Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer.
Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer.
复制标题
DOI：
10.1158/1078-0432.ccr-12-3327
复制
发表时间：
2013-10-01
期刊：
影响因子：
--
通讯作者：
Translational Breast Cancer Research Consortium (TBCRC 011)
中科院分区：
文献类型：
--
作者：
Gucalp A;Tolaney S;Isakoff SJ;Ingle JN;Liu MC;Carey LA;Blackwell K;Rugo H;Nabell L;Forero A;Stearns V;Doane AS;Danso M;Moynahan ME;Momen LF;Gonzalez JM;Akhtar A;Giri DD;Patil S;Feigin KN;Hudis CA;Traina TA;Translational Breast Cancer Research Consortium (TBCRC 011)
激素受体阴性乳腺癌患者通常不会从内分泌靶向治疗中受益。然而，预测具有雄激素受体（AR）表达的亚群对抗雄激素疗法有反应。这项 II 期研究探讨了比卡鲁胺治疗 AR 阳性、雌激素受体 (ER) 和孕激素受体 (PgR) 阴性的转移性乳腺癌。对 ER/PgR 阴性晚期乳腺癌患者的肿瘤进行集中 AR 检测 [免疫组织化学 (IHC) > 10% 核染色视为阳性]。如果原发部位或转移部位呈阳性，患者就有资格接受 AR 拮抗剂比卡鲁胺，剂量为每天 150 毫克。主要终点临床获益率 (CBR) 定义为表现出完全缓解 (CR)、部分缓解 (PR) 或疾病稳定 (SD) > 6 个月的患者总数；次要终点包括无进展生存期（PFS）和毒性。相关研究包括测量循环内分泌标志物和基底细胞样乳腺癌的 IHC 替代物。在 424 名 ER/PgR 阴性乳腺癌患者中，12% 的患者检测结果呈 AR 阳性。比卡鲁胺的 6 个月 CBR 为 19%[95% 置信区间 (CI)，7%–39%]。中位 PFS 为 12 周（95% CI，11-22 周）。比卡鲁胺耐受性良好，未观察到 4/5 级治疗相关不良事件。本试验筛选的 ER/PgR 阴性乳腺癌患者中有 12% 表达 AR。使用比卡鲁胺观察到的 CBR 为 19%，这证明了微毒雄激素阻断在选定的 ER/PgR 阴性、AR 阳性乳腺癌患者组中的有效性。
Patients with hormone receptor–negative breast cancer generally do not benefit from endocrine-targeted therapies. However, a subset with androgen receptor (AR) expression is predicted to respond to antiandrogen therapies. This phase II study explored bicalutamide in AR-positive, estrogen receptor (ER), and progesterone receptor (PgR)-negative metastatic breast cancer. Tumors from patients with ER/PgR-negative advanced breast cancer were tested centrally for AR [immunohistochemistry (IHC) > 10% nuclear staining considered positive]. If either the primary or a metastatic site was positive, patients were eligible to receive the AR antagonist bicalutamide at a dose of 150 mg daily. Clinical benefit rate (CBR), the primary endpoint, was defined as the total number of patients who show a complete response (CR), partial response (PR), or stable disease (SD) > 6 months; secondary endpoints included progression-free survival (PFS) and toxicity. Correlative studies included measurement of circulating endocrine markers and IHC surrogates for basal-like breast cancer. Of 424 patients with ER/PgR-negative breast cancer, 12% tested AR-positive. The 6-month CBR was19%[95% confidence interval (CI), 7%–39%]for bicalutamide. The median PFS was 12 weeks (95% CI, 11–22 weeks). Bicalutamide was well-tolerated with no grade 4/5 treatment-related adverse events observed. AR was expressed in 12% of patients with ER/PgR-negative breast cancer screened for this trial. The CBR of 19% observed with bicalutamide shows proof of principle for the efficacy of minimally toxic androgen blockade in a select group of patients with ER/PgR-negative, AR-positive breast cancer.