Molecular Testing in EC

CE / CME

Molecular Testing for Key Biomarkers in Advanced Endometrial Cancer

ABIM MOC: maximum of 1.00 Medical Knowledge MOC point

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit

Released: November 02, 2023

Expiration: November 01, 2024

Activity

Progress
1 2
Course Completed

References

  1. Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17-48. 
  2. American Cancer Society. Endometrial cancer. cancer.org/cancer/types/endometrial-cancer.html. Accessed October 30, 2023.
  3. Kasius JC, Pijnenborg JMA, Lindemann K, et al. Risk stratification of endometrial cancer patients: FIGO stage, biomarkers and molecular classification. Cancers. 2021;13:5848.
  4. Walsh CS, Hacker KE, Secord AA, et al. Molecular testing for endometrial cancer: an SGO clinical practice statement. Gynecol Oncol. 2023;168:48-55. 
  5. Pembrolizumab [prescribing information]. North Wales, PA: Merck, Sharp and Dohme Corporation, a subsidiary of Merck & Co., Inc.; 2023.
  6. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: uterine neoplasms. v.1.2024. nccn.org. Accessed October 30, 2023.
  7. Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. 2023;388:2145-2158.
  8. Eskander RN, Sill MW, Beffa L, et al. Pembrolizumab plus chemotherapy in advanced endometrial cancer. N Engl J Med. 2023;388:2159-2170.
  9. Slomovitz BM, Pérez-Fidalgo JA, Hamilton EP, et al. Long-term follow up of selinexor maintenance in patients with TP53wt advanced or recurrent endometrial cancer: a pre-specified subgroup analysis from the phase 3 ENGOT-EN5/GOG-3055/SIENDO study. Presented at: American Society of Clinical Oncology Plenary Series; July 25, 2023. Abstract 427956.
  10. Vergote I, Pérez Fidalgo JA, Hamilton E, et al. SIENDO/ENGOT-EN5/GOG-3055: a randomized phase 3 trial of maintenance selinexor versus placebo after combination platinum-based chemotherapy in advanced or recurrent endometrial cancer. Presented at: 2022 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 18-21, 2022. Abstract 249.
  11. Meric-Bernstam F, Makker V, Oaknin A, et al. Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid tumors: DESTINY-PanTumor02 (DP-02) interim results. Presented at: 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023. Abstract LBA300.
  12. Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497:67-73.
  13. Li Y, Feng J, Zhao C, et al. A new strategy in molecular typing: the accuracy of an NGS panel for the molecular classification of endometrial cancers. Ann Transl Med. 2022;10:870.
  14. MacKay HJ, Levine DA, Bae-Jump VL, et al. Moving forward with actionable therapeutic targets and opportunities in endometrial cancer: NCI clinical trials planning meeting report on identifying key genes and molecular pathways for targeted endometrial cancer trials. Oncotarget. 2017;8:84579-84594.
  15. Javadian P, Washington C, Mukasa S, et al. Histopathologic, genetic and molecular characterization of endometrial cancer racial disparity. Cancers (Basel). 2021;13:1900.
  16. León-Castillo A, de Boer SM, Powell ME, et al. Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy. J Clin Oncol. 2020;38:3388-3397.
  17. Mitamura T, Dong P, Ihira K, et al. Molecular-targeted therapies and precision medicine for endometrial cancer. Jpn J Clin Oncol. 2019;49:108-120. 
  18. McAlpine J, Leon-Castillo A, Bosse T. The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses. J Pathol. 2018;244:538-549. 
  19. Pasanen A, Ahvenainen T, Pellinen T, et al. PD-L1 expression in endometrial carcinoma cells and intratumoral immune cells: differences across histologic and TCGA-based molecular subgroups. Am J Surg Pathol. 2020;44:174-181. 
  20. Stelloo E, Nout RA, Osse EM, et al. Improved risk assessment by integrating molecular and clinicopathological factors in early-stage endometrial cancer-combined analysis of the PORTEC cohorts. Clin Cancer Res. 2016;22:4215-4224.
  21. Salem ME, Bodor JN, Puccini A, et al. Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors. Int J Cancer. 2020;147:2948-2956.
  22. Antill Y, Buchanan DD, Scott CL. Mismatch repair and clinical response to immune checkpoint inhibitors in endometrial cancer. Cancer. 2022;128:1157-1161.
  23. Post CCB, Stelloo E, Smit VTHBM, et al. Prevalence and prognosis of Lynch syndrome and sporadic mismatch repair deficiency in endometrial cancer. J Natl Cancer Inst. 2021;113:1212-1220. 
  24. Crosbie EJ, Ryan NAJ, Arends MJ, et al. The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome. Genet Med. 2019;21:2390-2400.
  25. Allgäuer M, Budczies J, Christopoulos P, et al. Implementing tumor mutational burden (TMB) analysis in routine diagnostics-a primer for molecular pathologists and clinicians. Transl Lung Cancer Res. 2018;7:703-715. 
  26. Jardim DL, Goodman A, de Melo Gagliato D, et al. The challenges of tumor mutational burden as an immunotherapy biomarker. Cancer Cell. 2021;39:154-173. 
  27. Buza. HER2 testing in endometrial serous carcinoma: time for standardized pathology practice to meet the clinical demand. Arch Pathol Lab Med. 2020;145:687-691. 
  28. Fader AN, Roque DM, Siegel E, et al. Randomized phase II trial of carboplatin-paclitaxel compared with carboplatin-paclitaxel-trastuzumab in advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress Her2/Neu (NCT01367002): updated overall survival analysis. Clin Cancer Res. 2020;26:3928-3935.
  29. Buza N, English DP, Santin AD, et al. Toward standard HER2 testing of endometrial serous carcinoma: 4-year experience at a large academic center and recommendations for clinical practice. Mod Pathol. 2013;26:1605-1612.
  30. Buza N, Hui P. Marked heterogeneity of HER2/NEU gene amplification in endometrial serous carcinoma. Genes Chromosomes Cancer. 2013;52:1178-1186.
  31. Longacre TA, Broaddus R, Chuang LT, et al. Template for reporting results of biomarker testing of specimens from patients with carcinoma of the endometrium. Arch Pathol Lab Med. 2017;141:1508-1512.
  32. Westphalen CB, Krebs MG, Le Tourneau C, et al. Genomic context of NTRK1/2/3 fusion-positive tumours from a large real-world population. NPJ Precis Oncol. 2021;5:69.
  33. Manea CA, Badiu DC, Ploscaru IC, et al. A review of NTRK fusions in cancer. Ann Med Surg (Lond). 2022;79:103893.
  34. Demetri GD, De Braud F, Drilon A, et al. Updated integrated analysis of the efficacy and safety of entrectinib in patients with NTRK fusion-positive solid tumors. Clin Cancer Res. 2022;28:1302-1312.
  35. Solomon JP, Hechtman JF. Detection of NTRK fusions: merits and limitations of current diagnostic platforms. Cancer Res. 2019;79:3163-3168.
  36. Yu S, Sun Z, Zong L, et al. Clinicopathological and molecular characterization of high-grade endometrial carcinoma with POLE mutation: a single center study. J Gynecol Oncol. 2022;33:e38.
  37. Ghosh DD, Chowdhury RR, Dutta R, et al. In-silico analysis of TCGA data showing multiple POLE-like favourable subgroups overlapping with TP53 mutated endometrial cancer: implications for clinical practice in low and middle-income countries. Gynecol Oncol Rep. 2023:47:101209.
  38. Horeweg N, Nout RA, Jürgenliemk-Schulz IM, et al. Molecular classification predicts response to radiotherapy in the randomized PORTEC-1 and PORTEC-2 trials for early-stage endometrioid endometrial cancer. J Clin Oncol. 2023;41:4369-4380.
  39. Fontanella C, Lepori S, Barcellini A, et al. Is chemotherapy worthwhile in patients with FIGO stage 1B, lymph nodes negative, grade 3 endometrial cancer? Presented at: European Society for Medical Oncology 2017 Congress; September 8-12, 2017. Abstract 977P.
  40. Xiang M, Kidd EA. Survival benefit of radiation in high-risk, early-stage endometrioid carcinoma. J Gynecol Oncol. 2020;31:e39.
  41. Singh N, Piskorz AM, Bosse T, et al. p53 immunohistochemistry is an accurate surrogate for TP53 mutational analysis in endometrial carcinoma biopsies. J Pathol. 2020;336-345.
  42. Murciano-Goroff YR, Schram AM, Rosen EY, et al. Reversion mutations in germline BRCA1/2-mutant tumors reveal a BRCA-mediated phenotype in non-canonical histologies. Nat Commun. 2022;13:7182.