Early prediction of pathological outcomes to neoadjuvant chemotherapy in breast cancer patients using automated breast ultrasound

Objective： Early assessment of response to neoadjuvant chemotherapy （NAC） for breast cancer allows therapy to be individualized. The optimal assessment method has not been established. We investigated the accuracy of automated breast ultrasound （ABUS） to predict pathological outcomes after NAC. Methods： A total of 290 breast cancer patients were eligible for this study. Tumor response after 2 cycles of chemotherapy was assessed using the product change of two largest perpendicular diameters （PC） or the longest diameter change （LDC）. PC and LDC were analyzed on the axial and the coronal planes respectively. Receiver operating characteristic （ROC） curves were used to evaluate overall performance of the prediction methods. Youden＇s indexes were calculated to select the optimal cut-off value for each method. Sensitivity, specificity, positive and negative predictive values （PPV and NPV） and the area under the ROC curve （AUC） were calculated accordingly.Results： ypT0/is was achieved in 42 patients （14.5%） while ypT0 was achieved in 30 patients （10.3%） after NAC. All four prediction methods （PC on axial planes, LDC on axial planes, PC on coronal planes and LDC on coronal planes） displayed high AUCs （all〉0.82）, with the highest of 0.89 [95% confidence interval （95% CI）, 0.83-0.95] when mid-treatment ＆BUS was used to predict final pathological complete remission （pCR）. High sensitivities （85.7%-88.1%） were observed across all four prediction methods while high specificities （81.5%-85.1%） were observed in two methods used PC. The optimal cut-off values defined by our data replicate the WHO and the RECIST criteria. Lower AUCs were observed when mid-treatment ABUS was used to predict poor pathological outcomes. Conclusions：ABUS is a useful tool in early evaluation of pCR after NAC while less reliable when predicting poor pathological outcomes.

Evaluation of menopausal status among breast cancer patients with chemotherapy-induced amenorrhea

Objective： In patients with chemotherapy-induced amenorrhea （CIA）, the menopausal status is ambiguous anddifficult to evaluate. This study aimed to establish a discriminative model to predict and classify the menopausalstatus of breast cancer patients with CIA.Methods： This is a single center hospital-based study from 2013 to 2016. The menopausal age distribution andaccumulated incidence rate of CIA are described. Multivariate models were adjusted for established and potentialconfounding factors including age, serum concentration of estradiol （E2） and follicle-stimulating hormone （FSH）,feeding, pregnancy, parity, abortions, and body mass index （BMI）. The odds ratio （OR） and 95% confidenceinterval （95% CI） of different risk factors were estimated.Results： A total of 1,796 breast cancer patients were included in this study, among whom, 1,175 （65.42%） werepremenopausal patients and 621 （34.58%） were post-menopause patients. Five hundred and fifty patients wereincluded in CIA analysis, and a cumulative CIA rate of 81.64% was found in them. Age （OR： 1.856, 95% CI：1.732-1.990）, serum concentration of E2 （OR： 0.976, 95% CI： 0.972-0.980） and FSH （OR： 1.060, 95% CI：1.053-i.066）, and menarche age （OR： 1.074, 95% CI： 1.009-1.144） were found to be associated with the patients＇menopausal status. According to multivariate analysis, the discriminative model to predict the menopausal status isLogit （P）=-28.396＋0.536Age-0.014E2＋0.031FSH. The sensitivities for this model were higher than 85%, and itsspecificities were higher than 89%.Conclusions： The discriminative model obtained from this study for predicting menstrual state is important forpremenopausal patients with CIA. This model has high specificity and sensitivity and should be prudently used.

Fatigue and Quality of Life of Women Undergoing Chemotherapy or Radiotherapy for Breast Cancer

OBJECTIVE To examine fatigue and quality of life (QOL) inbreast cancer patients undergoing chemotherapy or radiotherapy.METHODS A self-report survey derived from the Chineseversion of Brief Fatigue Inventory, the Functional Assessmentof Chronic Illness Therapy for Breast Cancer, and the MedicalOutcomes Study Social Support Survey. Descriptive statisticswas used to examine the intensity of fatigue and the prevalenceof severe fatigue. Multivariate analysis of variance was used todetermine factors that affect the five domains of QOL among theparticipants.RESULTS The majority of the participants (n = 261) perceiveda mild level of fatigue, but 35.6% of them suffered severe fatigue.Fatigue had a significantly negative association with all domainsof QOL except social/family wellbeing. The participants whowere receiving chemotherapy, undergoing curative treatment andhaving inadequate social support were more likely to have poorerQOL in all five domains (after adjustment for age).CONCLUSION Although the majority of the participantsexperienced a mild level of fatigue, there was a substantial groupof breast cancer patients who perceived their fatigue as severe. Thefindings of this study showed that fatigue had a detrimental effecton the various aspects of the participants' QOL. Demographic andclinical characteristics of breast cancer patients who were at riskof getting poorer QOL were identified. The results of the studydemonstrate that we should enhance healthcare professionals'awareness of the importance of symptom assessment, andprovide them with information for planning effective symptom-management strategies among this study population.

THE CLINICAL COURSE AND TREATMENT RESULTS OF LUNG METASTASES FROM BREAST CANCER

Objective: To analyze the clinical course and treatment result of lung metastases from breast cancer Method: 122 cases with lung metastases from breast cancer were treated with chemotherapy or chemotherapy plus endocrine therapy, response was assessed according to WHO criteria and survival rate estimated using the life Table Results: The median time from initial treatment of primary tumor to lung metastases was 22 months Sites of common consecutive metastases were lung, liver and bone The overall response rate was 48% with a CR rate of 15% Compared to non DDP encompassing regimen, the CR rate was higher in DDP based chemotherapy (7% versus 21%, P <0 05) with a longer median survival time (MST) The PR rate was higher in regimens containing anthracycline (48%) than in those without anthracycline (20%, P <0 01) The response rate was similar between chemotherapy and chemotherapy plus endocrine therapy ( P >0 05) No difference in MST was observed between patients receiving anthracycline and non anthracycline encompassing regimens The 1 , 3 , 5 , and 10 year survival rate was 77%, 22%, 11%, and 10%, respectively Conclusion: Size of primary tumor, the length of disease free interval, the number of lung metastases may provide additional information for predicting patients survival after treatment of lung metastases Combination chemotherapy, especially DDP based chemotherapy may prolong survival time of patients with lung metastases from breast cancer

Trans-arterial chemoperfusion for the treatment of liver metastases of breast cancer and colorectal cancer: Clinical results in palliative care patients

AIM To evaluate the clinical value and efficiency of transarterial chemoperfusion(TACP) in patients with liver metastases from breast cancer(BC) and colorectal cancer(CRC).METHODS We treated 36 patients with liver metastases of BC(n = 19, 19 females) and CRC(n = 17; 8 females, 9 males) with repeated TACP. The treatment interval was 4 wk. TACP was performed with gemcitabine(1000 mg/m2) and mitomycin(10 mg/m2), administered within 1 h after positioning the catheter tip in the hepatic artery. Before treatment, the size, location, tumour volume, vascularization and number of liver tumours were evaluated using magnetic resonance imaging(MRI). Tumour response was evaluated according to the Response Evaluation Criteria in Solid Tumors guidelines.RESULTS TACP using gemcitabine and mitomycin for metastases from CRC and BC was performed without any serious side effects. The follow-up MRI showed a therapeutic response in 84.2% of the BC patients-stable disease 47.4% and partial response 36.8%. A progression was seen in 15.8%.CRC patients showed a therapeutic response in 52.9% of cases. A progression of the disease was documented in 47.1% of the patients with CRC. These data show that TACP in patients with liver metastases of BC leads to a significantly better therapeutic response compared with CRC patients(P = 0.042). The median survival time was 13.2 mo for the BC patients, which is significantly longer than for CRC patients at 9.3 mo(P = 0.001).CONCLUSION TACP for liver metastases of BC appears to be a safe and effective palliative treatment with improved outcomes in comparison to patients with CRC.

EFFECT OF DRUG-RESISTANCE REVERSORS ON EXPRESSIONS OF ONCOGENES OR TUMOR SUPPRESSOR ONCOGENES OF HUMAN TUMOR CELL LINES

MIT method was applied to assay the cytotoxicityof three reversors, verapamil (VER), dipyridamole (DPM)and cyclosporin (CSA) in K562, K562/ADM and KB celllines. S-P immunocytochemical technique was applied todetect cxpressions of oncoproteins or tumor suppressoroncoproteins in these tumor cell lines before or aftertreatment with these reversors. Results showed that threereversors were capable of inhibiting to a certain extentgrowth of K562 or KB cell lines and reversing greatlyadriamycin (ADM)-resistance in K562/ADM cell line.DPM and CsA were observed to inhibit, partly or wholly,expressions of p53, p16, bcl-2, p21 or cerbB-2oncoproteins. VER showed whole inhibition ofexpressions of P53, p16, p21 and bcl-2 and partlyexpression of p53 oncoprotein in K562 cell line. Theseresults suggest that growth inhibition in K562 or KB celllines by the reversors may be associated with partial orwhole inhibition or expressions of p53, p16, p21 or c-erbB-2 oncoproteins. Inhibitions of expressions p53, p16,p21 oncoproteins by VER but not DPM or CsA, may berespossible for reversing activity of VER for ADM-resistance in K562/ADM cell line.

泰索帝联合吡柔比星治疗晚期乳腺癌的疗效观察

目的:观察泰索帝联合吡柔比星治疗晚期乳腺癌临床疗效及不良反应。方法:26例均有组织病理学或细胞学诊断及可评价客观指标。采用泰索帝75mg/m2d1,静脉滴注1小时,用泰索帝前1天口服地塞米松10mg,连续3天。吡柔比星40mg/m2d2化疗。21天为1周期,2个周期评价疗效。结果:26例可评价疗效和不良反应。CR3例,PR16例,NC5例,PD2例,有效率73.1%。不良反应主要为白细胞减少Ⅲ度占34.6%,Ⅳ度占26.9%,脱发Ⅱ度占46.2%,Ⅲ度占23.1%,腹泻Ⅱ度占34.6%,Ⅲ度占23.1%。结论:泰索帝联合吡柔比星治疗晚期乳腺癌有效率较高,不良反应可以耐受。

“乳癌术后方”抗高转移小鼠乳腺癌作用机制的研究

目的:初步探讨治疗乳腺癌的作用机制是否与调节机体免疫功能有关。方法:采用4T1乳腺癌小鼠为实验模型,口服中药"乳癌术后方",观察其抑瘤及抗肺转移作用,并对荷瘤小鼠T细胞增殖功能、T细胞表型及细胞因子IL-10、IL-12、IFNγ-等免疫指标进行检测。结果:实验显示"乳癌术后方"对荷瘤小鼠瘤体积抑制率及肺转移抑制率分别为42.70%、13.14%,与模型组相比能显著抑制肿瘤生长(P<0.01);中药与CTX同时使用还能将CTX的抑瘤率再提高13%(P<0.01),肺转移抑制率再提高近10%。与模型组相比,"乳腺癌术后方"能明显上调荷瘤小鼠T细胞和B细胞活性,下调巨噬细胞百分比,明显增强T淋巴细胞增殖能力(P<0.01),并能抑制荷瘤小鼠淋巴细胞IL-10的生成,增强IFNγ-及IL-12的产生,使之更接近正常小鼠水平。结论:"乳癌术后方"的抗肿瘤作用可能是通过减轻荷瘤宿主的免疫抑制、增强机体抗肿瘤免疫反应来实现的。

不同新辅助化疗方案对三阴性乳腺癌治疗疗效临床分析

目的观察新辅助化疗提高三阴性乳腺癌（TNBC）手术切除的近期疗效及3种不同新辅助化疗方案的治疗效果.方法 150例局部晚期TNBC患者随机分为3组,每组各50例,A组采取TAC（多西他赛＋表阿霉素＋环磷酰胺）方案,B组采取TC（多西他赛＋环磷酰胺）方案,C组采取CEF（表阿霉素＋氟尿嘧啶＋环磷酰胺）进行新辅助化疗,观察化疗后近期疗效与不良反应.结果 TAC组有效率为92.0%,TC组为84.0%,CEF组为76.0%,3组化疗方案1~5周期均使同侧腋淋巴结缩小,且TAC组优于TC、CEF组（P〈0.05）,3组中不良反应因予预防干预,均较少.结论 TNBC对多西他赛＋表阿霉素＋环磷酰胺较多西他赛＋环磷酰胺及表阿霉素＋氟尿嘧啶＋环磷酰胺新辅助化疗更敏感,更易获c CR.

法乐通治疗晚期乳腺癌临床总结

目的：考察法乐通治疗晚期绝经后乳腺癌的疗效及其不良反应。方法：法乐通一线治疗每日一次６０ｍｇ口服，二线治疗每日一次１２０ｍｇ口服。结果：共６０例，有效率１８３％。一线治疗１８例，有效率３３３％。二线治疗４２例，有效率１１９％。淋巴结和骨转移疗效较好，肝转移、肺转移及胸壁转移也有一定疗效。一线治疗较二线治疗、未用内分泌治疗较曾用内分泌治疗、绝经时间长（≥１０年）较绝经时间短（＜１０年）以及疗后无瘤间期长（≥５年）较疗后无瘤间期短（＜５年）疗效好，不良反应轻微，主要为恶心、纳差。结论：法乐通是治疗晚期绝经后乳腺癌有效和安全的抗雌激素抗肿瘤新药。

东北菱提取物对肝癌细胞的体内外抑制作用

目的 :探索东北菱提取物对肝癌细胞体内外抑制作用。方法 :采用 3H- Td R掺入法分别测定东北菱醇提取物和水提取物对肝癌细胞的体外敏感性 ;对荷瘤小鼠进行体内实验 ,观察该提取物对肝癌细胞生长的抑制率。结果 :体外实验当剂量达 2 2 5 .0 0 g· L- 1 时 ,抑制率为 75 .4 9% ;体内实验抑瘤率为 6 0 %以上。结论 :东北菱不同溶剂提取物均具有抑制肝癌细胞的作用。

TAC、TEC方案新辅助化疗治疗乳腺癌效果比较

目的比较TAC、TEC两种新辅助化疗方案治疗乳腺癌的疗效。方法 139例原发性乳腺癌患者,随机分为TAC组71例和TEC组68例,分别采用TAC（多西他赛＋吡柔比星＋环磷酰胺）方案及TEC（多西他赛＋表柔比星＋环磷酰胺）方案进行4~6周期的新辅助化疗,观察肿瘤、腋窝淋巴结的变化以及不良反应发生情况。结果 TAC组总有效率（RR）、病理完全缓解率（pCR）、临床完全缓解率（cCR）、临床部分缓解率（cPR）以及病情稳定（SD）率分别为88.7%、11.3%、28.2%、60.6%和11.3%,TEC组分别为86.8%、10.3%、26.5%、60.3%和13.2%,两组相比P均〉0.05。化疗过程中两组白细胞下降、血小板减少、便秘、心脏毒性、肝肾功能异常发生率相比P均〉0.05。TAC组胃肠道反应（恶心或呕吐）发生率为46.5%,低于TEC组的66.2%（P〈0.05）。两组手术切除率均达100%。结论用TAC、TEC方案行乳腺癌新辅助化疗疗效满意,不良反应少。

紫杉醇联合顺铂治疗57例晚期乳腺癌的临床疗效分析

目的:观察紫杉醇联合顺铂(DDP)方案治疗晚期乳腺癌(ABC)及蒽环类耐药性乳腺癌的疗效与安全性。方法:采用紫杉醇联合DDP方案治疗ABC57例(其中含蒽环类耐药性乳腺癌26例)。紫杉醇175mg/m2,静脉滴入,d1(或分为d1、d8);DDP70mg/m2,静脉滴入,d1(或分为d1～d3),加水化、利尿和止吐治疗,21d为1个周期。本组中位化疗周期数为3个。结果:完全缓解6例,部分缓解24例,稳定16例,疾病进展11例,总的有效率52.6%(30/57),26例蒽环类耐药性乳腺癌患者的有效率为61.5%(16/26)。治疗时一般情况较好者疗效(53.5%)好于一般情况差者(23.3%),P=0.045。中位肿瘤进展时间7个月,1年生存率为61.4%,中位生存期为19个月。主要毒性反应为骨髓抑制及胃肠道反应。结论:紫杉醇和DDP联合方案治疗ABC,特别是蒽环类耐药性乳腺癌疗效较好,使用方便,毒性反应较轻。该方案是包括蒽环类耐药性ABC的有效解救治疗方案。

Herceptin治疗Her-2过度表达的转移性乳腺癌7例报告

为探讨抗Her-2受体单克隆抗体Herceptin对Her-2阳性的转移性乳腺癌的治疗作用,观察了7例接受Herceptin联合TAX或NVB治疗的Her-2/neu阳性的转移性乳腺癌患者的疗效和毒副反应。结果7例中完全缓解（CR）2例,部分缓解（PR）3例,稳定（SD）1例,进展（PD）1例,有效率为71.4％（CR+PR）,且未发现有任何与Herceptin有关的毒副反应出现。初步分析近期缓解率与Her-2/neu表达状况明显相关。

卡培他滨联合多西紫杉醇治疗转移性乳腺癌的临床观察

为了探讨卡培他滨和多西紫杉醇联合方案治疗转移性乳腺癌的疗效及不良反应，29例转移性乳腺癌患者接受卡培他滨和多西紫杉联合方案化疗。卡培他滨2．0g／m^2，d1～d14；多西紫杉醇35mg／m^2，d1、d8、d15。21d重复，化疗2个周期以上。结果示29例患者入选，2例出组，27例可供评价疗效，29例可评价不良反应。有效率为51．9％（14／27），获益率为88．9％（24／27）；主要不良反应为手足综合征、皮肤色素沉着、白细胞减少、血小板减少、血红蛋白降低、恶心呕吐、口腔炎、腹泻、肝功能损害、脱发、心脏毒性、末梢神经毒性、过敏反应等。初步研究结果提示，对蒽环类药物和（或）紫杉醇治疗失败的转移性乳腺癌，卡培他滨联合多西紫杉醇是一种新的选择方案。

吉西他滨联合卡培他滨治疗耐药转移性乳腺癌56例临床分析

为了评估吉西他滨(GEM)和卡培他滨(CAP)3周联合化疗方案在蒽环类和(或)紫杉类耐药的转移性乳腺癌(MBC)患者中的有效性和毒性,对56例既往用过蒽环类和紫杉类的MBC患者给予GEM1000mg/m2,静脉滴入30min,d1、d8;CAP2000mg/m2,分2次口服,d1～d14,每3周为1个周期。所有患者均评估毒性,至少用过2个周期的患者评估疗效。结果:56例患者共完成196个周期化疗,中位化疗周期数为3.5个周期。完全缓解4例,部分缓解22例,稳定18例,进展12例,有效率为46.4%(26/56)。最常见的毒副反应为骨髓抑制和手足综合征。初步研究结果提示,GEM和CAP联合化疗方案在既往接受过蒽环类和紫杉类药物的MBC患者中是安全有效的,血液学和非血液学毒性都可耐受。

重组人血管内皮抑制素联合全身化疗治疗转移性乳腺癌的临床疗效观察

目的评价重组人血管内皮抑制素联合全身化疗治疗转移性乳腺癌的有效性和安全性。方法 14例转移性乳腺癌患者均接受重组人血管内皮抑制素联合全身化疗方案的治疗。重组人血管内皮抑制素7.5mg/m2,加入500mL生理盐水中,静脉滴注3～4h,连续用药14d,间歇7d重复。化疗方案则根据患者既往治疗方案选用可能有效的化疗方案,按照RECIST 1.1标准评价疗效及NCI-CTC 3.0评价毒性。结果 14例患者均为女性,其中11例患者可评价疗效,6例PR,3例疾病稳定(SD),2例疾病进展(PD),客观缓解率为54.5%(6/11),疾病控制率为81.8%(9/11),无疾病进展生存时间(PFS)为3～35个月,中位PFS为6个月。主要不良反应有中性粒细胞减少、贫血、血小板减少、脱发、乏力、恶心呕吐。此外阴道流血1例,尿路及肺部感染各1例,各种不良反应经对症处理均可恢复,未发现心脏、肝脏及肾脏等器官的功能损害。结论重组人血管内皮抑制素联合全身化疗治疗转移性乳腺癌疗效肯定,不良反应可耐受,安全性高。

卡培他滨联合多西紫杉醇治疗蒽环类耐药的转移性乳腺癌31例

为了探讨卡培他滨联合多西紫杉醇（DTX）治疗蒽环类耐药的转移性乳腺癌的疗效及不良反应，将61例确诊蒽环类耐药的转移性乳腺癌分为两组，联合组31例卡培他滨1650mg／（m^2·d），口服，d1～d14，DTX75mg／（m^2·d），静脉滴入，d1。时照组30例DTX 100mg／（m^2·d），静脉滴入，d1。两组每3周为1个周期，连用4个周期，治疗结束2周后评价疗效。61例均可评价疗效，联合组有效率（CR＋PR）为45．2％（14／31），中位生存时间为14．3个月。Ⅱ～Ⅲ度反应占67．7％（21／31），Ⅳ度反应占29．0％（9／31），主要为手足综合征、骨谴抑制、脱发和消化道毒性。时照组有效率（CR＋PR）为30．0％（9／30），中位生存时间为10．9个月。Ⅱ～Ⅲ度反应占50．0％（15／30）。Ⅳ度反应占33．3％（10／30），主要为发热、肌痛、关节痛、嗜中性粒细胞减少症。初步研究结果提示，卡培他滨联合DTX时经吡柔比星治疗失败的乳腺癌较DTX’单药有优势，且不良反应可以耐受。

吉西他滨联合顺铂二、三线治疗晚期三阴乳腺癌临床观察

目的观察吉西他滨／顺铂21天方案（GP方案），二、三线治疗转移性三阴乳腺癌（advanced triplenegative breastcancer，ATNBC）患者的疗效和不良反应。方法34例三阴乳腺癌患者，吉西他滨1．0g／In。第1、8天静脉滴注；顺铂25mg／m2。第1—3天静脉滴注，21天为一疗程，直到疾病进展或无法耐受或最多接受6周期化疗。结果34例患者共完成141个周期化疗，中位化疗周期3．5周期。均可评价疗效和不良反应。其中完全缓解0例（0％），部分缓解11例（32．35％），稳定9例（26．44％），进展14例（41．18％）。有效率（CR＋PR）32．4％（95％可信区间24．15％-40．55％），疾病控制率（CR＋PR＋SD）58．8％，中位疾病进展时间（TTP）3．9月，中位生存期（OS）10.0月。治疗后主要不良反应为血液学毒性，血小板减少发生率为61．8％。结论三阴性乳腺癌预后差，GP方案治疗ATNBC患者安全有效，不良反应可以耐受。

长春瑞滨联合吉西他滨治疗蒽环类和紫杉类药物耐药的转移性乳腺癌的临床疗效分析

目的:观察长春瑞滨(vinorelbine,NVB)联合吉西他滨(gemcitabine,GEM)治疗蒽环类和紫杉类药物耐药的转移性乳腺癌(anthracycline-and taxane-refractory metastatic breast cancer,ATRMBC)患者的疗效和不良反应。方法:采用NVB联合GEM方案(GN方案)治疗41例ATRMBC患者,NVB25mg/m2静脉推注,第1、8天;GEM1000mg/m2静脉滴注,第1、8天;21d为1个周期,最多接受6个周期的化疗。结果:41例患者共完成159个周期的化疗,中位化疗周期为4个周期。完全缓解1例(2.4%),部分缓解14例(34.2%),稳定18例(43.9%),进展8例(19.5%);客观有效率36.6%(95%CI:21.9～51.3);平均随访16.4个月,中位疾病进展时间6.1个月,中位生存期16.2个月。结论:NVB联合GEM是治疗ATRMBC的有效方案,患者对不良反应能够耐受。