Saray Seray, Yılmaz Tufan, Kanmaz Hüseyin, İriağaç Yakup
Department of Medical Oncology, Balikesir Ataturk City Hospital, Balikesir 10100, Turkey.
Department of Pathology, Balikesir Ataturk City Hospital, Balikesir 10100, Turkey.
Medicina (Kaunas). 2025 Aug 14;61(8):1464. doi: 10.3390/medicina61081464.
The effect of AR expression on prognosis in hormone receptor-positive her2-negative breast cancer is controversial. There are studies showing that AR is a treatment target, a mechanism of resistance to endocrine treatments, and a prognostic indicator in these patients whose standard treatment is a CDK 4/6 inhibitor added to endocrine treatment. We aimed to investigate the effect of AR, the AR/ER ratio, and the AR/PR ratio on CDK4/6 inhibitor treatment response in breast cancer, as well as their effects on PFS, and to validate the hypothesis that AR is a target for research. Patients who were diagnosed with metastatic hormone receptor-positive her2-negative breast cancer and received cdk4/6 inhibitor + aromatase inhibitor in first-line therapy were included in this study conducted at Balıkesir Atatürk City Hospital. The tru-cut biopsy samples of the patients were evaluated immunohistochemically for AR, ER, and PR. Kaplan-Meier analysis was used to calculate the estimated median survival in PFS analyses, and the variables were compared with the Log-Rank test. Receiver Operating Characteristic (ROC) analysis was applied to determine the ideal cut-off. Cox regression analysis was used in univariate survival models, and the multivariate model was established with the "Forward: Likelihood Ratio (LR)" method. Hazard ratios (HRs) were also calculated as 95% confidence intervals (95% CIs). A value below 0.05 was accepted for statistical significance. In total, 41 patients were included in the study, and 73% (n = 30) of the patients were AR-positive. Increased AR (HR 1.014; 95% CI: 1.002-1.026; = 0.023) was an unfavorable prognostic indicator. In our study, being ≥55 years old, being postmenopausal, not having visceral metastasis, having a non-IDC histology, having a low AR level (<50%), having an AR/ER ratio < 0.74, and having an AR/PR ratio < 1.00 were found to be associated with longer PFS. All factors were evaluated with univariate Cox regression analysis. Increasing AR (HR 1.014; 95% CI: 1.002-1.026; = 0.023) was an unfavorable prognostic marker. Having an AR/ER ratio ≥ 0.74 (HR: 2.522; 95% CI: 1.004-6.336; = 0.049) and having AR/PR ≥ 1 (HR: 2.659; 95% CI: 1.029-6.869; = 0.043) were negative prognostic indicators. Our results were consistent with the literature and demonstrated the value of the androgen receptor as a therapeutic target, a mechanism explaining resistance to endocrine therapy, and an adverse prognostic indicator for creating resistance to endocrine therapy in breast cancer.
雄激素受体（AR）表达对激素受体阳性、人表皮生长因子受体2（HER2）阴性乳腺癌预后的影响存在争议。有研究表明，在这些标准治疗为在内分泌治疗基础上加用细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂的患者中，AR是一个治疗靶点、内分泌治疗耐药的一种机制以及一个预后指标。我们旨在研究AR、AR/雌激素受体（ER）比值和AR/孕激素受体（PR）比值对乳腺癌CDK4/6抑制剂治疗反应的影响，以及它们对无进展生存期（PFS）的影响，并验证AR是一个研究靶点的假设。在巴勒克埃西尔阿塔图尔克市立医院进行的这项研究纳入了一线治疗中被诊断为转移性激素受体阳性、HER2阴性乳腺癌且接受CDK4/6抑制剂+芳香化酶抑制剂治疗的患者。对患者的粗针穿刺活检样本进行AR、ER和PR的免疫组织化学评估。在PFS分析中，采用Kaplan-Meier分析计算估计的中位生存期，并使用对数秩检验比较变量。应用受试者工作特征（ROC）分析确定理想的截断值。在单变量生存模型中使用Cox回归分析，并采用“向前：似然比（LR）”方法建立多变量模型。还计算了风险比（HRs）及其95%置信区间（95% CIs）。P值低于0.05被认为具有统计学意义。本研究共纳入41例患者，73%（n = 30）的患者AR呈阳性。AR升高（HR 1.014；95% CI：1.002 - 1.026；P = 0.023）是一个不良预后指标。在我们的研究中，发现年龄≥55岁、绝经后、无内脏转移、组织学类型非浸润性导管癌（IDC）、AR水平低（<50%）、AR/ER比值<0.74以及AR/PR比值<1.00与更长的PFS相关。所有因素均通过单变量Cox回归分析进行评估。AR升高（HR 1.014；95% CI：1.002 - 1.026；P = 0.023）是一个不良预后标志物。AR/ER比值≥0.74（HR：2.522；95% CI：1.004 - 6.336；P = 0.049）和AR/PR≥1（HR：2.659；95% CI：1.029 - 6.869；P = 0.043）是阴性预后指标。我们的结果与文献一致，并证明了雄激素受体作为治疗靶点、解释内分泌治疗耐药的一种机制以及乳腺癌内分泌治疗耐药的不良预后指标的价值。
