血清卵泡刺激素和黄体生成素水平与克氏综合征患者乳腺癌发生风险的相关性
|
摘要
目的探讨血清卵泡刺激素(FSH)和黄体生成素(LH)水平对克氏综合征(KS)患者5年内乳腺癌发病的预测价值。方法选取2011年6月至2013年6月湖北省潜江市中心医院收治的KS患者55例,根据5年随访乳腺癌发病与否分为乳腺癌组(17例)及对照组(38例),比较2组患者雄激素维持治疗剂量、服药时间、服药依从性(Morisky评分)以及治疗前和睾酮水平稳定后的血清性激素水平。应用Cox回归分析KS患者5年内乳腺癌发病的独立危险因素,应用受试者工作特征曲线评估各指标预测乳腺癌的诊断效能。结果 2组KS患者雄激素维持剂量、服药时间和Morisky评分比较差异均无统计学意义(均P> 0. 05)。治疗前,乳腺癌组患者血清FSH及LH水平均高于对照组,差异均有统计学意义(均P <0. 05);治疗后,2组患者血清FSH及LH水平均低于治疗前,且乳腺癌组均高于对照组,差异均有统计学意义(均P <0. 05)。Cox回归分析结果表明,治疗前FSH及LH水平是KS患者5年内乳腺癌发病的独立危险因素(均P <0. 05)。受试者工作特征曲线分析结果表明,治疗前FSH及LH水平预测KS患者5年内乳腺癌发病的曲线下面积分别为0. 796、0. 797,截断值分别为30. 663 U/L和12. 614 U/L,二指标联合预测的曲线下面积为0. 907,诊断效能显著优于治疗前FSH及LH单独预测(P=0. 047、0. 045),且联合预测的敏感度(82. 35%)也显著优于二者单独预测(均P <0. 05)。结论治疗前血清FSH及LH水平可有效预测KS患者5年内乳腺癌的发病风险,二者水平越高,5年内乳腺癌的发病风险越大。
Objective To investigate the predictive values of serum follicle stimulating hormone( FSH and luteinizing hormone( LH) for the 5-year incidence of breast cancer in patients with Klinefelter syndrome( KS).Methods From June 2011 to June 2013,55 KS patients admitted to Qianjiang Central Hospital,Hubei Province were followed up for 5 years. According to the occurrence of breast cancer during follow-up,they were divided into breast cancer group( 17 cases) and control group( 38 cases). Maintenance dose of androgen,duration of medication,medication compliance( Morisky score),serum levels of sex hormone before and after treatment were recorded.Independent risk factors of breast cancer were analyzed by Cox regression. Receiver operating characteristic( ROC)curve was used to evaluate the diagnostic efficacy of indexes in predicting breast cancer. Results There were no statistical differences of androgen maintenance dose,duration of medication and Morisky score between groups( P > 0. 05). Levels of serum FSH and LH in breast cancer group were significantly higher than those in control group before treatment( both P < 0. 05). After treatment,levels of serum FSH and LH significantly decreased in both groups; the levels in breast cancer group were significantly higher than those control group( all P < 0. 05).Cox regression analysis showed that FSH and LH levels before medication were independent risk factors of the5-year incidence of breast cancer( P < 0. 05). ROC curve showed that areas under curve of FSH and LH in predicting the 5-year incidence of breast cancer were 0. 796 and 0. 797; the optimal cut-off points were 30. 663 U/L and 12. 614 U/L; area under curve of combined diagnosis of FSH and LH was 0. 907; the diagnostic efficacy of combined diagnosis was significantly higher than that of separate detections( P = 0. 047,0. 045); the sensitivity of combined diagnosis( 82. 35%) was significantly higher than that of separate detections( both P < 0. 05).Conclusion Elevated pretherapy levels of serum FSH and LH indicate high risk of breast cancer in 5 years in patients diagnosed of KS.
Objective To investigate the predictive values of serum follicle stimulating hormone( FSH and luteinizing hormone( LH) for the 5-year incidence of breast cancer in patients with Klinefelter syndrome( KS).Methods From June 2011 to June 2013,55 KS patients admitted to Qianjiang Central Hospital,Hubei Province were followed up for 5 years. According to the occurrence of breast cancer during follow-up,they were divided into breast cancer group( 17 cases) and control group( 38 cases). Maintenance dose of androgen,duration of medication,medication compliance( Morisky score),serum levels of sex hormone before and after treatment were recorded.Independent risk factors of breast cancer were analyzed by Cox regression. Receiver operating characteristic( ROC)curve was used to evaluate the diagnostic efficacy of indexes in predicting breast cancer. Results There were no statistical differences of androgen maintenance dose,duration of medication and Morisky score between groups( P > 0. 05). Levels of serum FSH and LH in breast cancer group were significantly higher than those in control group before treatment( both P < 0. 05). After treatment,levels of serum FSH and LH significantly decreased in both groups; the levels in breast cancer group were significantly higher than those control group( all P < 0. 05).Cox regression analysis showed that FSH and LH levels before medication were independent risk factors of the5-year incidence of breast cancer( P < 0. 05). ROC curve showed that areas under curve of FSH and LH in predicting the 5-year incidence of breast cancer were 0. 796 and 0. 797; the optimal cut-off points were 30. 663 U/L and 12. 614 U/L; area under curve of combined diagnosis of FSH and LH was 0. 907; the diagnostic efficacy of combined diagnosis was significantly higher than that of separate detections( P = 0. 047,0. 045); the sensitivity of combined diagnosis( 82. 35%) was significantly higher than that of separate detections( both P < 0. 05).Conclusion Elevated pretherapy levels of serum FSH and LH indicate high risk of breast cancer in 5 years in patients diagnosed of KS.
引文
[1]Groth KA,Skakkebk A,Hst C,et al.Clinical review:Klinefelter syndrome-a clinical update[J].J Clin Endocrinol Metab,2013,98(1):20-30.DOI:10.1210/jc.2012-2382.
[2]Vallabhajosyula R,Rajangam S,C L.Association of parental origin with clinical profile in klinefelter syndrome[J].J Clin Diagn Res,2015,9(3):GC01-3.DOI:10.7860/JCDR/2015/8291.5612.
[3]Ando M,Yamaguchi K,Chiba K,et al.Outcome of microdissection testicular sperm extraction in azoospermic patients with Klinefelter syndrome and other sex-chromosomal anomalies[J].Syst Biol Reprod Med,2013,59(4):210-213.DOI:10.3109/19396368.2012.733059.
[4]Brinton LA,Carreon JD,Gierach GL,et al.Etiologic factors for male breast cancer in the U.S.Veterans Affairs medical care system database[J].Breast Cancer Res Treat,2010,119(1):185-192.DOI:10.1007/s10549-009-0379-0.
[5]Chang S,Skakkebk A,Trolle C,et al.Anthropometry in Klinefelter syndrome-multifactorial influences due to CAG length,testosterone treatment and possibly intrauterine hypogonadism[J].J Clin Endocrinol Metab,2015,100(3):E508-517.DOI:10.1210/jc.2014-2834.
[6]中国抗癌协会乳腺癌专业委员会.中国抗癌协会乳腺癌诊治指南与规范(2015版)[J].中国癌症杂志,2015,25(9):692-754.Professional Committee on Breast Cancer,China Anti-Cancer Association.Guidelines and specifications for diagnosis and treatment of breast cancer of China Anti-Cancer Association(2015Edition)[J].China Oncology,2015,25(9):692-754.
[7]薛会丽,林丹玫,陈雪美,等.1891例男性不育患者的细胞遗传学分析[J].中华医学遗传学杂志,2017,34(5):772-774.DOI:10.3760/cma.j.issn.1003-9406.2017.05.033.Xue HL,Lin DM,Chen XM,et al.Cytogenetic analysis of 1891male infertility patients[J].Chinese Journal of Medical Genetics,2017,34(5):772-774.DOI:10.3760/cma.j.issn.1003-9406.2017.05.033.
[8]Chen X,Williams-Burris SM,Mc Clusky R,et al.The Sex Chromosome Trisomy mouse model of XXY and XYY:metabolism and motor perform ance[J].Biol Sex Differ,2013,4(1):15.DOI:10.1186/2042-6410-4-15.
[9]Overvad S,Bay K,Bojesen A,et al.Low INSL3 in Klinefelter syndrome is related to osteocalcin,testosterone treatment and body composition,as well as measures of the hypothalamic-pituitarygonadal axis[J].Andrology,2014,2(3):421-427.DOI:10.1111/j.2047-2927.2014.00204.x.
[10]Ozveri H,Kayabasoglu F,Demirel C,et al.Outcomes of microdissection TESE in patients with non-mosaic Klinefelter's syndrome without hormonal treatment[J].Int J Fertil Steril,2015,8(4):421-428.
[11]季兴哲,周梁,孙建华,等.应用ROC曲线评价血清FSH、LH及T在非嵌合型克氏综合征诊断中的价值[J].中国优生与遗传杂志,2017,25(11):64-66.DOI:10.13404/j.cnki.cjbhh.2017.11.020.Ji XZ,Zhou L,Sun JH,et al.Evaluation of serum FSH,LH and T in the diagnosis of non-chimeric Kirschner syndrome by ROCcurve[J].Chinese Journal of Birth Health&Heredity,2017,25(11):64-66.DOI:10.13404/j.cnki.cjbhh.2017.11.020.
[12]Busch AS,Tüttelmann F,Zitzmann M,et al.The FSHB-211G>Tvariant attenuates serum FSH levels in the supraphysiological gonadotropin setting of Klinefelter syndrome[J].Eur J Hum Genet,2015,23(5):700-703.DOI:10.1038/ejhg.2014.142.
[13]Cabrol S,Ross JL,Fennoy I,et al.Assessment of Leydig and Sertoli cell functions in infants with nonmosaic Klinefelter syndrome:insulin-like peptide 3 levels are normal and positively correlated with LH levels[J].J Clin Endocrinol Metab,2011,96(4):E746-753.DOI:10.1210/jc.2010-2103.
[14]Fentiman IS.The biology of male breast cancer[J].Breast,2018,38:132-135.DOI:10.1016/j.breast.2018.01.001.
[15]Kerdivel G,Boudot A,Habauzit D,et al.Activation of the MKL1/actin signaling pathway induces hormonal escape in estrogen-responsivebreast cancer cell lines[J].Mol Cell Endocrinol,2014,390(1-2):34-44.DOI:10.1016/j.mce.2014.03.009.
[16]Inci M,Akgul O,Baydilli N,et al.Increased femoral cartilage thickness in patients with Klinefelter syndrome[J].Am J Mens Health,2013,7(1):54-57.DOI:10.1177/1557988312458449.
[2]Vallabhajosyula R,Rajangam S,C L.Association of parental origin with clinical profile in klinefelter syndrome[J].J Clin Diagn Res,2015,9(3):GC01-3.DOI:10.7860/JCDR/2015/8291.5612.
[3]Ando M,Yamaguchi K,Chiba K,et al.Outcome of microdissection testicular sperm extraction in azoospermic patients with Klinefelter syndrome and other sex-chromosomal anomalies[J].Syst Biol Reprod Med,2013,59(4):210-213.DOI:10.3109/19396368.2012.733059.
[4]Brinton LA,Carreon JD,Gierach GL,et al.Etiologic factors for male breast cancer in the U.S.Veterans Affairs medical care system database[J].Breast Cancer Res Treat,2010,119(1):185-192.DOI:10.1007/s10549-009-0379-0.
[5]Chang S,Skakkebk A,Trolle C,et al.Anthropometry in Klinefelter syndrome-multifactorial influences due to CAG length,testosterone treatment and possibly intrauterine hypogonadism[J].J Clin Endocrinol Metab,2015,100(3):E508-517.DOI:10.1210/jc.2014-2834.
[6]中国抗癌协会乳腺癌专业委员会.中国抗癌协会乳腺癌诊治指南与规范(2015版)[J].中国癌症杂志,2015,25(9):692-754.Professional Committee on Breast Cancer,China Anti-Cancer Association.Guidelines and specifications for diagnosis and treatment of breast cancer of China Anti-Cancer Association(2015Edition)[J].China Oncology,2015,25(9):692-754.
[7]薛会丽,林丹玫,陈雪美,等.1891例男性不育患者的细胞遗传学分析[J].中华医学遗传学杂志,2017,34(5):772-774.DOI:10.3760/cma.j.issn.1003-9406.2017.05.033.Xue HL,Lin DM,Chen XM,et al.Cytogenetic analysis of 1891male infertility patients[J].Chinese Journal of Medical Genetics,2017,34(5):772-774.DOI:10.3760/cma.j.issn.1003-9406.2017.05.033.
[8]Chen X,Williams-Burris SM,Mc Clusky R,et al.The Sex Chromosome Trisomy mouse model of XXY and XYY:metabolism and motor perform ance[J].Biol Sex Differ,2013,4(1):15.DOI:10.1186/2042-6410-4-15.
[9]Overvad S,Bay K,Bojesen A,et al.Low INSL3 in Klinefelter syndrome is related to osteocalcin,testosterone treatment and body composition,as well as measures of the hypothalamic-pituitarygonadal axis[J].Andrology,2014,2(3):421-427.DOI:10.1111/j.2047-2927.2014.00204.x.
[10]Ozveri H,Kayabasoglu F,Demirel C,et al.Outcomes of microdissection TESE in patients with non-mosaic Klinefelter's syndrome without hormonal treatment[J].Int J Fertil Steril,2015,8(4):421-428.
[11]季兴哲,周梁,孙建华,等.应用ROC曲线评价血清FSH、LH及T在非嵌合型克氏综合征诊断中的价值[J].中国优生与遗传杂志,2017,25(11):64-66.DOI:10.13404/j.cnki.cjbhh.2017.11.020.Ji XZ,Zhou L,Sun JH,et al.Evaluation of serum FSH,LH and T in the diagnosis of non-chimeric Kirschner syndrome by ROCcurve[J].Chinese Journal of Birth Health&Heredity,2017,25(11):64-66.DOI:10.13404/j.cnki.cjbhh.2017.11.020.
[12]Busch AS,Tüttelmann F,Zitzmann M,et al.The FSHB-211G>Tvariant attenuates serum FSH levels in the supraphysiological gonadotropin setting of Klinefelter syndrome[J].Eur J Hum Genet,2015,23(5):700-703.DOI:10.1038/ejhg.2014.142.
[13]Cabrol S,Ross JL,Fennoy I,et al.Assessment of Leydig and Sertoli cell functions in infants with nonmosaic Klinefelter syndrome:insulin-like peptide 3 levels are normal and positively correlated with LH levels[J].J Clin Endocrinol Metab,2011,96(4):E746-753.DOI:10.1210/jc.2010-2103.
[14]Fentiman IS.The biology of male breast cancer[J].Breast,2018,38:132-135.DOI:10.1016/j.breast.2018.01.001.
[15]Kerdivel G,Boudot A,Habauzit D,et al.Activation of the MKL1/actin signaling pathway induces hormonal escape in estrogen-responsivebreast cancer cell lines[J].Mol Cell Endocrinol,2014,390(1-2):34-44.DOI:10.1016/j.mce.2014.03.009.
[16]Inci M,Akgul O,Baydilli N,et al.Increased femoral cartilage thickness in patients with Klinefelter syndrome[J].Am J Mens Health,2013,7(1):54-57.DOI:10.1177/1557988312458449.