PMID- 33735382 OWN - NLM STAT- MEDLINE DCOM- 20211018 LR - 20211018 IS - 1945-7170 (Electronic) IS - 0013-7227 (Linking) VI - 162 IP - 8 DP - 2021 Aug 1 TI - Leveraging Antiprogestins in the Treatment of Metastatic Breast Cancer. LID - bqab060 [pii] LID - 10.1210/endocr/bqab060 [doi] AB - Although incurable, the prognosis for patients with metastatic breast cancer (MBC) has considerably improved with the approvals of multiple targeted and cytotoxic therapies. For hormone receptor-positive (HR+), ie, estrogen receptor and progesterone receptor positive (ER+/PgR+) and human epidermal growth factor receptor-2 negative (ie, ERBB2 gene nonamplified or HER2-) MBC, current approved treatment options include palliative endocrine therapy (ET), cyclin-dependent kinase (CDK 4/6) inhibitors, mTOR inhibitors, and PI3 kinase inhibitors. Most treatments target ER+ disease regardless of PgR status. Although the presence of PgR is crucial for ER+ cell proliferation in both normal and malignant mammary tissue, currently, there are no approved treatments that specifically target PgR. Recent literature has demonstrated the potential of antiprogestins in the treatment of MBC both in preclinical and clinical studies. Antiprogestins, including selective PgR modulators (SPRMs) that act as PgR antagonists, are a promising class of therapeutics for overcoming endocrine resistance in patients who develop activating estrogen receptor 1 (ESR1) and phosphatidylinositol 3-kinase (PI3K) gene mutations after prior endocrine therapy. Herein, we summarize the role of PgR and antiprogestins in the treatment of MBC. Other aspects on the use of functional imaging, clinical trials incorporating novel antiprogestins, and potential treatment combinations to overcome endocrine resistance will be briefly discussed. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Kamaraju, Sailaja AU - Kamaraju S AUID- ORCID: 0000-0003-3031-9269 AD - Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA. FAU - Fowler, Amy M AU - Fowler AM AD - Division of Hematology-Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. AD - Division of Hematology-Oncology Medical College of Wisconsin, Cancer Center, 4th Fl Administrative Offices, Watertown Plank Road, Milwaukee, WI 53226, USA. FAU - Weil, Elizabeth AU - Weil E AD - Froedtert Health, Cancer Center, Milwaukee, WI 53226, USA. FAU - Wisinski, Kari B AU - Wisinski KB AD - Division of Hematology-Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. AD - Division of Hematology-Oncology Medical College of Wisconsin, Cancer Center, 4th Fl Administrative Offices, Watertown Plank Road, Milwaukee, WI 53226, USA. FAU - Truong, Thu H AU - Truong TH AD - Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA. FAU - Lehr, Martin AU - Lehr M AD - Context Therapeutics, Philadelphia, PA 19104, USA. FAU - Chaudhary, Lubna N AU - Chaudhary LN AD - Division of Hematology-Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. AD - Division of Hematology-Oncology Medical College of Wisconsin, Cancer Center, 4th Fl Administrative Offices, Watertown Plank Road, Milwaukee, WI 53226, USA. FAU - Cheng, Yee Chung AU - Cheng YC AD - Division of Hematology-Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. AD - Division of Hematology-Oncology Medical College of Wisconsin, Cancer Center, 4th Fl Administrative Offices, Watertown Plank Road, Milwaukee, WI 53226, USA. FAU - Chitambar, Christopher R AU - Chitambar CR AD - Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA. FAU - Rui, Hallgeir AU - Rui H AD - Pathology and Laboratory Medicine, Medical College of Wisconsin , Milwaukee, WI 53226, USA. FAU - Yee, Douglas AU - Yee D AUID- ORCID: 0000-0002-3387-4009 AD - Division of Hematology-Oncology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA. FAU - Lange, Carol AU - Lange C AD - Division of Hematology-Oncology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Antineoplastic Agents) RN - 0 (Receptors, Progesterone) SB - IM MH - Animals MH - Antineoplastic Agents/pharmacology/*therapeutic use MH - Breast Neoplasms/*drug therapy/metabolism MH - Clinical Trials as Topic MH - Humans MH - Receptors, Progesterone/*antagonists & inhibitors/metabolism OTO - NOTNLM OT - antiprogestins OT - metastatic breast cancer OT - progesterone receptor EDAT- 2021/03/19 06:00 MHDA- 2021/10/21 06:00 CRDT- 2021/03/18 17:46 PHST- 2020/11/17 00:00 [received] PHST- 2021/03/19 06:00 [pubmed] PHST- 2021/10/21 06:00 [medline] PHST- 2021/03/18 17:46 [entrez] AID - 6178343 [pii] AID - 10.1210/endocr/bqab060 [doi] PST - ppublish SO - Endocrinology. 2021 Aug 1;162(8):bqab060. doi: 10.1210/endocr/bqab060.