Estrogen metabolism in menopausal hormone users in the women's health initiative observational study: Does it differ between estrogen plus progestin and estrogen alone?

The WHI found an unexpected reduced breast cancer risk in women using CEE alone. We hypothesized CEE alone induces estrogen hydroxylation along the 2-pathway rather than the competing 16-pathway, a pattern linked to reduced postmenopausal breast cancer risk. One thousand eight hundred and sixty-four women in a WHIOS case–control study of estrogen metabolism and ovarian and endometrial cancer were studied of whom 609 were current E + P users (351 used CEE + MPA), while 272 used E alone (162 used CEE). Fifteen EM were measured, and analyses were conducted for each metabolite, hydroxylation pathway (2-, 4-, or 16-pathway) and ratios of pathway concentrations using inverse probability weighted linear regression. Compared to E + P users, all EM were higher in E alone users (significant for unconjugated estrone, total/conjugated estradiol, total/unconjugated 2-methoxyestrone, 4-methoxyestrone and unconjugated estriol). The relative concentrations of 2- and 4-pathway EM did not differ between the MHT users (2-pathway EM comprised 15% and 4-pathway EM <2% of the total), but 16-pathway EM were lower in E alone users (p = 0.036). Ratios of 2- and 4-pathway EM compared to 16-pathway EM were significantly higher in E alone compared to E + P users. Similar but not significant patterns were observed in CEE-alone and CEE + MPA users. Our data suggest that compared to E + P users, women using E alone have more extensive metabolism via the 2- vs. the competing 16-pathway. This is consistent with epidemiologic evidence of reduced postmenopausal breast cancer risk associated with this metabolic profile and may provide a clue to the breast cancer risk reduction in CEE alone users during the WHI.     

Predictors of Survival after Yttrium-90 Radioembolization of Chemotherapy-Refractory Hepatic Metastases from Breast Cancer

PurposeTo determine predictors of survival after transarterial radioembolization of hepatic metastases from breast cancer.Materials and MethodsTwenty-four patients with chemotherapy-refractory hepatic metastases from breast cancer who underwent radioembolization from 2013 to 2018 were evaluated based on various demographic and clinical factors before and after treatment. Overall survival (OS) was estimated by Kaplan–Meier method. Log-rank analysis was performed to determine predictors of prolonged OS from the time of first radioembolization and first hepatic metastasis diagnosis.ResultsMedian OS times were 35.4 and 48.6 months from first radioembolization and time of hepatic metastasis diagnosis, respectively. Radioembolization within 6 months of hepatic metastasis diagnosis was a positive predictor of survival from first radioembolization, with median OS of 38.9 months vs 22.1 months for others (P = .033). Estrogen receptor (ER)–positive status predicted prolonged survival (38.6 months for ER⁺ vs 5.4 months for ER⁻; P = .005). The presence of abdominal pain predicted poor median OS: 12.8 months vs 38.6 months for others (P < .001). The presence of ascites was also a negative predictor of OS (1.7 months vs 35.4 months for others; P = .037), as was treatment-related grade ≥ 2 toxicity at 3 months (5.4 months vs 38.6 months for others; P = .017).ConclusionsIn patients with metastatic breast cancer, radioembolization within 6 months of hepatic metastasis diagnosis and ER⁺ status appear to be positive predictors of prolonged survival. Conversely, baseline abdominal pain, baseline ascites, and treatment-related grade ≥ 2 toxicity at 3 months after treatment appear to be negative predictors of OS.     

浅谈“七损八益”与三阴性乳腺癌雌激素受体、雄激素受体的表达

乳腺癌是我国女性发病率第一的恶性肿瘤[1],其中三阴性乳腺癌较其他类型乳腺癌相比,具有治疗棘手、预后更差的特点。"七损八益"是以阴阳损益之道来谈保身长全的理论思想。文章将结合"七损八益"的观点,从其损益转化的角度来讨论三阴性乳腺癌的治疗方法。其中以七损对应三阴性乳腺癌雌激素受体阴性,八益为应用雄激素受体治疗三阴性乳腺癌的手段。试以《内经》"七损八益"理论来探讨三阴性乳腺癌的关系,为研究治疗乳腺癌提供更多的思路。     

基于肝与雌激素相互关系探讨膀胱过度活动症

膀胱过度活动症是泌尿系的常见疾病,目前尚无理想的治疗方案。本文基于肝与雌激素相互关系论治膀胱过度活动症,从中医基础理论、膀胱过度活动症的病因病机、膀胱过度活动症与雌激素的关系、肝郁与雌激素的联系等方面进行阐述,为从肝郁-雌激素角度论治膀胱过度活动症提供依据。     

Menstrual and reproductive characteristics and breast cancer risk by hormone receptor status and ethnicity: The Breast Cancer Etiology in Minorities study

We pooled multiethnic data from four population-based studies and examined associations of menstrual and reproductive characteristics with breast cancer (BC) risk by tumor hormone receptor (HR) status [defined by estrogen receptor (ER) and progesterone receptor (PR)]. We estimated odds ratios and 95% confidence intervals using multivariable logistic regression, stratified by age (<50, ≥50 years) and ethnicity, for 5,186 HR+ (ER+ or PR+) cases, 1,365 HR− (ER− and PR−) cases and 7,480 controls. For HR+ BC, later menarche and earlier menopause were associated with lower risk in non-Hispanic whites (NHWs) and Hispanics, and higher parity and longer breast-feeding were associated with lower risk in Hispanics and Asian Americans, and suggestively in NHWs. Positive associations with later first full-term pregnancy (FTP), longer interval between menarche and first FTP and shorter time since last FTP were limited to younger Hispanics and Asian Americans. Except for nulliparity, reproductive characteristics were not associated with risk in African Americans. For HR− BC, lower risk was associated with later menarche, except in African Americans and older Asian Americans and with longer breast-feeding in Hispanics and Asian Americans only. In younger African Americans, HR− BC risk associated with higher parity (≥3 vs. 1 FTP) was increased fourfold in women who never breast-fed, but not in those with a breast-feeding history, suggesting that breast-feeding may mitigate the adverse effect of higher parity in younger African American women. Further work needs to evaluate why menstrual and reproductive risk factors vary in importance according to age and ethnicity.     

六味地黄汤干预抑郁大鼠学习记忆的作用机制

目的:探讨六味地黄汤对慢性抑郁大鼠记忆障碍的改善作用,并探讨其可能的作用机制。方法:Wistar雌性大鼠随机分为正常组(生理盐水)、慢性不可预见性温和应激(CUMS)模型组(生理盐水)、六味地黄汤低、中、高剂量组(2. 60,7. 81,23. 50 g·kg~(-1)·d~(-1))。除正常组外,其余各组造成CUMS模型。每周称体质量,观察其行为学指标变化;实时荧光定量聚合酶链式反应(Real-time PCR)检测其海马G蛋白偶联雌激素受体(GPR30),胞内磷脂酰肌醇激酶(PI3K),环磷酸腺苷反应元件结合蛋白(CREB),脑源性神经营养因子(BDNF) mRNA的表达;酶联免疫吸附测定(ELISA)检测血清中雌激素含量。结果:与正常组比较,模型组体质量、活动能力、兴趣等明显降低(P 0. 05,P 0. 01);与模型组比较,六味地黄汤2. 60,7. 81,23. 50 g·kg~(-1)可明显提高CUMS大鼠糖水偏好度(P 0. 01)和旷场实验的站立次数(P 0. 01);7. 81,23. 50 g·kg~(-1)明显提高旷场实验的总距离(P 0. 05,P 0. 01);2. 60,7. 81 g·kg~(-1)可缩短水迷宫实验寻台潜伏期(P 0. 01);7. 81 g·kg~(-1)可增加血清中雌激素含量(P 0. 05);CUMS模型组大鼠海马组织内的GPR30,PI3K,CREB,BDNF mRNA表达明显下降(P 0. 05,P 0. 01),六味地黄汤2. 60 g·kg~(-1)显著增加海马组织内的GPR30,CREB mRNA表达(P 0. 05,P 0. 01),7. 81 g·kg~(-1)明显增加海马组织内的GPR30,PI3K,CREB,BDNF mRNA表达量(P 0. 05,P 0. 01)。结论:六味地黄汤具有抗抑郁作用,逆转CUMS大鼠抑郁样行为及学习记忆障碍,其中中剂量组药效最显著。其作用机制可能与增加血清中雌激素和提高大鼠海马GPR30,PI3K,CREB,BDNF mRNA表达有关。     

三苯氧胺与来曲唑治疗ER阳性乳腺癌的临床疗效及对血清雌二醇水平和远期预后的影响

目的探讨三苯氧胺与来曲唑治疗雌激素受体(ER)阳性乳腺癌的临床疗效及对血清雌二醇(E2)水平和远期预后的影响。方法采用简单随机抽样法将110例ER阳性乳腺癌患者分为对照组(n=53)和研究组(n=57)。两组患者均接受长春瑞滨联合顺铂治疗,对照组患者在此基础上接受三苯氧胺治疗,研究组患者在此基础上接受来曲唑治疗,随访3年。比较两组患者的临床疗效、血清肿瘤标志物和E2水平、子宫内膜情况、不良反应发生率及生存情况。结果研究组患者的疾病控制率为92.98%,高于对照组的79.25%,差异有统计学意义(P<0.05)。治疗前,两组患者的血清糖类抗原153(CA153)、癌胚抗原(CEA)及E2水平比较,差异均无统计学意义(P>0.05)。治疗后3个月,两组患者的血清CEA和CA153水平均较本组治疗前降低,且研究组患者的血清CEA和CA153水平均低于对照组,差异均有统计学意义(P<0.05)。治疗后3、6、12个月,研究组患者的血清E2水平均低于治疗前,对照组患者的血清E2水平均高于治疗前,差异均有统计学意义(P<0.05)。病理结果提示,治疗后对照组中子宫内膜息肉2例,内膜不典型增生1例。两组患者恶心呕吐、便秘、肝肾功能不全、血小板减少、粒细胞减少及白细胞降低的发生率比较,差异均无统计学意义(P> 0.05)。研究组患者的3年生存情况优于对照组(P<0.05)。结论来曲唑治疗ER阳性乳腺癌的临床疗效优于三苯氧胺,且可降低血清肿瘤标志物和E2水平,改善远期预后。