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.
Qianchen Zhang, Jincong Q Freeman, Fangyuan Zhao, Nan Chen, Rita Nanda, Dezheng Huo, Frederick M Howard
{"title":"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.","authors":"Qianchen Zhang, Jincong Q Freeman, Fangyuan Zhao, Nan Chen, Rita Nanda, Dezheng Huo, Frederick M Howard","doi":"10.1200/oa.24.00016","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Human 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.</p><p><strong>Methods: </strong>This 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.</p><p><strong>Results: </strong>We 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], <i>P</i> < .001) and group 2 (aOR, 2.38 [95% CI, 1.42 to 3.96], <i>P</i> < .001) treated with HER2-targeted therapy had higher pCR than HER2- controls. Benefit was also seen in group 3 (aOR, 1.63 [95% CI, 1.24 to 2.13], <i>P</i> < .001) and cases with discordant ISH+/IHC- (aOR, 1.61 [95% CI, 1.13 to 2.30], <i>P</i> = .008)-but this was only significant in group 3 cases with copy number ≥8 and discordant ISH+/IHC- cases with HER2/CEP17 ratio ≥3. Group 4 ISH cases and cases with ISH-/IHC+ did not benefit.</p><p><strong>Conclusion: </strong>Patients 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.</p>","PeriodicalId":520350,"journal":{"name":"JCO oncology advances","volume":"1 ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422704/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCO oncology advances","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1200/oa.24.00016","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/12 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: Human 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.
Methods: This 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.
Results: We 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], P < .001) and group 2 (aOR, 2.38 [95% CI, 1.42 to 3.96], P < .001) treated with HER2-targeted therapy had higher pCR than HER2- controls. Benefit was also seen in group 3 (aOR, 1.63 [95% CI, 1.24 to 2.13], P < .001) and cases with discordant ISH+/IHC- (aOR, 1.61 [95% CI, 1.13 to 2.30], P = .008)-but this was only significant in group 3 cases with copy number ≥8 and discordant ISH+/IHC- cases with HER2/CEP17 ratio ≥3. Group 4 ISH cases and cases with ISH-/IHC+ did not benefit.
Conclusion: Patients 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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
