Androgen receptor: discoveries in breast cancer clinical practice

doi:10.3877/cma.j.issn.1674-0785.2022.11.001

Abstract

Abstract:

Breast cancer is the malignant tumor with the highest incidence in the world. At present, breast cancer treatment has entered the era of classified treatment guided by molecular markers. Androgen receptor (AR) is a commonly expressed molecular marker in breast cancer, which regulates breast cancer cell activities. In clinical practice, AR expression has an appreciated correlation with the prognosis of breast cancer patients, and AR-targeted therapy and related combination therapies are under investigation. This article summarizes the application of AR in breast cancer from the aspects of mechanism, expression and clinical value, and related therapies, by reviewing the relevant literature in recent years.

Key words: Breast neoplasms, Breast cancer, Molecular subtype, Androgen receptor, Prognosis, Androgen receptor targeted therapy

Jiayi Li, Hong Zhang, Jingming Ye, Yinhua Liu, Ling Xu, Shuang Zhang. Androgen receptor: discoveries in breast cancer clinical practice[J]. Chinese Journal of Clinicians(Electronic Edition), 2022, 16(11): 1031-1038.

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药物	药物机制	研究代码	入组人群	治疗方案	研究结果
比卡鲁胺	第一代非甾体AR拮抗剂，通过干扰雄激素-AR复合物与DNA结合产生作用。	NCT00468715^［60］	ER/PR阴性晚期乳腺癌，AR＞10%（n=26）	比卡鲁胺	6月CBR 19%，中位PFS 12周
比卡鲁胺	第一代非甾体AR拮抗剂，通过干扰雄激素-AR复合物与DNA结合产生作用。	NCT02910050^［61］	接受过AI治疗的ER+AR+HER-2-转移性乳腺癌（n=18）	比卡鲁胺+AI	6月CBR 16.7%，中位PFS 2.7个月
恩杂鲁胺	第二代非甾体AR拮抗剂，通过干扰雄激素-AR复合物向细胞核内转移、染色质结合、调控因子发挥作用。	NCT01889238^［62］	局部进展和远处转移AR阳性（＞0%）TNBC（n=78）	恩杂鲁胺	16周CBR 25%，中位PFS 2.9个月，中位OS 12.7个月；AR≥10% 亚组：16周CBR 33%，中位PFS 3.3个月，中位OS 17.6个月
		NCT02457910 （TBCRC032）^［63］	AR≥10%的转移性TNBC（n=12）	恩杂鲁胺+taselisib	16周CBR 35.7%，中位PFS 3.4个月
		NCT02007512^［64］	HR+HER-2正常晚期/转移性乳腺癌（n=247）	实验组：依西美坦+恩杂鲁胺，对照组：依西美坦+安慰剂	既往无内分泌治疗组：24周CBR 62%比45%，PFS 11.8个月比5.8个月；既往内分泌治疗组：24周CBR 20%比32%，PFS 3.6个月比3.9个月
		NCT02091960^［65］	HER-2+AR+乳腺癌（n=89）	恩杂鲁胺+曲妥珠单抗	24周CBR 24%，中位PFS 3.4个月
阿比特龙	CYP17A酶抑制剂，通过抑制CYP17A酶活性阻断DHT生成，目前被用于去势抵抗性前列腺癌治疗。	NCT01381874^［66］	ER+晚期乳腺癌（n=297）	AA组：阿比特龙，AAE组：阿比特龙+依西美坦，E组依西美坦	PFS：AA组3.7个月，AAE组4.5个月，E组3.7个月，无显著差异
阿比特龙	CYP17A酶抑制剂，通过抑制CYP17A酶活性阻断DHT生成，目前被用于去势抵抗性前列腺癌治疗。	NCT01842321^［67］	远处转移或局部进展的AR+（≥10%）TNBC（n=30）	阿比特龙	6个月CBR 20.0%，ORR 6.7%，中位PFS 2.8个月
Enobosarm	SARM，与AR复合后向细胞核转移后，作为转录调节剂并募集辅助因子和核心蛋白，调节相关转录反应，产生AR激动作用。	NCT 02971761^［68］	AR+（≥10%）远处转移TNBC（n=18）	Enobosarm+帕博利珠单抗	16周CBR 25%，中位PFS 2.6个月，OS 25.5个月

药物	药物机制	研究代码	入组人群	治疗方案	研究结果
比卡鲁胺	第一代非甾体AR拮抗剂，通过干扰雄激素-AR复合物与DNA结合产生作用。	NCT00468715^［60］	ER/PR阴性晚期乳腺癌，AR＞10%（n=26）	比卡鲁胺	6月CBR 19%，中位PFS 12周
比卡鲁胺	第一代非甾体AR拮抗剂，通过干扰雄激素-AR复合物与DNA结合产生作用。	NCT02910050^［61］	接受过AI治疗的ER+AR+HER-2-转移性乳腺癌（n=18）	比卡鲁胺+AI	6月CBR 16.7%，中位PFS 2.7个月
恩杂鲁胺	第二代非甾体AR拮抗剂，通过干扰雄激素-AR复合物向细胞核内转移、染色质结合、调控因子发挥作用。	NCT01889238^［62］	局部进展和远处转移AR阳性（＞0%）TNBC（n=78）	恩杂鲁胺	16周CBR 25%，中位PFS 2.9个月，中位OS 12.7个月；AR≥10% 亚组：16周CBR 33%，中位PFS 3.3个月，中位OS 17.6个月
		NCT02457910 （TBCRC032）^［63］	AR≥10%的转移性TNBC（n=12）	恩杂鲁胺+taselisib	16周CBR 35.7%，中位PFS 3.4个月
		NCT02007512^［64］	HR+HER-2正常晚期/转移性乳腺癌（n=247）	实验组：依西美坦+恩杂鲁胺，对照组：依西美坦+安慰剂	既往无内分泌治疗组：24周CBR 62%比45%，PFS 11.8个月比5.8个月；既往内分泌治疗组：24周CBR 20%比32%，PFS 3.6个月比3.9个月
		NCT02091960^［65］	HER-2+AR+乳腺癌（n=89）	恩杂鲁胺+曲妥珠单抗	24周CBR 24%，中位PFS 3.4个月
阿比特龙	CYP17A酶抑制剂，通过抑制CYP17A酶活性阻断DHT生成，目前被用于去势抵抗性前列腺癌治疗。	NCT01381874^［66］	ER+晚期乳腺癌（n=297）	AA组：阿比特龙，AAE组：阿比特龙+依西美坦，E组依西美坦	PFS：AA组3.7个月，AAE组4.5个月，E组3.7个月，无显著差异
阿比特龙	CYP17A酶抑制剂，通过抑制CYP17A酶活性阻断DHT生成，目前被用于去势抵抗性前列腺癌治疗。	NCT01842321^［67］	远处转移或局部进展的AR+（≥10%）TNBC（n=30）	阿比特龙	6个月CBR 20.0%，ORR 6.7%，中位PFS 2.8个月
Enobosarm	SARM，与AR复合后向细胞核转移后，作为转录调节剂并募集辅助因子和核心蛋白，调节相关转录反应，产生AR激动作用。	NCT 02971761^［68］	AR+（≥10%）远处转移TNBC（n=18）	Enobosarm+帕博利珠单抗	16周CBR 25%，中位PFS 2.6个月，OS 25.5个月

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