妊娠相关性乳腺癌的化疗安全性评价

妊娠相关性乳腺癌因其特殊的生理改变以及治疗可能对胎儿产生影响等因素,在药物治疗上具有一定的复杂性和特殊性.2020年5月,中华医学会外科学分会乳腺外科学组发布妊娠相关性乳腺癌临床诊治专家共识(2020版),推荐蒽环类、紫杉烷类、环磷酰胺、铂类作为妊娠期乳腺癌的治疗药物,但未对其安全性进行分析,也未推荐可行的治疗方案.本...     

Patient reported outcomes in randomized controlled cancer trials in advanced disease: a structured literature review

Introduction: In advanced cancer quality of life (QoL) is the most important goal of care. It is measured by patient-reported-outcomes (PRO). This structured review evaluated how randomized controlled trials (RCTs) on anti-cancer therapy in advanced cancer reported PRO.

Methods: Search was performed in MEDLINE via PubMed for RCTs with median patient survival of ≤2 years. Reporting was rated with the Consolidated Standards of Reporting Trials (CONSORT) PRO extension.

Results: Of 370 retrieved publications, 117 were eligible, but only 30/117 (26%) reported PRO. QoL was most frequently measured (29/30). On average, 4.4 (SD 2.5) of the 14 CONSORT items were met.

Conclusion: PRO are insufficiently reported in advanced cancer trials. Yet, this is paramount to enable an informed and patient-oriented decision making process.     

乳腺癌的防治与临床治疗探讨

目的探讨乳腺癌临床诊治效果以及乳腺癌的防治。方法总结分析2006年5月～2008年10月来笔者所在医院就诊的60例乳腺癌患者的临床资料,在治疗的过程中根据患者的年龄、病理分期以及肿块的位置等选择手术方式。结果通过对本组60例乳腺癌患者临床实施手术后,全部病例均愈合出院,并且对本组全部患者3年以上随访可以得知,改良性根治手术3年生存率为94.12%,乳腺癌根治术3年患者生存率为84.62%。结论改良性根治手术是临床治疗乳腺癌的首先方法。并且加强对乳腺癌的防治,选择恰当的手术方法对提高乳腺癌患者的生存率具有重要的作用。     

长春新碱治疗乳腺癌的临床疗效观察

目的：探讨长春新碱在乳腺癌患者中的临床疗效。方法：选取2004年1月~2010年5月的184例乳腺癌患者为研究对象,将其根据化疗方式不同分为对照组（米托蒽醌组）92例和观察组（米托蒽醌联合长春新碱组）92例,后将两组患者的治疗总有效率、不良反应发生率及治疗后1个月和3个月的生存质量评分进行统计比较。结果：观察组的治疗总有效率及治疗后1个月和3个月的生存质量评分均高于对照组,P均〈0.05,差异有统计学意义,但两组患者不良反应发生率比较,P〉0.05,差异无统计学意义。结论：长春新碱在乳腺癌患者中的临床疗效好,不良反应未见升高,可改善患者的生存质量。     

Phase I safety,pharmacokinetic and pharmacodynamic studies of 2-methoxyestradiol alone or in combination with docetaxel in patients with locally recurrent or metastatic breast cancer

Summary Purpose: We report the first phase I trials of 2-methoxyestradiol (2ME2, Panzem? Capsules, EntreMed, Rockville, MD), alone and in combination with docetaxel, in patients with metastatic breast cancer (MBC). Patients and methods: In Trial 001, 2ME2 monotherapy was administered orally once (200–1000 mg/d, cohorts 1–5) or twice daily (200–800 mg/q12h, cohorts 6–9) for 28 days followed by a 14-day observation period, continuously thereafter. In Trial 002, docetaxel 35 mg/m² was administered weekly for four of six weeks for a maximum six cycles; 2ME2 (200–1000 mg/d) was given orally once daily for 28 days followed by a 13-day observation period in cycle one, continuously thereafter. In both trials, responding or stable patients continued 2ME2 until progression. Results: Trial 001 enrolled 31 patients; there were no objective responses. Trial 002 enrolled 15 patients; ORR was 20% including one CR. There were no Grade IV toxicities; MTD was not reached in either study. When combined with docetaxel, three patients had significant transaminase elevations that returned to normal with continued treatment (in two of three patients). There was significant inter-patient variability and extensive metabolism to 2-methoxyestrone (2ME1). Steady-state AUC and trough concentrations of 2ME2 increased linearly up to 400–600 mg/d; doses above 400–600 mg/d did not increase 2ME2 levels. The target trough concentration (3–25 ng/mL) was not attained. Combined administration did not alter docetaxel or 2ME2 pharmacokinetics. Conclusion: 2ME2, alone or in combination with docetaxel, was well tolerated in patients with MBC but systemic exposure remained below the expected therapeutic range.     

The use of electrocardiograms in clinical trials: a public discussion of the proposed ICH E14 regulatory guidance

This meeting, jointly sponsored by the FDA, Drug Information Association and Heart Rhythm Society, examined crucial issues on nonclinical and clinical evaluation of the potential of new drugs to prolong the QT interval of an electrocardiogram (ECG). It gathered ～ 350 attendees from pharmaceutical industry, academia, core ECG analysis laboratories, regulatory agencies (FDA, European Medicines Agency, Japanese Ministry of Health, Labour and Welfare, and Health Canada) and the International Conference on Harmonisation (ICH). Key issues discussed included the reliability of the S7B guideline strategy, design and usefulness of the ‘thorough QT/QTc study’ recommended by ICH E14 guideline, choice of 5 ms QTc prolongation as a threshold for regulatory concern, ECG reading, and statistical analysis. This report is restricted to the two main presentations dealing with the predictability of nonclinical tests for clinical outcomes – one defending the prognostic value of nonclinical tests and the other, from the FDA, which casts reservations on the predictive value of nonclinical studies. Commentary on the recent finalisation of ICH S7B and E14 guidelines are also provided.     

心理护理在乳腺癌手术患者护理工作的应用

目的：探讨心理护理应用在乳腺癌手术患者护理工作中的临床效果,为临床应用做出指导。方法选择我院自2010年1月～2013年1月收治的94例需行乳腺癌手术的患者为研究对象,完全随机分为两组。对照组给予常规护理,观察组在对照组的基础上加强患者的心理护理,对比观察两组患者的负面心理状态的发生情况以及对护理工作的满意情况。结果（1）观察组患者负面心理状态的发生率为17.02%（8/47）,明显低于对照组46.81%（22/47）,结果比较差异具有统计学意义（P＜0.05）;（2）观察组对护理工作的满意度为95.74%（45/47）,明显高于对照组80.85%（38/47）,结果比较差异具有统计学意义（P＜0.05）。结论心理护理应用在乳腺癌手术患者中的临床效果显著,可以降低患者负面心理状态的出现,增进医患关系,值得临床广泛推广。     

超声影像组学在乳腺癌中应用的研究进展

乳腺癌发病率逐年上升,且病死率占所有肿瘤中首位,已成为威胁女性健康的重要因素。早期诊断、早期治疗不仅可降低乳腺癌病死率,也可提高患者生存率及改善其生存质量。超声影像组学是一个新兴的研究领域,能从超声图像中提取可定量分析的高维数据。近年来,超声影像组学已广泛应用于乳腺癌的临床诊疗方面。本文就超声影像组学在乳腺癌诊断、分子分型及淋巴结转移情况评估等方面的研究进展进行综述。     

瘦素受体在乳腺癌组织中的表达及其与临床预后的关系

目的检测瘦素受体（ObR）在人乳腺癌组织中的表达情况,探讨其与HER-2以及临床病理之间的关系,并分析它们对预后的影响。方法用免疫组织化学的方法检测124例乳腺癌组织中ObR的表达,回顾分析相关的临床病理资料和随访情况。结果 ObR在大多数乳腺癌组织中均有表达,阳性率为82.3%。ObR表达与患者的年龄、绝经状态、肿瘤大小、肿瘤病理学分型、淋巴结转移均无关（P〉0.05）;与ER、PR、P53的表达状态也无关（P〉0.05）;ObR的表达与HER-2相关（P=0.011）;ObR阳性者与阴性者的总生存率检验（χ2=0.048,P=0.827）及无病生存率检验（χ2=2.829,P=0.093）差异均无统计学意义。结论 ObR与HER-2在乳腺癌中的表达具有相关性,可能是导致乳腺癌预后不良的因素。     

曲妥珠单抗相关心脏毒性1例并文献复习

1例45岁女性患者因确诊“左乳腺恶性肿瘤”,FISH检测HER-2阳性,在吡柔比星化疗6次后行紫杉醇＋曲妥珠单抗化疗,曲妥珠单抗起始周期为7d（4mg·kg-1）,化疗2次后周期改为21d（6mg·kg-1）,6个月后改为曲妥珠单抗单药21d方案化疗,18个月后患者出现胸闷、憋气症状,活动后明显,伴有双下肢水肿,心脏超声提示LVEF值33%。考虑该患者出现心功能不全与曲妥珠单抗的心脏毒性很可能相关。停用曲妥珠单抗化疗,予以去乙酰毛花甙强心、托拉塞米利尿、左卡尼汀营养心肌等治疗10d,患者症状完全消失,LVEF值恢复至45%,4个月后复查LVEF值恢复至51%。     

Patient-reported outcomes in moderate-to-severe allergic asthmatics treated with omalizumab: a systematic literature review of randomized controlled trials

Objective: Randomized controlled trials (RCTs) have established the safety and efficacy of omalizumab on clinical parameters, and have also evaluated its impact on patient-reported outcomes (PROs). The purpose of this systematic literature review was to review published data based on PRO endpoints in order to determine the benefit of omalizumab as add-on therapy to inhaled corticosteroids in patients with moderate-to-severe persistent allergic asthma.

Methods: A systematic literature review was conducted of reference databases and recent conferences. RCTs of add-on omalizumab therapy in adults, adolescents, and children with moderate-to-severe persistent asthma were included. Two researchers independently screened and reviewed articles with regards to inclusion and exclusion criteria for relevant studies.

Results: Twenty-six trials met the criteria for inclusion. Of these, PRO measures were included in 19 trials to capture the impact of omalizumab on symptoms, 11 assessed patients for health-related quality-of-life (HRQoL), and four evaluated asthma control. Other PROs related to global evaluation of treatment effectiveness and work productivity. Overall, results demonstrated a significant difference across most PROs in favor of omalizumab add-on therapy vs placebo or comparators.

Conclusions: PROs are an integral part of outcome assessment in clinical trials related to asthma. The RCTs reviewed demonstrate that omalizumab treatment improves PROs in patients with moderate-to-severe persistent allergic asthma, particularly symptom control and HRQoL.     

新辅助化疗在乳腺癌患者中应用的有效性研究

目的研究新辅助化疗在乳腺癌患者中应用的有效性,为乳腺癌的治疗提供临床依据。方法2008年1月-2010年1月来本院进行住院治疗的120例乳腺癌患者随机分为治疗组和对照组各60例,其中治疗组给予新辅助化疗后进行手术治疗,对照组只进行手术治疗。结果术后3个月和术后6个月治疗组CR比例明显高于对、照组差异有统计学意义（P〈0．05）,而对照组PD比例明显高于治疗组,差异具有统计学意义（P〈0．05）,并且两组患者的局部复发、远处转移、总生存比例、无瘤生存比例差异均无统计学意义（P〉0．05）。结论新辅助化疗能明显提高手术治疗的临床疗效,但是对于远期生存率的改善情况应当进一步研究。     

Lapatinib for breast cancer: a review of the current literature

Importance of the field: The identification of HER-2 expression as a predictive and prognostic marker revolutionized breast cancer. Trastuzumab, a humanized mAb, improves survival in both early and advanced HER-2 overexpressing breast cancer. However, many cancers either do not respond or develop resistance to this agent. Lapatinib is an oral tyrosine kinase inhibitor which has both HER-1 and -2 activities and has been licensed for use in recurrent breast cancer that overexpresses HER-2. Studies of lapatinib in early breast cancer are ongoing.

Areas covered in this review: A PubMed search was conducted using ‘lapatinib’ and ‘breast cancer’ as the key words. All published works up to July 2010 were reviewed. A manual review of abstracts presented at the ASCO Annual meeting and the San Antonio Breast Cancer Symposium was conducted for the last 2 years. In this review, we summarize the current knowledge of lapatinib and pose questions which need to be addressed as we further expand our knowledge of the HER-2 subtypes of breast cancer.

What the reader will gain: The reader will gain an up-to-date and comprehensive review of the current literature as it pertains to the safety and efficacy of lapatinib in the treatment of breast cancer.

Take home message: Lapatinib has provided an alternative for the treatment of advanced HER-2 overexpressing breast cancer and is currently being assessed in early disease.     

The chemotherapeutic potential of doxorubicin-loaded PEG-b-PLGA nanopolymersomes in mouse breast cancer model

Vesicles of mPEG-PLGA block copolymer were developed to deliver a therapeutic quantity of doxorubicin (DOX) for breast cancer treatment. The DOX-loaded nanoparticles (NPs) were prepared by the pH-gradient method and then evaluated in terms of morphology, size, DOX encapsulation efficiency and in vitro drug release mechanism.The PEG-PLGA nanopolymersomes were 134 ± 1.2 nm spherical NPs with a narrow size distribution (PDI = 0.121). DOX was entrapped in mPEG-PLGA nanopolymersomes with an encapsulation efficiency and a loading content of 91.25 ± 4.27% and 7.3 ± 0.34%, respectively. The DOX-loaded nanopolymersomes were found to be stable, demonstrating no significant change in particle size and encapsulation efficiency (EE%) during the 6-month storage period of the lyophilized powder at 4 °C. The nanopolymersomes sustained the release of DOX. In cytotoxicity studies of 4T1 cell line samples, free DOX showed a higher cytotoxicity (IC50 = 1.76 μg/mL) than did DOX-loaded nanopolymersomes (15.82 μg/mL) in vitro. In order to evaluate the antitumor efficacy and biodistribution of DOX-loaded nanopolymersomes, murine breast tumors were established on the BALB/c mice, and in vivo studies were performed. The obtained results demonstrated that the prepared drug delivery system was highly effective against a murine breast cancer tumor model and successfully accumulated in the tumor site through an enhanced permeation and retention mechanism.In vivo studies also proved that DOX-loaded nanopolymersomes are stable in blood circulation and could be considered a promising and effective DOX delivery system for breast cancer treatment.     

乳腺癌微创检查在临床中的应用

材料与方法47例病人均为女性,年龄在35~48岁,平均42岁。采用自身对照,其中术前临床分期为T1N1M02例, T2N1M010例, T3N1M012例, T3N2M018例。操作方法:乳腺局部皮肤常规消毒,左手指固定肿块,右手持注射器,针尖对准肿块中心部位,角度稍斜,针刺到肿块中心点,不穿透肿块,针头在肿块     

Cystatin M在乳腺癌中的表达及其临床意义

目的 了解cystatin M在乳腺肿瘤中的表达及其临床意义.方法 采用实时定量PCR检测52例乳腺肿瘤标本及邻近正常乳腺组织中cystatin M mRNA及内参GAPDH表达水平,分析cystatin M基因表达与临床病理参数的关系.结果 乳腺癌标本的cystatin M含量与其周围邻近的正常乳腺组织及良性肿瘤中表达cystatin M含量无统计学意义;但发生淋巴结转移的乳腺肿瘤标本的cystatin M则明显低于其周围邻近的正常乳腺组织(P＜0.05),也明显低于未发生淋巴结的乳腺肿瘤标本(P＜0.05);乳腺癌标本cystatin M表达水平与乳腺癌病人的雌激素受体状态(ER)及孕激素状态(PR)无关.结论 Cystatin M是一种监测乳腺癌是否发生转移的一种可靠的指标.     

乳腺癌患者癌胚抗原检测的临床意义

目的探讨癌胚抗原(CEA)检测在乳腺癌诊断和判断预后中的作用。方法应用免疫组化方法检测64例乳腺癌、37例正常及良性病变中癌胚抗原的表达。结果乳腺癌中癌胚抗原的阳性率(68.8%)明显高于正常对照组(16.2%),有显著性差异(P<0.05)。乳腺癌有淋巴结转移的癌胚抗原的阳性率(81.3%),略高于乳腺癌没有淋巴结转移的癌胚抗原的阳性率(56.3%),无显著性差异。结论癌胚抗原的检测有助于乳腺癌的诊断,癌胚抗原可能是判断乳腺癌预后的重要指标。     

The clinical significance of Ki-67 as a marker of prognostic value and chemosensitivity prediction in hormone-receptor-positive breast cancer: a meta-analysis of the published literature

Abstract

Objectives:

Hormone-receptor (HR)-positive breast cancer is associated with a poor response to adjuvant chemotherapy. Thus, it is important to identify HR-positive patients who can benefit from chemotherapy and the Ki-67 index may help to predict chemotherapy efficacy in such populations. However, controversies exist regarding the prognostic and predictive role of Ki-67 and its exact cut-off value in HR-positive patients. Therefore, we conducted this study.