Androgen receptor genotypes predict response to endocrine treatment in breast cancer patients.
Androgen receptor genotypes predict response to endocrine treatment in breast cancer patients.
复制标题
DOI：
10.1038/bjc.2011.441
复制
发表时间：
2011-11-22
影响因子：
8.8
通讯作者：
Jernstrom, H.
中科院分区：
文献类型：
--
作者：
Lundin, K. B.;Henningson, M.;Hietala, M.;Ingvar, C.;Rose, C.;Jernstrom, H.
雄激素受体（AR）在乳腺癌中频繁表达。AR基因型可能影响无病生存率和对内分泌治疗的反应。在2002年至2008年期间，共有634名接受乳腺癌手术的女性被随访至2010年6月30日。六个单倍型标记的单核苷酸多态性的AR，和由此产生的AR双倍型，与乳腺癌患者的特点，肿瘤的特点，无病生存，内分泌治疗的反应进行了检查。发现了五种常见的AR二倍型。十七种罕见变体组合成一个复合组。将得到的6个AR双体型组聚类成两个亚组，A组（n=128）和B组（n=499），每组中具有3个双体型。B组患者的乳房总体积较大（P=0.024），体重指数（BMI）较高（P=0.050），腋窝淋巴结受累较多（P趋势=0.020），组织学分级较高（P趋势=0.031）。在569例浸润性癌症患者中有59例乳腺癌事件，术前未接受治疗。B组患者的无病生存期也短于A组患者（P=0.037）。在雌激素受体α阳性肿瘤的B组患者中，他莫昔芬（TAM）治疗与无病生存期延长相关（P=0.008），而芳香化酶抑制剂（AI）治疗与此无关（P=0.94）。不能根据BMI预测对内分泌治疗的反应，这表明AR双体型的影响超出了较高BMI的影响。一组对TAM有反应但对AI无反应的患者的标志物被确定。如果这一发现得到证实，AR基因分型可能为乳腺癌患者内分泌治疗的选择提供有用的信息。
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 (Ptrend=0.020), and higher histological grade (Ptrend=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.
登录
查看更多内容
绝经后妇女的雄激素受体表达和乳腺癌存活。
DOI：
10.1158/1078-0432.ccr-10-2021
发表时间：
2011-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hu R;Dawood S;Holmes MD;Collins LC;Schnitt SJ;Cole K;Marotti JD;Hankinson SE;Colditz GA;Tamimi RM
通讯作者：
Tamimi RM
影响因子：
3.8
作者：
Fasching, Peter Andreas;Loehberg, Christian R.;Strick, Reiner
通讯作者：
Strick, Reiner
影响因子：
50.5
作者：
Colleoni, M.;Giobbie-Hurder, A.
通讯作者：
Giobbie-Hurder, A.
影响因子：
3.8
作者：
Hietala, Maria;Henningson, Maria;Jernstrom, Helena
通讯作者：
Jernstrom, Helena
影响因子：
45.3
作者：
Dowsett, Mitch;Cuzick, Jack;Peto, Richard
通讯作者：
Peto, Richard