Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, Lund, Sweden.
Br J Cancer. 2011 Nov 22;105(11):1676-83. doi: 10.1038/bjc.2011.441. Epub 2011 Oct 27.
The androgen receptor (AR) is frequently expressed in breast cancers. The AR genotype may affect disease-free survival and response to endocrine therapy.
In all, 634 women undergoing breast cancer surgery between 2002 and 2008 were followed until 30 June 2010. Six haplotype-tagging single-nucleotide polymorphisms in the AR, and the resulting AR diplotypes, were examined in relation to breast cancer patient characteristics, tumour characteristics, disease-free survival, and response to endocrine treatment.
Five common AR diplotypes were found. Seventeen rare variants were combined into a composite group. The resulting six AR diplotype groups were clustered into two subgroups, groups A (n=128) and B (n=499), with three diplotypes in each. Patients in group B had larger total breast volume (P=0.024), higher body mass index (BMI) (P=0.050), more axillary lymph node involvement (P(trend)=0.020), and higher histological grade (P(trend)=0.031). There were 59 breast cancer events in the 569 patients with invasive cancers and no preoperative treatment. Patients in group B also had shorter disease-free survival (P=0.037) than patients in group A. Among patients in group B with oestrogen receptor α positive tumours, tamoxifen (TAM) treatment was associated with longer disease-free survival (P=0.008), while treatment with aromatase inhibitors (AIs) was not (P=0.94). Response to endocrine treatment could not be predicted based on BMI, suggesting that the effect of AR diplotypes went beyond that of a higher BMI.
A marker for a group of patients who responded to TAM, but not to AIs, was identified. If this finding is confirmed, AR genotyping may provide useful information for selection of endocrine treatment of breast cancer patients.
雄激素受体（AR）在乳腺癌中常表达。AR 基因型可能影响无病生存期和对内分泌治疗的反应。
共纳入 2002 年至 2008 年间接受乳腺癌手术的 634 例女性患者，随访至 2010 年 6 月 30 日。分析 AR 中的 6 个单体型标记单核苷酸多态性及其产生的 AR 单体型与乳腺癌患者特征、肿瘤特征、无病生存期和内分泌治疗反应的关系。
发现了 5 种常见的 AR 单体型。将 17 种罕见变体组合成一个复合组。由此产生的 6 个 AR 单体型组聚类为 2 个亚组，A 组（n=128）和 B 组（n=499），每组包含 3 种单体型。B 组患者的总乳房体积更大（P=0.024），体重指数（BMI）更高（P=0.050），腋窝淋巴结受累更多（P（趋势）=0.020），组织学分级更高（P（趋势）=0.031）。在 569 例浸润性癌患者中，有 59 例发生乳腺癌事件，且无术前治疗。B 组患者的无病生存期也较短（P=0.037）。在 B 组中，雌激素受体α阳性肿瘤患者接受他莫昔芬（TAM）治疗的无病生存期更长（P=0.008），而接受芳香化酶抑制剂（AIs）治疗的无病生存期无差异（P=0.94）。不能根据 BMI 预测内分泌治疗的反应，这表明 AR 单体型的影响超出了 BMI 的影响。
鉴定了一组对 TAM 有反应而对 AI 无反应的患者标志物。如果这一发现得到证实，AR 基因分型可能为乳腺癌患者的内分泌治疗选择提供有用的信息。
