抗米勒管激素用于年轻乳腺癌患者卵巢功能抑制个体化治疗的评价

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。     

中国早期乳腺癌卵巢功能抑制临床应用专家共识（2024年版）

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...     

基于超高效串联质谱的氨基酸代谢组学预测晚期乳腺癌化疗反应初探

  目的  探讨晚期乳腺癌患者化疗前(基线)和化疗第1个疗程后(预后)血清中32种氨基酸的变化,预测其指导晚期乳腺癌化疗敏感性的价值。  方法  选取2015年3月至2016年10月于辽宁省肿瘤医院行化疗的女性晚期乳腺癌患者73例,分别在化疗前和化疗第1个疗程后采集外周血2 mL,经超高效串联质谱(LC-MS/MS)检测血清中32种氨基酸的含量水平。采用影像学检查对化疗2~4个疗程后患者行预后评估,分为好转组和恶化组,并分析氨基酸含量水平的变化。  结果  32种氨基酸含量水平为3~180 000 pmol/L。与基线相比,好转组的甘氨酸和L-谷氨酰胺相对含量显著上升,而恶化组显著下降;好转组的肌氨酸显著下降,而恶化组变化不明显;好转组和恶化组的L-苏氨酸、牛磺酸、亚氨基二乙酸和L-谷氨酸均显著上升。  结论  甘氨酸和肌氨酸等氨基酸在行化疗前和化疗第1个疗程后的变化对晚期乳腺癌化疗疗效具有一定的预测价值,较影像学检查可能更早预测化疗疗效,有助于指导患者的治疗。关键词晚期乳腺癌氨基酸代谢化疗敏感性超高效串联质谱      

中国早期乳腺癌卵巢功能抑制临床应用专家共识（2021年版）

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。     

HER-2/CEP17信号比与乳腺癌新辅助化疗后病理完全缓解的相关性研究

  目的  评价HER-2/CEP17信号比与乳腺癌新辅助化疗后病理完全缓解的相关性及其预测作用。  方法  收集中山大学孙逸仙纪念医院2013年1月至2017年12月635例临床分期为ⅡB~Ⅲ期浸润性乳腺癌行新辅助化疗患者的临床资料。根据患者新辅助化疗后手术病理标本,分为病理完全缓解组117例和非病理完全缓解组518例。统计分析HER-2/CEP17信号比是否为全体患者以及联合和非联合靶向治疗亚组病理完全缓解的独立预测因子,并且分析HER-2/CEP17信号比是否与病理完全缓解率具有相关性。  结果  635例乳腺癌患者中,总体病理完全缓解率为18.4%（117/635）,多因素Logistic回归分析结果显示T分期（OR为0.500,95%CI为0.350~0.712,P < 0.001）、Ki-67表达（OR为3.461,95%CI为1.891~6.333,P < 0.001）、分子分型（OR为1.458,95% CI为1.188~1.791,P < 0.001）、HER-2基因拷贝数（OR为6.173,95%CI为2.110~17.857,P=0.001）及HER-2/CEP17信号比（OR为9.076,95%CI为3.142~26.215,P < 0.001）为乳腺癌新辅助化疗获得病理完全缓解的独立预测因子。分析显示HER-2/CEP17信号比也是新辅助化疗联合靶向治疗和非联合靶向治疗亚组的独立预测因子。Spearman秩相关性分析显示HER-2/CEP17信号比与乳腺癌新辅助化疗病理完全缓解率具有相关性（r=0.235,P < 0.001）。  结论  HER-2/CEP17信号比与乳腺癌新辅助化疗后病理完全缓解具有相关性,是其独立预测因子。      

化疗对围绝经期乳腺癌患者性激素水平的影响

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。     

乳腺癌患者IDO表达及活性与新辅助化疗疗效的相关性研究

  目的  分析吲哚胺2,3-双加氧酶（indoleamine 2,3-dioxygenase,IDO）在乳腺癌患者癌组织中表达及其在外周血中活性与新辅助化疗疗效的关系。  方法  收集2015年9月至2016年12月天津医科大学肿瘤医院53例行新辅助化疗乳腺癌患者的肿瘤穿刺标本和血液标本,采用免疫组织化学法及高效液相色谱法检测癌组织中IDO表达及外周血中色氨酸（tryptophan,Trp）、犬尿氨酸（kynurenine,Kyn）浓度与IDO活性,分析IDO表达及活性与化疗疗效的相关性。  结果  新辅助化疗前乳腺癌组织中IDO表达与临床T分期（P=0.006）、N分期（P=0.020）、临床分期（P=0.045）及ER状态（P=0.014）有关。新辅助化疗前外周血中IDO高活性伴随癌组织中IDO高表达（P=0.004）,并与临床T分期（P=0.019）及N分期（P=0.047）有关。单因素分析显示新辅助化疗临床疗效与化疗前临床T分期（P=0.049）、ER状态（P=0.025）及分子分型（P=0.014）有关;病理完全缓解（pathologic complete response,pCR）与化疗前临床T分期（P=0.014）有关。更重要的是新辅助化疗临床疗效及pCR均与化疗前IDO表达及活性有关（均P < 0.05）。多因素分析显示新辅助化疗前外周血中IDO活性是影响pCR的唯一独立因素（P=0.032）。  结论  新辅助化疗前乳腺癌组织中IDO表达和外周血中IDO活性与化疗疗效相关,可以为临床预测化疗是否敏感提供一定信息。      

用ROC曲线评价雌激素、卵泡刺激素、黄体生成素判断乳腺癌患者绝经状态

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。     

术后化疗对早期肺大细胞神经内分泌肿瘤患者生存期的影响

  目的  探讨术后化疗对早期肺大细胞神经内分泌肿瘤（large cell neuroendocrine carcinoma,LCNEC）患者生存期的影响。  方法  回顾性分析2008年1月至2014年12月在上海交通大学附属胸科医院50例行肺癌根治性切除及系统性淋巴结清扫LCNEC患者的临床资料,根据术后是否接受化疗将50例患者分为化疗组（n=32）和非化疗组（n=18）。随访其生存状况。  结果  化疗组和非化疗组中位生存时间分别为48个月和29个月,5年总生存率分别为72.5%和35.6%。单因素及多因素Cox分析均表明:术后辅助化疗为LCNEC患者OS的预后影响因素（P=0.005;HR=0.281,P=0.008）。  结论  术后化疗可提高早期LCNEC术后患者的远期生存率。      

乳腺癌新辅助化疗中循环肿瘤细胞的动态变化及疗效观察

  目的  通过检测新辅助化疗乳腺癌患者化疗前及化疗后各周期外周血中循环肿瘤细胞的变化,比较TC及TEC两种不同新辅助化疗方案的疗效。  方法  选取2010年1月~2012年12月间本院收治的96例局部晚期乳腺癌患者,随机分为两组,分别给予TC（多西他赛+环磷酰胺）和TEC（多西他赛+表柔比星+环磷酰胺）两种方案4个周期。分别抽取新辅助化疗前、新辅助化疗1、2、3、4个疗程后48h患者外周血5 mL,并采用流式细胞术测量外周血中循环肿瘤细胞含量,比较两种新辅助化疗方案疗效。  结果  两组患者新辅助化疗前年龄、绝经状态、ER、PR、C-erbB-2、肿物大小、临床分期等一般资料无统计学差异;两组患者新辅助化疗前外周血中循环肿瘤细胞值无明显差异;新辅助化疗前,两组患者外周血中循环肿瘤细胞含量与肿物体积有关系,肿物>5 cm者循环肿瘤细胞含量明显高于肿物≤5 cm者（P均 < 0.05）;两种新辅助化疗方案化疗后,两组患者外周血中循环肿瘤细胞值随化疗周期进行而持续降低（P均 < 0.05）,同时,使用TEC方案患者外周血中循环肿瘤细胞值明显低于使用TC方案患者（P均 < 0.05）。  结论  使用TC和TEC方案新辅助化疗可使局部晚期乳腺癌患者病灶缩小,外周血中循环肿瘤细胞值降低。同时,监测外周血中循环肿瘤细胞值变化,可评价新辅助化疗方案疗效。      

A pilot study of predictive markers of chemotherapy-related amenorrhea among premenopausal women with early stage breast cancer

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.     

Choosing relevant endpoints for older breast cancer patients in clinical trials: an overview of all current clinical trials on breast cancer treatment

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.     

The utility of anti-Müllerian hormone in the diagnosis and prediction of loss of ovarian function following chemotherapy for early breast cancer

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.     

Prediction of Postchemotherapy Ovarian Function Using Markers of Ovarian Reserve

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.     

Predicting Ovarian Activity in Women Affected by Early Breast Cancer: A Meta‐Analysis‐Based Nomogram

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.     

双侧原发性乳腺癌两癌间隔时间对ER PR HER-2表达一致性及预后的影响

  目的  分析两癌发生间隔时间对双侧原发性乳腺癌雌激素受体(ER)、孕激素受体(PR)及人表皮生长因子受体2(HER-2)表达一致性及预后的影响。  方法  回顾性分析366例双侧原发性乳腺癌(bilateral primarv breast cancer, BPBC)患者的病理资料, 按照两癌发生的间隔时间进行分组, 侧重分析不同组内第一原发癌与第二原发癌ER、PR、HER-2表达的一致性及两癌间隔时间对BPBC预后的影响。  结果  BPBC第一原发癌与第二原发癌的ER、PR、HER-2表达呈正相关, 两癌间隔时间≤12个月的BPBC双侧ER、PR、HER-2表达密切相关(P < 0.05), 而两癌间隔时间 > 12个月的BPBC双侧ER、PR、HER-2表达相关性无统计学意义(P > 0.05)两癌间隔时间≤12个月较 > 12个月发生者远期生存率低, 预后差。  结论  12个月内发生的BPBC两癌在ER、PR、HER-2表达方面具有较高的相似性, 远期生存率较低, 同异时性BPBC以12个月划分更能反映两癌之间的联系及预后。      

肿瘤浸润淋巴细胞比例对乳腺癌新辅助化疗疗效的预测作用

  目的   评价乳腺癌患者行新辅助化疗前穿刺标本中的肿瘤浸润淋巴细胞(tumor infiltrating lymphocytes,TIL)比例与术后病理评估疗效之间的关系。  方法  收集2015年11月至2017年4月156例于天津医科大学肿瘤医院行乳腺肿物穿刺后病理证实为浸润性乳腺癌,并行新辅助化疗及手术的女性患者的临床资料。计算穿刺标本中TIL比例,并分为高、中、低组,利用组织病理学评价标准评估新辅助化疗疗效并分析两者的相关性。  结果  新辅助化疗总有效率为78.2%(122/156),高TIL比例组的新辅助化疗有效率高于低TIL比例组(P < 0.01),激素受体阴性乳腺癌的TIL比例明显高于激素受体阳性乳腺癌(P < 0.01)。新辅助化疗疗效仅与TIL比例相关,与激素受体状态、HER-2受体状态、Ki-67阳性细胞比例无相关性。  结论   乳腺癌穿刺标本中的TIL比例是预测乳腺癌新辅助化疗疗效的独立因子,TIL比例较高的乳腺癌患者的新辅助化疗疗效常更佳。      

无糖尿病病史的乳腺癌患者系统治疗后糖耐量异常状况研究

  目的  通过口服葡萄糖耐量试验(OGTT)了解无糖尿病病史的乳腺癌患者系统治疗后糖耐量异常状况。  方法  对121例系统治疗(手术治疗和/或化疗)结束后3个月以上无糖尿病病史的乳腺癌患者行OGTT检测, 检测空腹及OGTT餐后2 h血糖值以明确此类患者有无伴随糖耐量异常, 同期6例有糖尿病病史的乳腺癌患者未行OGTT检测。  结果  患者平均随访年龄为50.4岁, 系统治疗后平均随访时间为19个月。在121例无糖尿病病史的乳腺癌患者中:糖尿病(即未知晓糖尿病)和糖尿病前期发生率分别为19.8%(24/121)和45.5%(55/121), 糖耐量相对正常仅占34.7%(42/121);在所有127例系统治疗后的乳腺癌患者中已知晓糖尿病、未知晓糖尿病及糖尿病前期发生率分别为4.72%(6/127)、18.9%(24/127)和43.3%(55/127), 其中糖尿病的未知晓率高达80%。约80%的糖尿病及74.5%糖尿病前期的诊断需经OGTT餐后2 h血糖检测确诊而非空腹血糖检测。  结论  系统治疗后的乳腺癌患者存在明显的糖代谢紊乱, 伴有高比例的未知晓糖尿病和糖尿病前期, 对此类患者建议行OGTT检测, 以利于早期诊断和防治糖尿病的发生, 改善预后。      

乳腺癌中GFRA1表达临床意义的生物信息学分析

  目的  通过生物信息学的方法分析胶质细胞系源性神经营养因子受体1（glial cell line derived neurotrophic factor α1,GFRA1）在乳腺癌组织中表达情况及其临床意义。  方法  全面检索GEO、TCGA、Oncomine、Kmplot数据库分析GFRA1在乳腺癌中表达情况,分析其预测化疗、内分泌治疗疗效和预后的价值。  结果  GFRA1在不同类型乳腺癌组织中高表达（P < 0.05）,与ER（r= 0.66）、PR（r=0.22）表达水平呈正相关,与HER-2（r=-0.09）、Ki-67（r=-0.12）表达水平呈负相关。GFRA1低表达乳腺癌患者对他莫昔芬和多柔比星易产生耐药。GFRA1表达水平与乳腺癌患者预后显著相关（P < 0.05）,GFRA1高表达患者总生存率、无复发生存率高于低表达患者。  结论  GFRA1在乳腺癌组织中高表达,低表达乳腺癌患者对他莫昔芬和多柔比星耐药,且预后较差。