Elisa Agostinetto1,2,3, Mattia Rediti4, Danai Fimereli4, Véronique Debien1, Martine Piccart5, Philippe Aftimos6, Christos Sotiriou4, Evandro de Azambuja1. 1. Academic Trials Promoting Team, Institut Jules Bordet, l'Université Libre de Bruxelles (U.L.B), 1000 Brussels, Belgium. 2. Humanitas Clinical and Research Center-IRCCS, Humanitas Cancer Center, Via Manzoni 56, 20089 Milan, Italy. 3. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy. 4. Breast Cancer Translational Research Laboratory J.-C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, 1000 Brussels, Belgium. 5. Medical Oncology Department, Institut Jules Bordet, 1000 Brussels, Belgium. 6. Clinical Trials Conduct Unit, Institut Jules Bordet-Université Libre de Bruxelles, 1000 Brussels, Belgium.
Abstract
BACKGROUND: We aimed to determine the distribution of intrinsic subtypes within HER2-low breast cancer (BC), and to describe the prognostic impact of HER2-low status on survival outcomes. METHODS: This is a retrospective, observational study of primary BC extracted from The Cancer Genome Atlas dataset. We described the distribution of PAM50 intrinsic subtypes within HER2-low BC subtype according to hormonal receptor status (positive (HR+) and negative (HR-)). Secondly, we assessed the impact of HER2-low on survival outcomes (progression-free interval (PFI), disease-free interval (DFI), and overall survival (OS)). RESULTS: We analyzed 804 primary BCs, including 410 (51%) HER2-low BCs (336 HR+ and 74 HR-). The proportion of HER2-enriched tumors was higher in the HER2-low/HR- group compared to HER2-low/HR+ (13.7% versus 1.2%, respectively). HER2-enriched tumors were more frequent in HER2-low/HR- and HER2-low/HR+ subtypes, compared to HER2-negative/HR- and HER2-negative/HR+ subtypes, respectively (13.7% versus 1.6% and 1.2% versus 0.5%, respectively). We observed no significant differences in PFI, DFI, and OS between HER2-low subtypes and each non-HER2-low subtype paired by HR status. CONCLUSIONS: Our characterization of PAM50 intrinsic subtypes within HER2-low breast cancer may explain the different clinical behaviors and responses to treatment, and ultimately support further investigation of new treatment strategies in the HER2-low category. Moreover, it highlights the importance of considering HR status in the HER2-low category.
BACKGROUND: We aimed to determine the distribution of intrinsic subtypes within HER2-low breast cancer (BC), and to describe the prognostic impact of HER2-low status on survival outcomes. METHODS: This is a retrospective, observational study of primary BC extracted from The Cancer Genome Atlas dataset. We described the distribution of PAM50 intrinsic subtypes within HER2-low BC subtype according to hormonal receptor status (positive (HR+) and negative (HR-)). Secondly, we assessed the impact of HER2-low on survival outcomes (progression-free interval (PFI), disease-free interval (DFI), and overall survival (OS)). RESULTS: We analyzed 804 primary BCs, including 410 (51%) HER2-low BCs (336 HR+ and 74 HR-). The proportion of HER2-enriched tumors was higher in the HER2-low/HR- group compared to HER2-low/HR+ (13.7% versus 1.2%, respectively). HER2-enriched tumors were more frequent in HER2-low/HR- and HER2-low/HR+ subtypes, compared to HER2-negative/HR- and HER2-negative/HR+ subtypes, respectively (13.7% versus 1.6% and 1.2% versus 0.5%, respectively). We observed no significant differences in PFI, DFI, and OS between HER2-low subtypes and each non-HER2-low subtype paired by HR status. CONCLUSIONS: Our characterization of PAM50 intrinsic subtypes within HER2-low breast cancer may explain the different clinical behaviors and responses to treatment, and ultimately support further investigation of new treatment strategies in the HER2-low category. Moreover, it highlights the importance of considering HR status in the HER2-low category.
Entities:
Keywords:
HER2-low; PAM50; TCGA; breast cancer; prognosis
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