Underutilisation of breast cancer prevention medication in Australia

Increased implementation of proven prevention strategies is required to combat rising breast cancer incidence. We assessed use of risk reducing medication (RRMed) by Australian women at elevated breast cancer risk. Only 2.4% had ever used RRMed. Higher breast cancer risk was statistically significantly associated with use of RRMed (OR 1.82, 95%CI: 1.08–3.07, p = 0.02 for ≥30% lifetime risk compared with 16%–29% lifetime risk), but parity, education level and family history of breast cancer were not. Breast cancer prevention medications are underutilised. Efforts are needed to incorporate breast cancer risk assessment and risk management discussions into routine health assessments for women.     

Evaluation of progressive hepatic histopathology in long-term tamoxifen therapy

Tamoxifen (TAM) therapy is the better treatment for breast cancer and the drug use the prophylaxis of this disease in young premenopausal women. Yet, the effects associated with this therapy are unknown. To better understand the extension of this problem, we developed an animal model to mimic this therapy, aiming to evaluate its potential biochemical and histopathological changes in the liver. Young cycling female rats were treated with TAM for one, two and three months and toxicological biomarkers and liver histomorphometry were evaluated. Starting at two months, TAM-treatment prevented the normal age-dependent increase in body weight, without inducing changes in food intake. Serum levels of cholesterol and of the metabolic enzymes creatine kinase and aspartate aminotransferase were reduced in all TAM treatment periods. Serum levels of the metabolic enzymes alkaline phosphatase and lactate dehydrogenase were increased after the first month but returned to control levels upon 3 months of drug exposition. Moderate microvesicular steatosis, classified only at the first month of TAM treatment, was reduced afterwards. Our model showed an adaptive response of liver upon 3 months of treatment, suggesting that at the stated conditions, TAM will not promote hepatotoxicity. In this way, the present model may be useful in the study of possible key endocrine effects of TAM use and the search for better clinical outcomes.     

消乳散结胶囊联合他莫昔芬治疗乳腺增生症的疗效观察

目的 研究瑞香狼毒Stellera chamaejasme花中黄酮和木脂素类化学成分及其抗氧化活性,分析构效关系。方法 利用大孔吸附树脂、正反相硅胶、Sephadex LH-20等色谱分离材料,通过柱色谱和高效液相色谱等分离方法进行分离纯化,运用核磁共振（NMR）、质谱（MS）等波谱技术鉴定化合物结构,并采用FRAP法、DPPH法和ABTS法对分离得到的化合物进行体外抗氧化活性测试。结果 从瑞香狼毒花甲醇提取物中分离鉴定了12个化合物,分别鉴定为艾黄素（1）、槲皮素（2）、isoscutellarein-8-O-β-D-glucuronopyranoside（3）、槲皮素-3-O-β-D-葡萄糖苷（4）、紫云英苷（5）、hypolaetin-8-O-β-D-glucuronopyranoside（6）、kaempferol 3-O-β-D-glucopyranosyl-（1→2）-O-α-L-xylopyranoside（7）、rel-（3R,3''S,4R,4''S）-3,3'',4,4''-tetrahydro-6,6''-dimethoxy[3,3''-bi-2H-benzopyran]-4,4''-diol（8）、马台树脂醇（9）、乌拉尔醇（10）、环黄芪醇（11）、松脂醇（12）。抗氧化活性实验表明,黄酮和木脂素类化合物均显示了较强的抗氧化活性。结论 化合物1、3、5～7和10为首次从该植物中分离得到;化合物2、4、5和10表现出显著的抗氧化活性,其中黄酮类化合物C-3或C-8位连有糖链会降低其抗氧化活性。     

他莫昔芬联合人绒毛膜促性腺激素对反复种植失败患者冻融周期子宫内膜容受性的影响

目的:探讨他莫昔芬联合人绒毛膜促性腺激素(HCG)对反复种植失败(repeated implantation failure,RIF)患者冻融周期子宫内膜容受性的影响。方法:回顾性选取2017年7月至2019年6月海南省妇女儿童医学中心RIF(≥3次)再次进行冻融胚胎移植的188例患者的临床资料,根据子宫内膜准备方法不同分为观察组105例和对照组83例。观察组患者采用他莫昔芬联合HCG宫腔灌注,对照组患者采用来曲唑联合HCG宫腔灌注。比较两组患者子宫内膜厚度与内膜下血流情况[搏动指数(PI)、阻力指数(RI)]、子宫内膜血流分型、HCG日与移植日激素[黄体生成素(LH)、雌二醇(E2)及孕酮]水平及妊娠结局的差异。结果:移植日,两组患者子宫内膜厚度较促排卵前增加,且观察组患者明显大于对照组,差异均有统计学意义(P<0.05);两组患者PI、RI均较促排卵前降低,观察组患者明显低于对照组,差异均有统计学意义(P<0.05)。观察组子宫内膜血流A型患者占比为80.95%(85/105),明显高于对照组的40.96%(34/83),差异有统计学意义(P<0.05)。观察组患者HCG日与移植日的E2水平明显高于对照组,HCG日LH水平明显低于对照组,差异均有统计学意义(P<0.05)。观察组患者胚胎着床率、临床妊娠率明显高于对照组,差异均有统计学意义(P<0.05)。结论:他莫昔芬联合HCG治疗可有效改善RIF患者冻融周期子宫内膜容受性,增加子宫内膜厚度,提高妊娠率。     

Results from a randomized trial of a web-based,tailored decision aid for women at high risk for breast cancer

Objective

To assess the impact of Guide to Decide (GtD), a web-based, personally-tailored decision aid designed to inform women's decisions about prophylactic tamoxifen and raloxifene use.

Methods

Postmenopausal women, age 46–74, with BCRAT 5-year risk ≥1.66% and no prior history of breast cancer were randomized to one of three study arms:intervention (n = 690), Time 1 control (n = 160), or 3-month control (n = 162). Intervention participants viewed GtD prior to completing a post-test and 3 month follow-up assessment. Controls did not. We assessed the impact of GtD on women's decisional conflict levels and treatment decision behavior at post-test and at 3 months, respectively.

Results

Intervention participants had significantly lower decisional conflict levels at post-test (p < 0.001) and significantly higher odds of making a decision about whether or not to take prophylactic tamoxifen or raloxifene at 3-month follow-up (p < 0.001) compared to control participants.

Conclusion

GtD lowered decisional conflict and helped women at high risk of breast cancer decide whether to take prophylactic tamoxifen or raloxifene to reduce their cancer risk.

Practice implications

Web-based, tailored decision aids should be used more routinely to facilitate informed medical decisions, reduce patients’ decisional conflict, and empower patients to choose the treatment strategy that best reflects their own values.     

诱导型成骨细胞特异Stat3基因敲除小鼠的构建及验证

目的：运用Cre-Loxp基因敲除系统,构建诱导型条件性Stat3基因敲除小鼠并验证其敲除效率。方法：通过Stat3^fl/fl与Col1 creERT2基因型的C57小鼠多代杂交,构建诱导型成骨细胞特异Stat3敲除小鼠Stat3^Col1ERT2。取其骨髓间充质干细胞（bone mesenchymal stem cells, BMSCs）,加入4-羟基他莫西芬（4-OTH）后,采用实时定量PCR技术和免疫印迹技术在mRNA与蛋白水平分别体外验证Stat3敲除效果。于小鼠腹腔注射他莫昔芬,采用免疫荧光染色技术,观察小鼠上颌牙槽骨区域STAT3的表达,以体内验证敲除效果。采用SPSS 24.0软件包对数据进行统计学分析。结果：实时定量PCR和免疫印迹结果显示,Stat3^Col1ERT2小鼠BMSCs体外加药诱导敲除后,STAT3的mRNA水平显著下调（P<0.05）、蛋白表达降低（P<0.05）。免疫荧光染色结果显示,Stat3^Col1ERT2小鼠体内上颌牙槽骨区域成骨细胞的STAT3表达显著降低（P<0.05）。结论：本研究成功构建了诱导型成骨细胞特异Stat3基因敲除小鼠,使基因敲除可受观察者时空调控,为今后正畸牙移动、颌骨牵引成骨、颌骨骨折等牙槽骨改建机制的研究提供了新的思路及依据。     

不同类型内分泌药物治疗对乳腺癌患者骨代谢的影响

目的 观察不同类型内分泌药物治疗对乳腺癌患者术后骨代谢水平的影响。方法 收集2013年5月至2019年1月南方医科大学附属小榄医院治疗的乳腺癌患者239例,按照内分泌治疗药物不同分为A组（采用他莫昔芬治疗,75例）、B组（采用氟维司群治疗,83例）和C组（采用依西美坦治疗,81例）。比较各组治疗前及治疗12个月降钙素（CT）、骨钙素（BGP）、骨碱性磷酸酶（BAP）和甲状旁腺素（PTH）水平,同时检测各组腰椎骨密度（BMP）并比较。结果 治疗前,三组CT、BGP、BAP、PTH和BMP值比较,差异均无统计学意义（P>0.05）;治疗后,三组CT均不同程度升高,其中C组升幅最大,A组升幅最小,组间差值比较,差异有统计学意义（P=0.009）;三组BGP均不同程度升高,其中A组升幅最大,B组升幅最小,组间差值比较,差异有统计学意义（P=0.005）;三组BAP均不同程度降低,其中B组降幅最大,A组降幅最小,组间差值比较,差异有统计学意义（P=0.018）;三组PTH均不同程度降低,其中C组降幅最大,A组降幅最小,组间差值比较,差异有统计学意义（P=0.025）。治疗后,A组腰椎BMP未见明显降低,但C组腰椎BMP下降较明显,三组间BMP治疗前后差值比较,差异有统计学意义（P=0.022）。结论 不同内分泌治疗药物均可导致乳腺癌患者BMP降低,但他莫昔芬对患者骨代谢水平影响程度较小。     

他莫昔芬体外促进HepG2细胞脂肪变性观察

目的：研究他莫昔芬（TAM）对体外培养的HepG2细胞脂肪变性以及脂类代谢调控关键因子表达的影响。方法应用油酸（50μmol/L）处理HepG2细胞,诱导细胞脂肪变性体外模型,同时给予不同浓度的TAM （5～20μmol/L）干预72 h;采用油红O染色和甘油三酯含量测定检测HepG2细胞内脂质聚集情况;应用蛋白印迹法检测固醇调节元件结合蛋白-1c（SREBP-1c）、脂肪酸合成酶（FAS）、硬脂酰辅酶A去饱和酶（SCD）、肉酯软脂酰基转移酶（CPT1）和微粒体甘油三酯转移蛋白（MTP）的表达;采用细胞活性检测试剂盒测定细胞活性。结果在干预72 h后,模型组细胞内甘油三酯含量为（16.53＆#177;0.17） mg/100 mg蛋白质,在5μmol/L TAM处理细胞内甘油三酯含量为（17.77＆#177;0.05） mg/100mg蛋白质,与模型组无显著性差异,但在10μmol/L和20μmol/L TAM处理组较模型组分别增加了31%[（21.57＆#177;0.16） mg/100 mg蛋白质]和44%[（23.82＆#177;0.44） mg/100 mg蛋白质],（P＆lt;0.05）;TAM上调细胞内SREBP-1c、FAS、SCD和MTP蛋白表达,但并不改变CPT1蛋白表达;TAM在5～20μmol/L范围内不影响HepG2细胞活性。结论 TAM可促进油酸诱导的HepG2细胞脂肪变性,其主要机制可能是通过上调SREBP-1c及其下游基因,如FAS和SCD的表达而增加了脂肪酸的合成。     

Goserelin plus tamoxifen compared to chemotherapy followed by tamoxifen in premenopausal patients with early stage-, lymph node-negative breast cancer of luminal A subtype

ObjectivesTo study the outcomes of adjuvant goserelin combined with tamoxifen (GosTam) compared to chemotherapy followed by tamoxifen (ChemTam) in premenopausal patients with early stage, luminal A breast cancer.MethodsFrom 2008 until 2013, data were retrospectively collected for premenopausal patients who underwent surgery for invasive tumors that were ≤2.0 cm, node-negative, strongly positive for estrogen and progesterone receptors, HER-2-negative, and Ki-67 < 25%. The patients were divided into two groups according to adjuvant regimen, either GosTam or ChemTam. All patients who underwent different adjuvant regimens were excluded.ResultsIn total, 235 patients underwent GosTam and 171 patients underwent ChemTam. There were significantly more patients younger than 40 years in the GosTam group (32% GosTam vs. 22% ChemTam, p = 0.031). Mean tumor size was significantly smaller (1.19 cm vs. 1.48 cm, p < 0.001), Ki-67 significantly lower (p = 0.049), and nuclear grade was low in a significant number of patients in the GosTam group (2% vs. 13%, p < 0.001). After a median follow-up of 51.3 months, there was no mortality in either group. There was no significant difference in 5-year disease-free survival (DFS) between the two groups even after univariate analysis considering age, tumor size, nuclear grade, and P53% (GosTam = 98.9% vs. ChemTam = 95.7%, HR = 0.404, 95% CI = [0.073, 2.222], p = 0.248).ConclusionThere was no difference between treatment groups, and neither chemotherapy nor ovarian suppression seemed to improve the outcome. Thus, tamoxifen alone might be a sufficient option for this low-risk patient population.