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)
Year: 2024
Type: article
Abstract: 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.
Source: Breast Cancer Research
Authors: Guilherme Nader-Marta, Christian Singer, Dominik Hlauschek, Angela DeMichele, Paolo Tarantino, Evandro de Azambuja, Georg Pfeiler, Miguel Martin, Justin M. Balko, Zbigniew Nowecki, Marija Balic, Adam M. Brufsky, Arlene Chan, Patrick G. Morris, Tufia Haddad, Sibylle Loibl, Yuan Liu, Lidija Soelkner, Christian Fesl, Erica L. Mayer, Michael Gnant, on behalf of the PALLAS groups and investigators
Institutions: Université Libre de Bruxelles, Harvard University, Institut Jules Bordet, Dana-Farber Cancer Institute, Dana-Farber/Harvard Cancer Center, Dana-Farber Brigham Cancer Center, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austrian Breast & Colorectal Cancer Study Group, Abramson Cancer Center, University of Pennsylvania, University of Milan, Hospital General Universitario Gregorio Marañón, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, The Maria Sklodowska-Curie National Research Institute of Oncology, University of Pittsburgh, Medical University of Graz, Magee-Womens Hospital, UPMC Hillman Cancer Center, Curtin University, Royal College of Surgeons in Ireland, Beaumont Hospital, Cancer Trials Ireland, Mayo Clinic, Mayo Clinic Comprehensive Cancer Center (Minnesota), Goethe University Frankfurt, German Breast Group, Pfizer (United States)
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,990
OpenAlex ID: W4403185271