Clinical characterization, prognostic, and predictive values of HER2-low in patients with early breast cancer in the PALLAS trial (ABCSG-42/AFT-05/BIG-14-13/PrE0109).

Autor: Nader-Marta G; Institut Jules Bordet, Academic Trials Promoting Team (ATPT), Université Libre de Bruxelles (U.L.B), Hôpital Universitaire de Bruxelles (HUB), Brussels, Belgium. guilherme_nadermarta@dfci.harvard.edu.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. guilherme_nadermarta@dfci.harvard.edu.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA. guilherme_nadermarta@dfci.harvard.edu.; Harvard Medical School, Boston, MA, USA. guilherme_nadermarta@dfci.harvard.edu., Singer C; Department of Obstetrics and Gynaecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Hlauschek D; Austrian Breast and Colorectal Cancer Study Group (ABCSG), Vienna, Austria., DeMichele A; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA., Tarantino P; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy., de Azambuja E; Institut Jules Bordet, Academic Trials Promoting Team (ATPT), Université Libre de Bruxelles (U.L.B), Hôpital Universitaire de Bruxelles (HUB), Brussels, Belgium., Pfeiler G; Department of Obstetrics and Gynaecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Martin M; Hospital General Universitario Gregorio Marañón, Madrid, Spain., Balko JM; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA., Nowecki Z; The Maria Sklodowska Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland., Balic M; Division of Oncology, Department of Internal Medicine, Medical University Graz, Graz, Austria.; University of Pittsburgh Hillman Cancer Center, Magee-Women's Hospital, Pittsburgh, PA, USA., Brufsky AM; University of Pittsburgh Hillman Cancer Center, Magee-Women's Hospital, Pittsburgh, PA, USA., Chan A; Breast Cancer Research Centre-WA & Curtin University, Perth, Australia., Morris PG; Cancer Trials Ireland, Dublin, Ireland.; Beaumont RCSI Cancer Centre, Dublin, Ireland., Haddad T; Mayo Clinic Comprehensive Cancer Center, Rochester, MN, USA., Loibl S; German Breast Group, Prof. (Apl), Goethe University Frankfurt, Frankfurt am Main, Germany.; Clinical Consultant Centre for Haematology and Oncology/Bethanien, Frankfurt, Germany., Liu Y; Translational Oncology Global Product Development Pfizer Inc, San Diego, CA, USA., Soelkner L; Austrian Breast and Colorectal Cancer Study Group (ABCSG), Vienna, Austria., Fesl C; Austrian Breast and Colorectal Cancer Study Group (ABCSG), Vienna, Austria., Mayer EL; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Gnant M; Austrian Breast and Colorectal Cancer Study Group (ABCSG), Vienna, Austria.; Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Jazyk: angličtina
Zdroj: Breast cancer research : BCR [Breast Cancer Res] 2024 Oct 07; Vol. 26 (1), pp. 140. Date of Electronic Publication: 2024 Oct 07.
DOI: 10.1186/s13058-024-01899-2
Abstrakt: Background: Bidirectional crosstalk between HER2 and estrogen receptor (ER) pathways may influence outcomes and the efficacy of endocrine therapy (ET). Low HER2 expression levels (HER2-low) have emerged as a predictive biomarker in patients with breast cancer (BC).
Methods: PALLAS is an open, international, phase 3 study evaluating the addition of palbociclib for 2 years to adjuvant ET in patients with stage II-III ER-positive/HER2-negative BC. To assess the impact of HER2 expression on patient outcomes in the phase III PALLAS trial, we analyzed (1) the association between rate of HER2-low with demographic and clinicopathological parameters, (2) the prognostic value of HER2-low status on invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS) and (3) HER2 expression's value as a predictive biomarker of response to palbociclib. HER2-low was defined as HER2 immunohistochemistry (IHC) 1 + or IHC 2 + with negative in situ hybridization (ISH). All pathologic evaluation was performed locally. Prognostic and predictive power of HER2 were assessed with Cox models.
Results: From the original PALLAS intention-to-treat population (N = 5753), 5304 patients (92.2%) were included in this analysis. Among these, 2254 patients (42.5%) were classified as having HER2 IHC 0 (HER2-0), and 3050 (57.5%) as having HER2-low disease (1838 with IHC 1 + and 1212 with IHC 2 +). Median follow-up was 59.8 months. HER2-low prevalence varied significantly across 21 participating countries (range 16.7% to 75.6%; p < 0.001) and was more frequent in patients enrolled in North America (63.1%) than in Europe (53.4%) or other regions (53.4%) (p < 0.001). HER2 status was not significantly associated with iDFS in a multivariable Cox model (hazard ratio 0.93, 95% confidence interval 0.81 - 1.06). No significant interaction was observed between treatment arm and HER2 status for iDFS (p = 0.43). Similar results were obtained for DRFS and OS.
Conclusions: In this large, prospective, global patient cohort, no differences were observed in clinical parameters, prognosis, or differential benefit from palbociclib between HER2-0 and HER2-low tumors. Significant geographic variability was observed in the prevalence of HER2-low status, suggesting a high degree of variation in pathologic assessment of HER2 expression without impact on outcomes.
(© 2024. The Author(s).)
Databáze: MEDLINE
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