AI Article Synopsis
- The study examines the relationship between HER2 and ESR1 expression levels and treatment outcomes for HER2-positive breast cancer patients in the GeparQuattro trial.
- Only 73% of tumors were confirmed as cHER2-positive, with these showing significantly higher pCR rates compared to cHER2-negative tumors.
- HER2 mRNA levels were linked to treatment response in ESR1-positive tumors, indicating that the biology of HER2-positive breast cancers can vary based on ESR1 status.
Article Abstract
Introduction: Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies of HER2-positive breast carcinomas from patients treated within the neoadjuvant GeparQuattro trial.
Methods: HER2 levels were centrally analyzed by immunohistochemistry (IHC), silver in situ hybridization (SISH) and qRT-PCR in 217 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) core biopsies. All tumors had been HER2-positive by local pathology and had been treated with neoadjuvant trastuzumab/ chemotherapy in GeparQuattro.
Results: Only 73% of the tumors (158 of 217) were centrally HER2-positive (cHER2-positive) by IHC/SISH, with cHER2-positive tumors showing a significantly higher pCR rate (46.8% vs. 20.3%, P <0.0005). HER2 status by qRT-PCR showed a concordance of 88.5% with the central IHC/SISH status, with a low pCR rate in those tumors that were HER2-negative by mRNA analysis (21.1% vs. 49.6%, P <0.0005). The level of HER2 mRNA expression was linked to response rate in ESR1-positive tumors, but not in ESR1-negative tumors. HER2 mRNA expression was significantly associated with pCR in the HER2-positive/ESR1-positive tumors (P = 0.004), but not in HER2-positive/ESR1-negative tumors.
Conclusions: Only patients with cHER2-positive tumors - irrespective of the method used - have an increased pCR rate with trastuzumab plus chemotherapy. In patients with cHER2-negative tumors the pCR rate is comparable to the pCR rate in the non-trastuzumab treated HER-negative population. Response to trastuzumab is correlated to HER2 mRNA levels only in ESR1-positive tumors. This study adds further evidence to the different biology of both subsets within the HER2-positive group.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672694 | PMC |
| http://dx.doi.org/10.1186/bcr3384 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Impact of the Coexpression of and Genes on Prognosticators and Clinical Outcomes of Breast Cancer: An Analysis for the METABRIC Dataset.
Breast J
January 2025
Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, Medical University of South Carolina, 70 President St., Charleston, SC 29425, USA.
Purpose: Breast cancer is a heterogeneous disease. Exploring new prognostic and therapeutic targets in patients with breast cancer is essential. This study investigated the expression of MET, ESR1, and ESR2 genes and their association with clinicopathologic characteristics and clinical outcomes in patients with breast cancer.
View Article and Find Full Text PDFAbemaciclib Plus Fulvestrant in Advanced Breast Cancer Following Progression on CDK4/6 Inhibition: Results from the Phase III postMONARCH Trial.
J Clin Oncol
December 2024
Massachusetts General Hospital, Harvard University, Boston, MA, USA.
Purpose: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are the standard first-line treatment for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC); however, disease progression occurs in almost all patients and additional treatment options are needed. Herein we report outcomes of the postMONARCH trial investigating a switch in ET with/without CDK4/6 inhibition with abemaciclib after disease progression on CDK4/6i.
Methods: This double-blind, randomized Phase III study enrolled patients with disease progression on prior CDK4/6i plus aromatase inhibitor as initial therapy for advanced disease or recurrence on/after adjuvant CDK4/6i+ET.
Molecular Profiling of Endocrine Resistance in HR+/HER2-Metastatic Breast Cancer: Insights from Extracellular Vesicles-Derived DNA and ctDNA in Liquid Biopsies.
Int J Mol Sci
December 2024
"Clinical and Translational Research in Oncology" Group, Molecular Oncology Laboratory, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), 28040 Madrid, Spain.
Standard treatments in hormone receptor-positive (HR+)/HER2-metastatic breast cancer (mBC) typically involve endocrine therapy (ET) combined with CDK4/6 inhibitors, yet resistance to ET remains a persistent challenge in advanced cases. A deeper knowledge of the use of liquid biopsy is crucial for the implementation of precision medicine in mBC with real-time treatment guidance. Our study assesses the prognostic value of and mutations in DNA derived from extracellular vesicles (EV-DNA) in longitudinal plasma from 59 HR+/HER2-mBC patients previously exposed to aromatase inhibitors, with a comparative analysis against circulating tumor DNA (ctDNA).
View Article and Find Full Text PDFNeoadjuvant HER2 inhibition induces ESR1 DNA methylation alterations resulting in clinically relevant ER expression changes in breast cancers.
Cancer Commun (Lond)
December 2024
Department of Surgery, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
Imlunestrant with or without Abemaciclib in Advanced Breast Cancer.
N Engl J Med
December 2024
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (K.L.J.); University Hospitals Leuven, Leuven, Belgium (P.N.); Hospital María Curie, Buenos Aires (M.L.C.); Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (S.-B.K.); National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan (E.T.); Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels (P.A.); Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona (C.S.); Baylor University Medical Center, Texas Oncology, U.S. Oncology, Dallas (J.O.); the Breast Center, Department of Obstetrics and Gynecology and Comprehensive Cancer Center Munich, Ludwig Maximilians University Munich University Hospital, Munich, Germany (N.H.); the University of North Carolina at Chapel Hill, Chapel Hill (L.A.C.); the University of Milan, Milan (G.C.); the European Institute of Oncology, IRCCS, Milan (G.C.); Hospital Arnau de Vilanova, Valencia, Spain (A.L.-C.); Garvan Institute of Medical Research and University of New South Wales, Sydney (E.L.); Hospital de Oncología, Centro Médico Nacional Siglo XXI, Mexico City (M.L.G.T.); Yonsei University College of Medicine, Seoul, South Korea (J.S.); the Mastology Department, Women's Health Hospital, São Paulo (A.M.); Harbin Medical University Cancer Hospital, Harbin, China (Q.Z.); National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei (C.-S.H.); the Division of Breast Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan (C.-C.H.); Filios Alta Medicina, Monterrey, Mexico (J.L.M.R.); the Medical Oncology Department, Hospital Universitario Virgen del Rocío, Seville, Spain (M.R.B.); the Department of Breast Surgery, Chiba Cancer Center Hospital, Chiba, Japan (R.N.); Eli Lilly, Indianapolis (K.R.P., C.C.L., E.B., S.C., X.A.W., L.M.S.); and Institut Curie and University of Versailles Saint-Quentin-en-Yvelines-Paris-Saclay University, Paris (F.-C.B.).
Background: Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα ().
Methods: In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!