50P HER2/HER3 heterodimerization can define ER+/HER2-low breast cancer as a distinct biological entity

HER2-low breast cancer is emerging as a specific subtype of tumor against which trastuzumab-containing antibody-drug conjugates, specifically trastuzumab-deruxtecan, are effective. However, attempts to define tumors unique biological entity have thus far concluded that low HER2 expression does not categorize these having distinct molecular features beyond immunohistochemical (IHC) cytoplasmic membrane HER2. Our aim in this study characterize separate entities and establish whether there other mechanisms at play can be exploited therapeutical approaches trastuzumab-deruxtecan. We selected cohort patients within the large population-based SCAN-B prospective study. included all diagnosed Region Skåne between 2010 2014 with follow-up ≥ 5 years. only histology invasive ductal carcinoma (IDC) ensure homogeneity. All cases had complete RNA-sequencing profiling. Tumors were ER positive, defined IHC staining ≥10% cells, negative (0-1+ by or 2+ no amplification ISH). The disease scores 1+ gene amplification, per international guidelines. identified 1299 cohort. As earlier described cohorts, do show worse prognosis regarding event-free interval overall survival. strength correlates ERBB2 mRNA data linearly. Intriguingly, we found positive correlation ERBB3 but potential heterodimerization partners such EGFR, ERBB4, AXL. suggests heterodimers form activate internal signaling disease. now looking patterns elucidate if HER2/HER3 association corresponds tumors.