/6 inhibitors) that slow cancer cell division and significantly prolong survival. However, most cancers eventually become resistant to this therapy. Recent advances are helping physicians stay ahead of this resistance. Blood-based tests (liquid biopsies) can now detect early genetic changes in the tumor, allowing treatment to be adjusted before the disease worsens. In addition, targeted therapies can be added for patients with specific mutations (such as PIK3CA), further improving outcomes. Altogether, care is moving toward a more personalized and adaptive approach, aiming to extend disease control, delay the need for chemotherapy, and maintain quality of life. Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) metastatic breast cancer (MBC) is the most prevalent subtype of advanced breast cancer and is predominantly driven by estrogen receptor (ER) signaling. Endocrine therapy (ET) has become the backbone of first-line treatment; however, both intrinsic and acquired resistance limit long-term disease control. The introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has fundamentally reshaped the therapeutic landscape even in subsets of patients with aggressive or symptomatic visceral metastatic disease. Advances in molecular profiling have also enabled more precise, adaptive therapy. Circulating tumor DNA (ctDNA)-based liquid biopsy now allows real-time detection of emerging resistance mutations, particularly in ESR1. Additionally, patients with PIK3CA-mutated tumors who had progressed on or within 12 months of completing adjuvant ET and had no prior systemic therapy for metastatic disease had better treatment outcomes when treated with the PI3K inhibitor inavolisib in combination with palbociclib and fulvestrant. Together, these developments mark a shift from fixed treatment sequencing toward a more dynamic, biomarker-driven approach in first-line HR+/HER2– MBC. Integration of CDK4/6 inhibitors with next-generation endocrine agents and liquid biopsy-guided therapy offers the potential to delay resistance, improve survival outcomes, and individualize treatment. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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