Kamaraju Sailaja, Fowler Amy M, Weil Elizabeth, Wisinski Kari B, Truong Thu H, Lehr Martin, Chaudhary Lubna N, Cheng Yee Chung, Chitambar Christopher R, Rui Hallgeir, Yee Douglas, Lange Carol
Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Division of Hematology-Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Endocrinology. 2021 Aug 1;162(8). doi: 10.1210/endocr/bqab060.
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.
尽管无法治愈，但随着多种靶向和细胞毒性疗法的获批，转移性乳腺癌（MBC）患者的预后有了显著改善。对于激素受体阳性（HR+），即雌激素受体和孕激素受体阳性（ER+/PgR+）且人表皮生长因子受体2阴性（即ERBB2基因未扩增或HER2-）的MBC，目前获批的治疗选择包括姑息性内分泌治疗（ET）、细胞周期蛋白依赖性激酶（CDK 4/6）抑制剂、mTOR抑制剂和PI3激酶抑制剂。大多数治疗针对ER+疾病，而不考虑PgR状态。尽管PgR的存在对于正常和恶性乳腺组织中ER+细胞的增殖至关重要，但目前尚无专门针对PgR的获批治疗方法。最近的文献已在临床前和临床研究中证明了抗孕激素在MBC治疗中的潜力。抗孕激素，包括作为PgR拮抗剂的选择性PgR调节剂（SPRMs），是一类有前景的治疗药物，可用于克服在先前内分泌治疗后发生激活雌激素受体1（ESR1）和磷脂酰肌醇3激酶（PI3K）基因突变的患者的内分泌抵抗。在此，我们总结了PgR和抗孕激素在MBC治疗中的作用。还将简要讨论功能成像的应用、纳入新型抗孕激素的临床试验以及克服内分泌抵抗的潜在治疗组合等其他方面。
