Abstract
Simple SummaryThe dichotomous classification of HER2 status is experiencing a paradigm change, leading to the identification of the so-called “HER2-low” category. The aim of our retrospective, observational study was to characterize intrinsic PAM50 subtypes within HER2-low primary breast tumors extracted from The Cancer Genome Atlas (TCGA) dataset and to describe the prognostic impact of HER2-low on survival outcomes. We evaluated 804 breast cancers and we identified 410 HER2-low tumors (336 with positive hormonal receptor status (HR+) and 74 with negative HR status (HR−)). 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 prognosis between HER2-low subtypes and each non-HER2-low subtype when paired by HR status. Our characterization of PAM50 intrinsic subtypes within HER2-low breast cancer ultimately supports further investigation of new treatment strategies in the HER2-low category, with new promising drugs being tested in the context.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.
Highlights
The characterization of the Human Epidermal Growth Factor Receptor-2 (HER2) in breast cancer (BC) has dramatically evolved over the last three decades, from a biomarker of poor prognosis to one of clinical benefit for trastuzumab and other anti-HER2 agents, when overexpressed/amplified in tumor cells [1,2,3,4,5]
We identified 410 (51%) HER2-low BC, of which 336 hormone receptors (HRs)+ (41.8%) and 74 HR− (9.2%)
We presented the distribution of BC subtypes (HER2−/HR+, HER2+/HR+, HER2+/HR−, HER2-low/HR+, HER2-low/HR−, HER2−/HR−) according to PAM50 intrinsic subtypes
Summary
The characterization of the Human Epidermal Growth Factor Receptor-2 (HER2) in breast cancer (BC) has dramatically evolved over the last three decades, from a biomarker of poor prognosis to one of clinical benefit for trastuzumab and other anti-HER2 agents, when overexpressed/amplified in tumor cells [1,2,3,4,5]. The HER2-low BC subtype represents a new recently proposed nomenclature for those tumors with an immunohistochemistry (IHC) assay score of 1+ or 2+ but with negative in situ hybridization (ISH) assay [7,10] In clinical practice, these tumors are classified as triple-negative BC (TNBC) or, if hormone receptors (HRs) are expressed, as luminal BC, being considered to not benefit from anti-HER2 treatments. Conclusions: Our characterization of PAM50 intrinsic subtypes within HER2-low breast cancer may explain the different clinical behaviors and responses to treatment, and support further investigation of new treatment strategies in the HER2-low category. It highlights the importance of considering HR status in the HER2-low category
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
