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PROTACs in MBC

CE / CME

PROTAC ER Degraders in ER-Positive/HER2-Negative MBC Progressing After Endocrine Therapy: Current Treatment Landscape and Addressing Unmet Needs

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Pharmacists: 1.00 contact hour (0.1 CEUs)

Physicians: maximum of 1.00 AMA PRA Category 1 Credit

Nurse Practitioners/Nurses: 1.00 Nursing contact hour

Released: March 12, 2026

Expiration: September 11, 2026

Activity

Progress
1 2 3
Course Completed

References

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  2. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: breast cancer.  v.1.2026. nccn.org. Accessed March 5, 2026.
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  9. Talazoparib [prescribing information]. New York, NY; Pfizer; 2025.
  10. Sukhun SA, Temin S, Barrios CH, et al. Systemic treatment of patients with metastatic breast cancer: ASCO resource–stratified guideline. JCO Global Oncology. 2024:e2300285.
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  13. Slamon DJ, Neven P, Chia S, et al. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol. 2018;36:2465-2472.
  14. ‌Tripathy D, Im SA, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19:904-915.
  15. ‌Johnston S, Martin M, Di Leo A, et al. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer. 2019;5:5.
  16. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer: results from the randomized phase III EMERALD trial. J Clin Oncol. 2022;40:3246-3256.
  17. ‌Jhaveri KL, Neven P, Casalnuovo ML, et al. Imlunestrant with or without abemaciclib in advanced breast cancer: updated efficacy results from the phase III EMBER-3 trial. Ann Oncol. 2025;[Epub ahead of print].
  18. Burstein HJ. Systemic therapy for estrogen receptor-positive, HER2-negative breast cancer. N Engl J Med. 2020;383:2557.
  19. Chumsri S, Howes T, Bao T, et al. Aromatase, aromatase inhibitors, and breast cancer. J Steroid Biochem Mol Biol. 2011;125:13-22.
  20. Burstein HJ, DeMichele A, Somerfield MR, et al. Testing for ESR1 mutations to guide therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2023;41:3423-3425.
  21. Cardoso F, Paluch-Shimon S, Schumacher-Wulf E, et al. 6th and 7th international consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7). Breast. 2024;76:103756.
  22. Jhavery KL, Neven P, Casalnuovo, et al. Imlunestrant with or without abemaciclib in advanced breast cancer (ABC): updated efficacy results from the phase III EMBER-3 trial. SABCS 2025 Presented at: 2025 San Antonio Breast Cancer Symposium Annual Conference. December 9-12, 2025. Abstract GS3-08
  23. Mayer E, Tolaney S, Martin M, et al. Giredestrant (GIRE), an oral selective oestrogen receptor (ER) antagonist and degrader, + everolimus (E) in patients (pts) with ER-positive, HER2-negative advanced breast cancer (ER+, HER2- ABC) previously treated with a CDK4/6 inhibitor (i): primary results of the phase III evERA BC trial. Presented at: 2025 European Society for Medical Oncology Breast Cancer Annual Conference. October 17-21, Berlin, Germany. Abstract LBA16.
  24. Rugo HS, Tolaney SM, Jhaveri KL, et al. Clinical and biomarker subgroup analysis of evERA Breast Cancer: a phase III trial of giredestrant plus everolimus in patients with estrogen receptor-positive, HER2-negative advanced breast cancer previously treated with a CDK4/6 inhibitor. Presented at: 2025 San Antonio Breast Cancer Symposium Annual Conference. December 9-12, 2025. Abstract GS3-09.
  25. Bramlet KS and Burris TP. Effects of selective estrogen receptor modulators (SERMs) on coactivator nuclear receptor (NR) box binding to estrogen receptor. Mol Genet Metab. 2002;76:225-233.
  26. Hanker AB, Sudhan, and Arteaga CL. Overcoming endocrine resistance in breast cancer. Cancer Cell. 2020;37:496-513.
  27. Nathan MR, Schmid P. A review of fulvestrant in breast cancer. Oncol Ther. 2017;5:17-29.
  28. Dorso M, Kuhlberg C, Wang X, et al. Vepdegestrant, a PROteolysis targeting chimera (PROTAC) estrogen receptor (ER) degrader, induces greater ER degradation and antitumor activity relative to selective ER degraders (SERDs) in preclinical ER+ breast cancer models. Presented at: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. October 22-26, 2025; Abstract nrB115.
  29. Gough SM, Flanagan JJ, The J, et al. Oral estrogen receptor PROTAC vepdegestrant (ARV-471) is highly efficacious as monotherapy and in combination with CDK4/6 or PI3L/mTOR pathway inhibitors in preclinical ER+ breast cancer models. Clin Cancer Res. 2024;30:3549-3563.
  30. Hurvitz S, Schott AF, Ma C, et al. GS3-03 ARV-471, a PROTAC® estrogen receptor (ER) degrader in advanced ER-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer: phase 2 expansion (VERITAC) of a phase 1/2 study. Presented at: 2022 San Antonio Breast Cancer Symposium Annual Conference. December 6–10, 2022. Abstract GS3-03
  31. Hamilton EP, Hurvitz SA, McAndrew NP, et al. Vepdegestrant, a proteolysis targeting chimera (PROTAC) estrogen receptor (ER) degrader, plus palbociclib (palbo) in ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer: Updated phase Ib cohort results. Presented at: 2024 European Society for Medical Oncology Breast Cancer Annual Conference. May 15-17, 2024. Abstract 218P.
  32. Campone M, De Laurentiis M, Jhaveri K, et al. Vepdegestrant, a PROTAC estrogen receptor degrader, in advanced breast cancer. N Engl J Med. 2025;393:556-568.
  33. Hamilton EP, De Laurentiis M, Jhaveri KL, et al. Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: Results of the global, randomized, phase 3 VERITAC-2 study. Presented at: 2025 American Society of Clinical Oncology Annual Conference. May 30-June 3, 2025; Abstract LBA1000.
  34. Hamilton E, Kim SY, Fan J, et al.  AC699, a novel chimeric estrogen receptor degrader, in a phase I study in breast cancer. Presented at: 2024 European Society for Medical Oncology Breast Cancer Annual Conference. September 13–17, 2024, Barcelona, Spain. Abstract 6059.