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HER2 Biology and Testing in GI, GU, and GYN

CME

HER2: Biology and Testing in Gastrointestinal, Genitourinary, and Gynecologic Malignancies

Physicians: Maximum of 0.25 AMA PRA Category 1 Credit

Released: August 04, 2025

Expiration: February 03, 2026

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References

  1. Raghav K, et al; Molecular Pathways and Mechanisms of HER2 in Cancer Therapy. Clin Cancer Res. 2023; 29: 2351.
  2. Cheng X. A Comprehensive review of HER2 in cancer biology and therapeutics. Genes. 2024;15:903-903.
  3. Bremer A, Wik E, Akslen LA. HER2 revisited: reflections on the future of cancer biomarker research. In: Bremer A, Strand R, editors. Precision Oncology and Cancer Biomarkers. Human Perspectives in Health Sciences and Technology, vol 5. Springer. 2022.‌
  4. Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. New Engl J Med. 2011;365:1273-1283.
  5. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687-697.
  6. Michelon I, Dacoregio MI, Vilbert M, et al. Antibody-drug conjugates (ADC) in patients with advanced/metastatic HER2-low expressing breast cancer: A systematic review and meta-analysis. Presented at: American Society of Clinical Oncology Annual Meeting. May 31-June 4, 2024; Abstract e13174.
  7. Ecaterina E., et al. Targeting ERBB2 (HER2) amplification identified by next-generation sequencing in patients with advanced or metastatic solid tumors beyond conventional indications. JCO Precis Oncol. 2019;3:1:12.
  8. Sundar R, Nakayama I, Markar SR, et al. Gastric cancer. Lancet. 2025;405:2087-2102.
  9. Shimozaki K, Fukouka S, Ooki A, et al. HER2-low gastric cancer: is the subgroup targetable? ESMO Open. 2024;9:103679.
  10. Rüschoff J, Hanna W, Bilous M, et al. HER2 testing in gastric cancer: a practical approach. Modern Pathology. 2012;25:637-650.
  11. Ma C, Wang X, Guo J, et al. Challenges and future of HER2-positive gastric cancer therapy. Frontiers in Oncology. 2023;13:1080990.
  12. Smolenschi C, Blanc J, Lancry A, et al. Real-world efficacy of zanidatamab in patients with HER2 positive advanced biliary tract cancers. Eur J Cancer, 2025;222:115432.
  13. Buza N. HER2 Testing in Endometrial Serous Carcinoma: Time for Standardized Pathology Practice to Meet the Clinical Demand. Arch Pathol Lab Med. 2021;145:687-691.
  14. Balestra A, Larsimont D, Noël J. HER2 Amplification in p53-mutated endometrial carcinomas. Cancers (Basel). 2023;15:1435-1435.
  15. Lee D, Kim Y-N, Park J, et al. HER2 expression in ovarian cancer: Its relationship with HRD status, and other biomarkers. Presented at: European Society for Medical Oncology Gynaecological Cancers Congress; March 7-10, 2024. Abstract 765P.
  16. Itkin B, Garcia A, Straminsky S, et al. Prevalence of HER2 overexpression and amplification in cervical cancer: A systematic review and meta-analysis. PLoS One. 2021;16:e0257976.
  17. National Comprehensive Cancer Network. NCCN guidelines: ovarian cancer/fallopian tube cancer/primary peritoneal cancer. Version 3.2025. nccn.org. Accessed July 31, 2025.
  18. Scherrer E, Kang A, Bloudek LM, Koshkin VS. HER2 expression in urothelial carcinoma, a systematic literature review. Front Oncol. 2022;12:1011885.
  19. Ortiz-Calderon IA, Arias-Ruiz LF, Dorantes-Heredia R, et al. Prevalence and clinical outcomes of human epidermal growth factor receptor 2 expression in patients with advanced urothelial carcinoma. World J Oncol. 2025;16:51-58.
  20. Shaaban AM, Kaur T, Provenzano E. HER2-low breast cancer—Current knowledge and future directions. Medicina. 2025;61:644.
  21. Wolff AC, Somerfield MR, Dowsett M, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology–College of American Pathologists guideline update. Arch Pathol Lab Med. 2023;147:993-1000.
  22. Ivanova M, Porta FM, D’Ercole M, et al. Standardized pathology report for HER2 testing in compliance with 2023 ASCO/CAP updates and 2023 ESMO consensus statements on HER2-low breast cancer. Virchows Archiv. 2023;484:3-14.
  23. Shami, R. et al. Analytical and clinical validation of PATHWAY HER2 (4B5) assay for assessment of HER2-low/HER2-ultralow status and eligibility for trastuzumab deruxtecan in DESTINY-Breast06. ESMO Open. 2025;10,6:105310.
  24. Bartley AN, Washington MK, Ventura CB, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology. Arch Pathol Lab Med. 2016;140:1345-1363.
  25. Bryant D, et al. A real-world experience in pan-tumor testing for HER2 IHC in more than 65 000 solid tumors. JAMA Oncol. 2025;[Epub ahead of print].
  26. National Comprehensive Cancer Network. NCCN guidelines: Gastric Cancer. Version 2.2025. nccn.org. Accessed July 31, 2025.
  27. National Comprehensive Cancer Network. NCCN guidelines: Colon Cancer. Version 4.2025. nccn.org. Accessed July 31, 2025.
  28. National Comprehensive Cancer Network. NCCN guidelines: Biliary Tract Cancers. Version 1.2025. nccn.org. Accessed July 31, 2025.
  29. National Comprehensive Cancer Network. NCCN guidelines: Uterine Neoplasms. Version 3.2025. nccn.org. Accessed July 31, 2025.
  30. Lee D, Kim et al Park J. 765P HER2 expression in ovarian cancer: Its relationship with HRD status, and other biomarkers. Ann Oncol. 2024; 35:579.
  31. National Comprehensive Cancer Network. NCCN guidelines: Bladder Cancer. Version 1.2025. nccn.org. Accessed July 31, 2025.
  32. Robbins CJ, Bates KM, Rimm DL. HER2 testing: Evolution and update for a companion diagnostic assay. Nat Rev Clin Oncol. 2025;22:408.
  33. Aro K, Loukovaara M, Butzow R, et al. HER2 amplification and HER2 low expression in endometrial carcinoma: prevalence across molecular, histological and clinicopathological risk groups. BJC Rep. 2025;3:8.
  34. Nicolò E, Boscolo Bielo L, Curigliano G, et al. The HER2-low revolution in breast oncology: steps forward and emerging challenges. Ther Adv Med Oncol. 2023;15:17588359231152842.
  35. He WZ, Yang YZ, Yin CX, et al. Evolution of HER2-low expression from primary to paired metastatic gastric cancer lesions. NPJ Precis. Onc. 2025;9:108.
  36. Zhang F and Sheng Li. Antibody-drug conjugates as game changers in bladder cancer: current progress and future directions. Front Immunol. 2025;16:1591191.
  37. Goodson D and Friedlander TW. The future of antibody–drug conjugates in urothelial cancer: New indications and novel targets. Adv Oncol. 2023;3:137-159.