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背景与目的:年轻乳腺癌患者应用促黄体生成素释放激素类似物戈舍瑞林治疗没有个体化用药方案,并缺乏临床可用的指导依据。该研究皆在探讨抗米勒管激素(anti-Müllerian hormone,AMH)在年轻乳腺癌患者卵巢功能抑制个体化治疗的评价作用。方法:选取2012年5月—2014年1月在上海交通大学附属仁济医院因雌激素受体(estrogen receptor,ER)和孕激素受体(progesterone receptor,PR)阳性的乳腺癌41例患者,术前随机分为戈舍瑞林6个疗程+化疗组(简称戈舍瑞林组)20例,化疗组21例,30例同年龄组健康妇女为正常对照组,随访(17.4±6.2)个月。观察两组治疗后的停经时间与复潮时间,于术前1个月、戈舍瑞林组或化疗组术后月经复潮后3、6个月检测AMH、促卵泡激素(follicle-stimulating hormone,FSH)和E2水平。正常对照组在相应时间段内检测AMH、FSH和E2水平。结果:3组患者的术前临床资料及术前FSH、E2水平差异均无统计学意义(P>0.05),乳腺癌患者术前AMH水平较正常对照组降低,差异有统计学意义(P=0.04);戈舍瑞林组较化疗组停经时间更短,差异有统计学意义(P=0.00);戈舍瑞林组较化疗组复潮时间更短,差异有统计学意义(P=0.00);与正常对照组及术前比较,戈舍瑞林组及化疗组FSH、E2水平在5个测定时间的差异均无统计学意义(P>0.05);戈舍瑞林组及化疗组在5个测定时间的AMH水平均显著降低,差异均有统计学意义(P=0.00),两组在复潮后3、6个月AMH水平逐渐上升,差异均有统计学意义(P<0.05);与化疗组相比,戈舍瑞林组的AMH水平下降明显,戈舍瑞林组的AMH水平在复潮6个月后比化疗组升高,差异均有统计学意义(P<0.05)。结论:年轻乳腺患者在卵巢功能抑制治疗+化疗过程中,AMH较其他评价卵巢储备的指标明显下降,在其他指标恢复术前水平后仍提示卵巢受损,提示AMH可以作为评价年轻乳腺癌患者卵巢功能的指标,亦有可能成为戈舍瑞林个体化治疗的评价指标。 相似文献
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中国抗癌协会乳腺癌专业委员会 《中国癌症杂志》2024,(3):316-334
中国乳腺癌患者发病年龄较轻,60%的女性患者在诊断时为绝经前。与绝经后相比,未绝经女性卵巢功能旺盛,可持续大量分泌雌激素、促进乳腺癌细胞增殖。卵巢功能抑制(ovarian function suppression,OFS)已用于乳腺癌临床治疗数十年,大量循证证据表明,单用OFS和加用OFS均可降低未绝经女性乳腺癌的复发风险并改善生存。部分OFS研究的长期随访数据(SOFT/TEXT研究12和13年随访、STO-5研究20年随访、亚裔人群的ASTRRA研究8年随访)近期陆续公布,进一步证实对于早期乳腺癌患者加用OFS可显著降低10年以上的复发风险,提高治愈可能。monarchE和NATALEE研究显示,部分CDK4/6抑制剂叠加在绝经前早期乳腺癌患者含有药物去势[促性腺激素释放激素类似物(gonadotropin releasing hormone analog,GnRHa)]的辅助内分泌治疗方案时仍可进一步增加生存获益。中国抗癌协会乳腺癌专业委员会召集了国内乳腺癌治疗领域的临床专家,在2021年版的基础上共同商讨编制了《中国早期乳腺癌卵巢功能抑制临床应用专家共识(2024年版)》。本共... 相似文献
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卵巢功能抑制(ovarian function suppression,OFS)已经应用于乳腺癌治疗数十年,早期辅助治疗研究证实,单独进行OFS能够降低50岁以下乳腺癌患者的复发风险,改善生存情况。鉴于新的循证医学数据不断累积,中国抗癌协会乳腺癌专业委员会遂召集国内乳腺癌专家,在《中国早期乳腺癌卵巢功能抑制临床应用专家共识(2018年版)》的基础上共同商讨制订了《中国早期乳腺癌卵巢功能抑制临床应用专家共识(2021年版) 》。2021年版共识建议,将药物去势[促性腺激素释放激素激动剂(gonadotropin releasing hormone agonist,GnRHa)]作为绝经前激素受体阳性的早期乳腺癌OFS的首选。中高危绝经前激素受体阳性乳腺癌患者推荐接受OFS的内分泌治疗;低危患者推荐选择性雌激素受体调节剂(selective estrogen receptor modulators,SERM)单药治疗;使用芳香化酶抑制剂(aromatase inhibitor,AI)代替SERM治疗的绝经前患者,需要同时接受OFS治疗。关于OFS联合方案,对绝经前激素受体阳性早期乳腺癌的中危和高危患者,或亚群处理效果模式图(subpopulation treatment effect pattern plot,STEPP)分析的较高风险患者推荐OFS联合AI治疗,OFS联合SERM治疗也是合理的选择。对存在SERM禁忌证的任何风险级别患者,推荐OFS联合AI治疗。关于OFS的使用时机,建议根据激素受体阳性乳腺癌患者化疗前的卵巢功能状态,决定辅助内分泌治疗方案。如果考虑卵巢保护,推荐GnRHa同步化疗,不影响患者的生存获益;如果不考虑卵巢保护,推荐GnRHa可以在化疗结束后直接序贯使用。已接受化疗的患者不推荐确认卵巢功能状态后再使用GnRHa。GnRHa辅助内分泌治疗的标准疗程应为5年。完成5年联合OFS的内分泌治疗后,如未绝经且耐受性良好,推荐继续5年联合OFS的内分泌治疗或5年SERM治疗。低危选择OFS替代化疗的患者,可考虑OFS联合内分泌治疗时长为2年。推荐与患者充分沟通可能出现的不良事件,选用合适的药物去势治疗方案。合理的安全管理能够有效地缓解不良反应,增加患者治疗的依从性。对于接受药物去势的患者,不常规推荐在药物去势治疗过程中监测雌激素水平并根据检测报告来决定是否继续药物去势。但在药物去势后,怀疑不完全的卵巢功能抑制时[包括改变用法如注射人员缺乏相关经验、更换剂型或出现某些可能提示卵巢功能恢复的生理变化如月经恢复和(或)更年期症状的周期性波动时],可以进行雌激素水平检测。绝经前乳腺癌患者,无论激素受体阳性或阴性,推荐在(新)辅助化疗前和化疗过程中使用OFS药物保护卵巢功能,降低卵巢功能早衰的发生风险,减少生育能力损害。推荐化疗前2周开始使用GnRHa,每28 d 1次,直至化疗结束后2周给予最后一剂药物。此外共识还建议,激素受体阳性乳腺癌患者抗肿瘤药物的临床试验,应尽可能纳入绝经前女性,在雌激素充分抑制的前提下,探索抗肿瘤药物对肿瘤生物学特性和患者长期生活质量的影响。 相似文献
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背景与目的:目前围绝经期乳腺癌化疗后的闭经与绝经容易混淆。本研究探讨围绝经期乳腺癌患者术后辅助化疗对性激素水平的影响,为乳腺癌辅助内分泌治疗药物的选择提供依据。方法:将100例围绝经期乳腺癌患者分为45~50岁组(n=44)及51~55岁组(n=56),术后均行辅助化疗6个疗程。分别于化疗前、化疗结束时、化疗结束后3个月及6个月检测卵泡刺激激素(follicle-stimulating hormone,FSH)及雌二醇(estradiol,E2)的水平,分析围绝经期乳腺癌患者性激素水平的变化。结果:经6个疗程辅助化疗后,45~50岁组患者中,6个月后血清FSH及E2仅有2.3%处于绝经期水平,而51~55岁组血清FSH及E2有76.78%处于绝经期水平,差异有统计学意义(P<0.05)。结论:围绝经期乳腺癌患者化疗后停经持续1年以上,且血清FSH及E2处于绝经期水平,尤其50岁以上可考虑为已绝经。 相似文献
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目的应用ROC曲线评价雌二醇(estradiol,E2)、卵泡刺激素(follicle stimulating hormone,FSH)和黄体生成素(luteinizing hormone,LH)3项性激素对浸润性乳腺癌患者绝经状态的判断能力。方法分析本院128例绝经前及204例已绝经浸润性乳腺癌患者的性激素检测结果。应用ROC曲线评价单项性激素及它们联合的判断能力和判断点(Cut-offPoint)。结果单项E2、FSH和LH的ROC曲线下面积分别为0.9395(95%CI:0.9110~0.9679)、0.9714(95%CI:0.9514~0.9914)和0.9053(95%CI:0.8681~0.9424);Youden指数最大时的判断点分别为49.52pg/ml、21.96mU/ml和13.25mU/ml。FSH的ROC曲线下面积分别和E2(P=0.036)、LH相比(P〈0.001),差别均具有统计学意义。经计算E2和FSH进入联合判断模型,联合判断的曲线下面积为0.9774(95%CI:0.9597~0.9952),Youden指数最大时的判断点的绝经概率(P绝经)=0.46。结论单项E2、FSH和LH均可判断乳腺癌患者的绝经状态,其中FSH的能力好于E2和LH。而E2和FSH的联合判断好于单项指标。由于LH的ROC曲线下面积最小,经计算没能进入联合判断模型,故不推荐用其判断乳腺癌患者的绝经状态。可根据临床需要,调整ROC曲线的绝经概率,选择判断点,并了解在该判断点下的误诊率或漏诊率的大小。 相似文献
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Anders C Marcom PK Peterson B Gu L Unruhe S Welch R Lyons P Behera M Copland S Kimmick G Shaw H Snyder S Antenos M Woodruff T Blackwell K 《Cancer investigation》2008,26(3):286-295
Background: Premenopausal women treated for early stage breast cancer (ESBC) are at risk for chemotherapy-related amenorrhea (CRA). Prospectively-validated, predictive markers of CRA are needed. Patients and Methods: Premenopausal women with ESBC and planned chemotherapy (>/= 25% risk of amenorrhea) were evaluated. Follicle stimulating hormone (FSH), estradiol, Inhibin A and B, anti-Müllerian hormone (AMH), and quality of life (QOL) were prospectively evaluated pre-, post-, 6 months and 1 year post-chemotherapy and correlated with age and menstrual status. CRA was defined as absence of menses 1 year post-chemotherapy. Results: Forty-four women were evaluated at the time of analysis. Median age at diagnosis and FSH 1 year post-chemotherapy were higher among women with CRA (44 yrs [33-51] vs. 40 yrs [31-43]; p = 0.03; 39.8 vs. 5.0 mLU/mL, p = 0.0058, respectively). Median estradiol 1 year post-chemotherapy was higher among women who resumed menses (108.3 vs. 41.3 pg/mL, p = 0.01). Pre-chemotherapy median Inhibin B and AMH were lower among women with CRA (33.2 vs. 108.8 pg/mL; p = 0.03; 0.16 vs. 1.09 ng/mL, p = 0.02, respectively). The risk of CRA was increased among women with lower pre-chemotherapy Inhibin B (RR = 1.67, p = 0.15) and AMH (RR = 1.83, p = 0.05). Amongst women whose pre-chemotherapy Inhibin B and AMH values were below the median, the incidence of CRA was 87.5%. Conclusions: Results indicate that pre-chemotherapy Inhibin B and AMH are lower among women experiencing CRA and may be predictive of CRA among premenopausal women facing chemotherapy for ESBC. 相似文献
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N. A. de Glas M. E. Hamaker M. Kiderlen A. J. M. de Craen S. P. Mooijaart C. J. H. van de Velde B. C. van Munster J. E. A. Portielje G. J. Liefers E. Bastiaannet 《Breast cancer research and treatment》2014,144(3):591-597
This study aimed to investigate whether pre-chemotherapy anti-mullerian hormone (AMH) is a biomarker for chemotherapy-related amenorrhea (CRA) in breast cancer patients. A multicenter randomized controlled trial, ECOG5103, assigned patients with early stage breast cancer to standard doxorubicin-cyclophosphamide followed by paclitaxel with either placebo or one of two durations of bevacizumab therapy. Five hundred ninety-one patients were part of the decision-making/quality of life substudy, in which there were surveys from baseline through 18-month follow-up. One hundred twenty-four women were included in this analysis of menses data because they were premenopausal at enrollment, responded to the 12-month survey, had not undergone bilateral oophorectomy or ovarian function suppression before that survey, and had serum banked for research before chemotherapy. One hundred of the 124 also responded to the 18-month survey. Median age was 45 years (range 25–55), and median serum AMH level was 0.11 ng/mL (range 0.01–8.63) prior to treatment. Eighty-two percent had CRA at 12 months, and 81 % at 18 months. In multivariate analyses, older age (p = 0.0003) was the only statistically significant predictor of 12-month CRA, but at 18-months, lower pre-chemotherapy AMH (p = 0.04) and older age (p = 0.008) were both statistically significant predictors of CRA. Race, bevacizumab therapy, and tamoxifen use were not statistically significantly associated with CRA after adjustment for AMH and age. Pre-chemotherapy AMH level is a potential novel biomarker for CRA in premenopausal women with early stage breast cancer. Further research to evaluate the clinical utility of AMH testing is warranted. 相似文献
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AimChemotherapy results in permanent loss of ovarian function in some premenopausal women. Accurate identification in women with hormone-sensitive early breast cancer (eBC) would allow optimisation of subsequent endocrine treatment. We sought to assess whether analysis of anti-Müllerian hormone (AMH) using a sensitive automated assay could identify women who would not regain ovarian function after chemotherapy.MethodsData from women in the Ovarian Protection Trial in Premenopausal Breast Cancer Patients (OPTION) trial of goserelin (a gonadotrophin-releasing hormone (GnRH) analogue) for ovarian protection were analysed. Women were assessed for premature ovarian insufficiency (POI: amenorrhoea with elevated follicle-stimulating hormone (FSH)) at 24 months after diagnosis. The accuracy of AMH for the diagnosis of POI and its prediction from measurement at the end of chemotherapy was calculated.ResultsAMH below the level of detection showed good diagnostic accuracy for POI at 24 months (n = 73) with receiver operating characteristic (ROC) area under the curve of 0.86, sensitivity 1.0 and specificity 0.73 at the assay limit of detection. In women aged >40 at diagnosis who did not receive goserelin, AMH measured at end of chemotherapy also gave good prediction of POI at 24 months (area under the curve (AUC) 0.89 95% CI 0.75–1.0, n = 32), with sensitivity 0.91, specificity 0.82, diagnostic odds ratio (DOR) 42.8. FSH gave slightly lower AUC, and specificity was low at 0.55. Age but not tamoxifen impacted on AMH levels.ConclusionUsing this sensitive AMH assay, the finding of an undetectable AMH level in women aged >40 at the end of chemotherapy for eBC gave a good prediction that ovarian function would not return. This may allow alterations in post-chemotherapy endocrine management. 相似文献
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N. Lynn Henry Rong Xia Anne F. Schott Daniel McConnell Mousumi Banerjee Daniel F. Hayes 《The oncologist》2014,19(1):68-74
Background.
Reproductive-aged women frequently receive both chemotherapy and endocrine therapy as part of their treatment regimen for early stage hormone receptor-positive breast cancer. Chemotherapy results in transient or permanent ovarian failure in the majority of women. The difficulty in determining which patients will recover ovarian function has implications for adjuvant endocrine therapy decision making. We hypothesized that pretreatment serum anti-Müllerian hormone (AMH) and inhibin B concentrations would predict for ovarian function following chemotherapy.Methods.
Pre- and perimenopausal women aged 25–50 years with newly diagnosed breast cancer were enrolled. Subjects underwent phlebotomy for assessment of serum AMH, inhibin B, follicle-stimulating hormone, and estradiol prior to chemotherapy and 1 month and 1 year following completion of treatment. Associations among hormone concentrations, clinical factors, and biochemically assessed ovarian function were assessed.Results.
Twenty-seven subjects were evaluable for the primary endpoint. Median age was 41. Twenty subjects (74.1%) experienced recovery of ovarian function within 18 months. Of the 26 evaluable subjects assessed prior to chemotherapy, 19 (73.1%) had detectable serum concentrations of AMH. The positive predictive value of a detectable baseline serum AMH concentration for recovery of ovarian function was 94.7%, and the negative predictive value was 85.7%. On univariate analysis, younger age and detectable serum AMH concentration at chemotherapy initiation were predictive of increased likelihood of recovery of ovarian function.Conclusion.
Prechemotherapy assessment of serum AMH may be useful for predicting postchemotherapy ovarian function. This finding has implications for decision making about adjuvant endocrine therapy in premenopausal women treated with chemotherapy. 相似文献15.
Predicting Ovarian Activity in Women Affected by Early Breast Cancer: A Meta‐Analysis‐Based Nomogram
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Paolo Marchetti Valentina Sini Liana De Vecchis Salvatore Maria Corsello Francesco Torino 《The oncologist》2015,20(10):1111-1118
Background.
The assessment of ovarian reserve in premenopausal women requiring anticancer gonadotoxic therapy can help clinicians address some challenging issues, including the probability of future pregnancies after the end of treatment. Anti-Müllerian hormone (AMH) and age can reliably estimate ovarian reserve. A limited number of studies have evaluated AMH and age as predictors of residual ovarian reserve following cytotoxic chemotherapy in breast cancer patients.Materials and Methods.
To conduct a meta-analysis of published data on this topic, we searched the medical literature using the key MeSH terms “amenorrhea/chemically induced,” “ovarian reserve,” “anti-Mullerian hormone/blood,” and “breast neoplasms/drug therapy.” Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements guided the search strategy. U.K. National Health Service guidelines were used in abstracting data and assessing data quality and validity. Area under the receiver operating characteristic curve (ROC/AUC) analysis was used to evaluate the predictive utility of baseline AMH and age model.Results.
The meta-analysis of data pooled from the selected studies showed that both age and serum AMH are reliable predictors of post-treatment ovarian activity in breast cancer patients. Importantly, ROC/AUC analysis indicated AMH was a more reliable predictor of post-treatment ovarian activity in patients aged younger than 40 years (0.753; 95% confidence interval [CI]: 0.602–0.904) compared with those older than 40 years (0.678; 95% CI: 0.491–0.866). We generated a nomogram describing the correlations among age, pretreatment AMH serum levels, and ovarian activity at 1 year from the end of chemotherapy.Conclusion.
After the ongoing validation process, the proposed nomogram may help clinicians discern premenopausal women requiring cytotoxic chemotherapy who should be considered high priority for fertility preservation counseling and procedures.Implications for Practice:
In general, a nomogram helps clinicians better visualize a specific risk for a single patient. In premenopausal women affected by early breast cancer who need adjuvant cytotoxic regimens, the proposed nomogram—based on the assessment of pretreatment age and anti-Müllerian hormone serum levels—can assess the personal probability of maintaining ovarian activity at 1 year from the end of chemotherapy. The ongoing validation process is also evaluating other key factors contributing to post-treatment ovarian activity (i.e., type of cytotoxic regimen) and will confirm the nomogram’s reliability and clinical utility. 相似文献16.
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