ArticleJCO oncology advances2024
Clinical Outcomes and Efficacy of Human Epidermal Growth Factor Receptor 2-Targeted Therapy in Breast Cancer With Uncommon In Situ Hybridization Patterns or Discordant Immunohistochemistry.
Article in JCO oncology advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeHuman epidermal growth factor receptor 2 (HER2)-targeted therapy improves outcomes in HER2+ breast cancer, but efficacy in cases with discordant immunohistochemistry (IHC) and in situ hybridization (ISH) results or with ASCO/College of American Pathologists (CAP) group 2-4 ISH results remains uncertain.
methodsThis retrospective study included patients from the National Cancer Database diagnosed from 2013 to 2021. Cases were classified as classically HER2+ (HER2/centromeric region of chromosome 17 [CEP17] ratio ≥2 with HER2 copy number ≥4, IHC 2-3+), HER2- (ratio <2, copy number <4, IHC 0-2+), discordant ISH/IHC, or HER2+ with ISH group 2 (ratio ≥2, copy number <4), group 3 (ratio <2, copy number ≥6), or group 4 (ratio <2, copy number ≥4 and <6) per ASCO/CAP guidelines. Adjusted odds ratio (aOR) for pathologic complete response (pCR) for these subgroups receiving HER2-targeted therapy was calculated compared with HER2- controls.
resultsWe identified N = 144,013 patients with IHC and dual-probe ISH. Of HER2 IHC 3+ cases (n = 8,579), 8.2%, 2.8%, 4.2%, and 8.8% had ISH categorized as groups 2, 3, 4, and 5 (discordant negative), respectively. Classically, HER2+ (aOR, 2.9 [95% CI, 2.65 to 3.18],
conclusionPatients with ASCO/CAP group 4, discordant ISH-/IHC+ results, and weakly amplified group 3 and discordant ISH+/IHC- have low benefit from HER2 therapy, and alternative approaches for such patients are needed.
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