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Reclassifying 367 chemotherapy-naive triple-negative cancers put 38% in HER2-null, 38% in HER2-ultralow and 24% in HER2-low; the categories differed a little in size, grade and BRCA1 methylation but not in relapse over ten years.
367 patients with non-metastatic TNBC who never received chemotherapy were reclassified: HER2 0 tumours as HER2-null (no staining) or HER2-ultralow (10% or fewer cells with faint incomplete membrane staining); 1+ or non-amplified 2+ as HER2-low. 38.4% were null, 37.6% ultralow and 24.0% low. Ultralow tumours were more often associated with tertiary lymphoid structures (P 0.0259) and BRCA1 promoter methylation (P 0.0439) than low tumours, and were smaller and of lower stage and grade than null tumours. Age, nodal status, histology, molecular apocrine or basal-like phenotype, PIK3CA and PTEN status, CD3, CD20 and CD163 infiltrates and PD-L1 did not differ. Relapse-free survival at a median 10.3 years was unaffected by HER2 category.
Three-quarters of chemotherapy-naive TNBC would be low or ultralow by the DESTINY-Breast06 definitions, but ultralow is unlabelled in TNBC and carries no prognostic weight.
Shares HER2 IHC 0 (HER2-negative, including ultralow), HER2-low (IHC 1+ or IHC 2+/ISH-negative), HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH), HER2-low and HER2-ultralow.
Shares HER2-ultralow (IHC 0 with membrane staining), HER2-low (IHC 1+ or IHC 2+/ISH-negative), HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH), HER2-low and HER2-ultralow.
Shares HER2-low (IHC 1+ or IHC 2+/ISH-negative), HER2-low and HER2-ultralow, Early triple-negative breast cancer, HER2.
Shares HER2-ultralow (IHC 0 with membrane staining), HER2-low and HER2-ultralow, Immunohistochemistry (IHC), Trastuzumab deruxtecan.
Shares HER2-low (IHC 1+ or IHC 2+/ISH-negative), HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH), HER2-low and HER2-ultralow, Immunohistochemistry (IHC).
Shares HER2-low and HER2-ultralow, Early triple-negative breast cancer, Triple-negative breast cancer (TNBC).
Shares HER2 IHC 0 (HER2-negative, including ultralow), HER2-ultralow (IHC 0 with membrane staining), HER2-low (IHC 1+ or IHC 2+/ISH-negative), HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH).
Shares HER2-low and HER2-ultralow, Trastuzumab deruxtecan, HER2, Triple-negative breast cancer (TNBC).