Optimizing therapeutic approaches for HR+/HER2- advanced breast cancer: clinical perspectives on biomarkers and treatment strategies post-CDK4/6 inhibitor progression DOI Open Access

J.M. Cejalvo Andujar,

Francisco Ayala de la Peña, Mireia Margelí Vila

et al.

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

This review offers an expert perspective on biomarkers, CDK4/6 inhibitor efficacy, and therapeutic approaches for managing hormone receptor-positive (HR+), human epidermal growth factor receptor-negative (HER2-) advanced breast cancer (ABC), particularly after progression. Key trials have demonstrated that combining inhibitors with endocrine therapy (ET) significantly improves progression-free survival (PFS), median durations ranging from 14.8 to 26.7 months, overall (OS), reaching up 53.7 months. Actionable such as PIK3CA ESR1 mutations, emerged pivotal tools guide second-line treatment decisions, enabling the use of targeted therapies like alpelisib elacestrant emphasizing important role biomarkers in guiding selection therapy. overview aims provide clinicians a practical up-to-date framework inform decisions improve patient care context this challenging disease. Additionally, we emerging novel strategies address difficult clinical landscape.

Language: Английский

Moving toward precision medicine to predict drug sensitivity in patients with metastatic breast cancer DOI Creative Commons
Michele Bottosso,

F. Mosele,

Stefan Michiels

et al.

ESMO Open, Journal Year: 2024, Volume and Issue: 9(3), P. 102247 - 102247

Published: Feb. 23, 2024

Tumor heterogeneity represents a major challenge in breast cancer, being associated with disease progression and treatment resistance. Precision medicine has been extensively applied to dissect tumor and, through deeper molecular understanding of the disease, personalize therapeutic strategies. In last years, technological advances have widely improved cancer biology several trials developed translate these new insights into clinical practice, ultimate aim improving patients' outcomes. era oncology, genomics analyses other methodologies are shaping algorithm care. this manuscript, we review main steps precision predict drug sensitivity from translational point view. Genomic developments their implications discussed, along advancements that could broaden applications. Current achievements put perspective provide an overview state-of-art oncology as well identify future research directions.

Language: Английский

Citations

9
Pharmacological insights on novel oral selective estrogen receptor degraders in breast cancer DOI Creative Commons

Giorgio Guglielmi,

Marzia Del Re,

Leila Sadeghi Gol

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 969, P. 176424 - 176424

Published: Feb. 23, 2024

The therapeutic landscape of estrogen receptor (ER)-positive breast cancer includes endocrine treatments with aromatase inhibitors (AIs), selective modulators (SERMs), and degraders (SERDs). Fulvestrant is the first approved SERD proven efficacy good tolerability in clinical practice. However, secondary drug resistance, low affinity, parental administration stimulated search for new oral SERDs opening a era ER + cancer. Elacestrant an orally bioavailable that has been recently by FDA postmenopausal women ER+, human epidermal growth factor 2-negative (HER2-), 1 (ESR1)-mutated advanced or metastatic disease progression following at least one line therapy. Other molecules same class currently tested trials are amcenestrant, giredestrant, camizestrant, imlunestrant. current review article offers detailed pharmacological perspective this emerging class, which may help their possible future applications.

Language: Английский

Citations

8
Detection rate for ESR1 mutations is higher in circulating‐tumor‐cell‐derived genomic DNA than in paired plasma cell‐free DNA samples as revealed by ddPCR DOI Creative Commons
Stavroula Smilkou, Aliki Ntzifa,

Victoria Tserpeli

et al.

Molecular Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Plasma cell‐free DNA (cfDNA) analysis to track estrogen receptor 1 ( ESR1 ) mutations is highly beneficial for the identification of tumor molecular dynamics and improvement personalized treatments patients with metastatic breast cancer (MBC). Plasma‐cfDNA is, up now, most frequent liquid biopsy analyte used evaluate mutational status. Circulating cell (CTC) enumeration characterization provides important clinical information in MBC. In this study, we investigated whether CTCs circulating (ctDNA) provide similar or complementary mutations. We analyzed both plasma‐cfDNA n = 90) paired CTC‐derived genomic (gDNA; 42) from 90 MBC seven Eight out (8.9%) samples tested using ddPLEX Mutation Detection Assay (Bio‐Rad, Hercules, CA, USA), were found positive one mutation, whereas 11/42 (26.2%) gDNA at least mutation. Direct comparison revealed that mutation rate was higher (11/42, 26.2%) than (6/42, 14.3%) samples. Our results, sensitive assay, reveal a percentage gDNAs ctDNA should be further evaluated as an tool identifying guiding individualized therapy.

Language: Английский

Citations

1
Efficacy and Safety of CDK4/6 Inhibitors: A Focus on HR+/HER2− Early Breast Cancer DOI Creative Commons

Eva Valentina Klocker,

Daniel Egle,

Rupert Bartsch

et al.

Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the treatment of hormone-receptor positive (HR+), HER2 negative (HER2−) metastatic breast cancer, and are now also established agents in high-risk intermediate-risk HR+ early cancer. Several strategies regarding CDK4/6i combinations or continuation beyond progression been successfully evaluated setting, considered a standard care. Mechanism action resistance mechanisms against addition to endocrine represent an important research topic, for Clinically, efficient substances that usually well tolerated. However, side effects differing between reported, might lead discontinuation, including disease setting. In adjuvant palbociclib has not improved outcomes, whereas large randomized phase III trials demonstrated significant disease-free survival benefit ribociclib (NATALEE trial) abemaciclib (monarchE trial). Patient selection, duration, backbone therapy, other study details differ these pivotal trials. This review focuses on both scientific background as all available clinical data CDK4/6i, with particular emphasis their use

Language: Английский

Citations

1
Optimizing therapeutic approaches for HR+/HER2- advanced breast cancer: clinical perspectives on biomarkers and treatment strategies post-CDK4/6 inhibitor progression DOI Open Access

J.M. Cejalvo Andujar,

Francisco Ayala de la Peña, Mireia Margelí Vila

et al.

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

This review offers an expert perspective on biomarkers, CDK4/6 inhibitor efficacy, and therapeutic approaches for managing hormone receptor-positive (HR+), human epidermal growth factor receptor-negative (HER2-) advanced breast cancer (ABC), particularly after progression. Key trials have demonstrated that combining inhibitors with endocrine therapy (ET) significantly improves progression-free survival (PFS), median durations ranging from 14.8 to 26.7 months, overall (OS), reaching up 53.7 months. Actionable such as PIK3CA ESR1 mutations, emerged pivotal tools guide second-line treatment decisions, enabling the use of targeted therapies like alpelisib elacestrant emphasizing important role biomarkers in guiding selection therapy. overview aims provide clinicians a practical up-to-date framework inform decisions improve patient care context this challenging disease. Additionally, we emerging novel strategies address difficult clinical landscape.

Language: Английский

Citations

1