Decrease in the Ki67 index during neoadjuvant chemotherapy predicts favorable relapse-free survival in patients with locally advanced breast cancer

Objective: The purpose of this study was to explore the optimal cutoffs of the three parameters of Ki67 during NAC for predicting patient prognosis and investigate whether the optimal cutoffs of the Ki67 values were associated with relapse-free survival(RFS) or breast cancer-specific survival(BCSS).Methods: A total of 92 patients with locally advanced breast cancer(LABC), who had residual disease after NAC were retrospectively investigated.The optimal cutoff values of the Ki67 parameters were assessed by the online algorithm Cutoff Finder.Kaplan-Meier analysis, the log-rank test and Cox regression analysis were carried out to analyze survival.Results: The optimal cutoff values for the postsurgical Ki67 level and the decrease in the Ki67 level during NAC were defined as 25% and 12.5%, respectively.According to the univariate survival analysis, a higher Ki67 level in residual disease was associated with poor RFS(P = 0.004) and BCSS(P = 0.014).In addition, a Ki67 expression decrease > 12.5% during NAC was related to favorable RFS(P = 0.007), but was not related to BCSS(P = 0.452).Cox regression analysis showed that the Ki67 expression decrease(> 12.5% vs.≤ 12.5%) and histological grade(grade 3 vs.grade 1-2) were the independent factors associated with RFS(P =0.020 and P = 0.023, respectively), with HR values of 0.353(95% CI: 0.147-0.850) and 3.422(95% CI: 1.188-9.858), respectively.Conclusions: The Ki67 decrease was one of the independent factors associated with RFS in LABC patients with residual disease after receiving NAC.

Oncoplastic Breast Surgery after Neoadjuvant Chemotherapy Replacing Mastectomy in Locally Advanced Breast Cancer (LABC): Single Institute Experience

Background: Integration of neoadjuvant chemotherapy (NCT) in early 70s resulted that many LABC tumors become resectable but with total mastectomy especially those with partial response, oncoplastic techniques give better oncological outcome with better cosmetic results. Objective: We evaluate the oncological safety of oncoplastic breast surgery (OS) in LABC showing partial response to NCT. Methods: We prospectively analyzed the data of 32 out of 58 patients with LABC who showed partial response to NCT and could have conservative surgery with advanced oncoplastic techniques rather than total mastectomy. Results: Out of 58 patients with LABC, received neoadjuvant chemotherapy, complete response was observed in 8 patients (13%), partial response reported in 32 (55.1%) cases, 12 patients (20%) had stable disease and 6 patients (10%) showed progressive disease. Data of 32 cases were studied (mean age 44.84 ± 9.10 years;range 26 - 59 years). Inferior pedicle was performed in 9 cases, mini LD flap in 3 patients, 5 had Grissotti technique, 6 with superomedial pedicle, 4 had V mammoplasty and 3 with J mammoplasty and 2 had vertical mammoplasty. Margins were positive in 5 cases (15.6%) with mean margin width 9.63 ± 5.72 (range 0 - 22 mm), and the local recurrence was reported in 2 cases (6.2%). Complications were reported in 3 cases (9.3%). The follow up was 1.67 ± 1.03 (range 0 - 3.3 years). Conclusions: Integration of neoadjuvant chemotherapy together with advanced oncoplastic techniques opens a new way for management of LABC especially those showing partial response with avoidance of total mastectomy, and comparable oncological safety in addition to better aesthetic and psychological outcome.

Evaluation of dynamic contrast-enhanced MRI in monitoring early response of locally advanced breast cancer to neoadjuvant chemotherapy

Objective： The aim of our study was to assess the value of dynamic contrast-enhanced magnetic resonance imaging （DMRI） in predicting early response to neoadjuvant chemotherapy （NAC） in patients with locally advanced breast cancer （LABC） and to assess the accuracy of DMRI in evaluating residual disease after NAC. Methods： DMRI were per- formed in 43 women with LABC （44 lesions, all were invasive ductal carcinoma） before, after the first and final cycle of NAC. Tumour volume, early enhanced ratio （El）, maximum enhanced ratio （Emax）, and maximum enhanced time （Tmax）, dynamic signal intensity-time curve were obtained during treatment. Residual tumour volumes obtained using DMRI were compared with pathological findings to assess the accuracy of DMRI. Results： After 1st cycle of NAC, the mean volume of responders decreased insignificantly, P 〉 0.05, but after NAC, mean volume of residual tumor decreased significantly （P 〈 0.01）. Morphol- ogy change： 29 cases showed a concentric shrinkage pattern while 7 cases showed a dendritic shrinkage pattern. Significant differences were found in El, Emax and Tmax between responders and non-responders （P 〈 0.05）. After 1st cycle of NAC, El, Emax and Tmax of responders changed significantly （P 〈 0.001）; while there is no significant change in non-responders （P 〉 0.05）. After NAC, dynamic signal intensity-time types were changed in responders, and tended to be significantly flat- tening, while no significant change was found in non-responders. The residual tumour volume correlation coefficient between DMRI and pathology measurements was very high （r = 0.866, P = 0.000）. Conclusion： DMRI is useful to evaluate the early response to NAC in LABC. The presence and volume of residual disease in LABC patients treated with NAC could be ac- curately evaluated by DMRI.

Evaluation of the effect of neoadjuvant chemotherapy on tumor and axillary lymph nodes in locally advanced breast cancer: a study of 50 patients

Objective： The purpose of the study was to correlate between effect of pre-neoadjuvant chemotherapy （NACT） and post-NACT clinical, sonographic and pathologic features of the tumor and axillary lymph nodes （ALNs） and to raise the possibility of applying the concept of sentinel lymph node biopsy （SLNB） in patients with initially positive ALNs before NACT. Methods： A prospective study of 50 female patients with locally advanced breast cancer （LABC） with clinically palpable.and cytologically （under ultrasonographic guidance） positive ALNs. All patients received NACT and then referred for ultrasono- graphic assessment of the axilla regarding any detectable sonographic criteria of metastatic deposits in ALNs as well as the tumor size in relation to its prechemotherapy size, All patients were then subjected either to modified radical mastectomy or breast conserving surgery. The clinical, sonographic and pathological response of the tumor and the ALNs were documented, classified and correlated with each other. Results： Patients＇ mean age was 47.7±9.1 years. The mean clinical tumor size was 6.7 ± 1.4 cm; stage IliA that was presented in 32 patients （64%） and IIIB was presented in 18 patients （36%）. Chemotherapy was given for a median of 4 cycles, there was reduction of the mean clinical tumor size from 6.7 ± 1.4 cm to 4.3 ± 2.7 cm （P 〈 0.001）. Clinical response was complete in 5 （10%） tumors, complete pathological tumor response （post-neoadjuvant） was detected in 6 （16%） of patients. Complete clinical nodal response （post-neoadjuvant） in 23 （46%） axillae, on sonographic assessment of the axilla, response was complete in 17 （34%） axillae. Complete pathological nodal response occurred in 16 （32%） axillae. Out of 17 axillae that showed complete sonographic response 11 axillae showed complete pathological nodal response （P 〈 0.001）. Conclusion： Formal axillary lymph node dissection can be avoided and replaced by SLNB post NACT in patients with LABC with metastatic ALNs if there were complete clinical and sonographic criteria of nodal response as well as complete pathological tumor response.

Weekly taxane-anthracycline combination regimen versus tri-weekly anthracycline-based regimen for the treatment of locally advanced breast cancer:a randomized controlled trial

Background:Extensive studies have confirmed the efficacy of taxanes in combination with anthracycline-based chemotherapy on breast cancer.However,few studies have assessed the efficacy of weekly taxane-anthracycline regimens on locally advanced breast cancer.This study was to compare the efficacy and safety of a weekly taxaneanthracycline regimen with those of tri-weekly anthracycline-based regimen in patients with locally advanced breast cancer.Methods:Patients with locally advanced breast cancer were randomized to receive 4-6 cycles of neoadjuvant chemotherapy with tri-weekly 5-fluorouracil-epirubicin-cyclophosphamide(FEC) regimen or weekly paclitaxel-epirubicin(PE) regimen.The primary endpoint was the pathologic complete response(pCR) rate.Other endpoints included the clinical tumor response,breast-conserving surgery rate,and adverse events.Results:Between March 2010 and September 2013,293 patients were randomized to the FEC(n=151) and PE(n=142) arms.The overall clinical response rate was significantly higher in the PE arm than in the FEC arm(76.06%vs.59.95%,P=0.001).Consistently,the post-chemotherapy pathologic T and N stages were significantly lower in the PE arm than in the FEC arm(P<0.001).However,the pCR rate was similar in the two arms(10.61%vs.12.31%,P=0.665).Overall,36(27.27%) patients in the FEC arm and 6(35.28%) in the PE arm were qualified for breast-conserving surgery.Most adverse events were comparable in both arms,with more severe neutropenia in the PE arm than in the FEC arm(11.97%vs.5.96%,P=0.031).Conclusions:In patients with locally advanced breast cancer,weekly PE was not superior to FEC in terms of pCR.However,weekly PE has a higher response rate and superior down-staging effects.On this account,the PE regimen may be considered an alternative option for locally advanced breast cancer.Long-term follow-up data are needed to confirm the efficacy of this regimen on locally advanced breast cancer.Trial registration Chinese clinical trial registry,ChiCTR-TRC-10001043,September 21。

背阔肌肌皮瓣在新辅助化疗后cT4局部晚期乳腺癌创面修复中的应用

目的:探讨背阔肌肌皮瓣(LDMF)在新辅助化疗(NAC)后cT4局部晚期乳腺癌(cT4-LABC)创面修复中的应用效果。方法:回顾性分析2017年12月至2020年08月间我科收治14例cT4-LABC患者,在经过抗感染和NAC达到临床获益(PR+SD)后,局部行乳腺癌根治性切除术,并即刻应用LDMF修复胸壁缺损。结果:14例患者中13例(13/14,92.9%)完成既定周期的NAC,1例仅完成2周期NAC(剔除研究)。在纳入研究的13例患者中,无CR和PD病例,PR 12例(12/13,92.31%),SD 1例(1/13,7.69%),NAC临床获益率100%(13/13)。13例患者均成功完成手术,手术时间4~6小时,术中出血200~300 mL,术后2例皮肤缺血坏死(2/13,15.38%),通过换药自行愈合,拔管后8例供区出现少量血清肿(8/13,61.54%),通过抽液、加压包扎处理后消失。随访1~36个月,中位随访22个月,1例局部复发(1/13,7.69%)、3例远处转移(3/13,23.08%)、2例死亡(2/13,15.38%),所有患者背阔肌功能良好,上肢活动基本正常。结论:cT4-LABC在保证全身治疗有效后,局部手术时应用LDMF即刻修复胸壁缺损切实可行,效果确切,值得推广。

去甲长春花碱加表柔比星新辅助化疗方案治疗局部晚期乳腺癌的临床研究

目的:了解诺维本加表柔比星(表阿霉素)的联合新辅助化疗方案在局部晚期乳腺癌治疗中的疗效和毒性反应。方法:2001年9月～2003年2月,76例Ⅱb期至Ⅲb期的局部晚期乳腺癌病人入组本次临床试验。入组病例术前接受的新辅助化疗方案为:诺维本25 mg/m2,第1、8天;表阿霉素60 mg/m2,第1天,每三周为1个疗程,共3个疗程。分别观察新辅助化疗后肿瘤原发病灶和区域淋巴结的缓解情况,并观察新辅助化疗的毒性反应。结果:原发病灶临床有效率为84.2％,其中完全缓解(CR)19.7％,部分缓解(PR)64.5％,疾病稳定(SD)14.5％,疾病进展(PD)1.3％;病理完全缓解率为14.5％(11/76)。32例化疗前细针穿刺活检明确区域淋巴结转移阳性的病人中,9例(28.1％)术后病理腋淋巴结转移阴性。毒性反应主要为白细胞减少症、脱发和恶心/呕吐,共有39例(54.2％)病人发生了Ⅲ到Ⅳ度的白细胞减少症,但未有因此而发生的败血症和死亡病例。结论:诺维本加表阿霉素的新辅助化疗方案在局部晚期乳腺癌的治疗中疗效显著,耐受性良好。

局部晚期乳腺癌的治疗进展

新辅助化疗后再手术和(或)放疗已成为治疗局部晚期乳腺癌的治疗模式。本文综述新辅助化疗的依据、疗程方案、影响疗效及预后相关因素及其优缺点,同时介绍了局部晚期乳腺癌诊断,局部治疗及内分泌治疗等方面的进展。

TAC与AT方案新辅助化疗治疗局部晚期乳腺癌疗效分析

目的:观察多西他赛、吡柔比星联合环磷酰胺方案(TAC)与多西他赛联合吡柔比星方案(AT)新辅助化疗治疗局部晚期乳腺癌近期疗效和毒副反应。方法:回顾性分析72例局部晚期乳腺癌新辅助化疗患者资料,TAC组(38例)为观察组,AT组(34例)为对照组,每周期化疗前行疗效评估及毒副反应分析,第4周期化疗结束后总体评价疗效。结果:观察组治疗局部晚期乳腺癌总有效率为89.47%,对照组为70.59%,观察组优于对照组,差异有统计学意义(P<0.05);化疗毒副反应严重程度观察组较对照组重,两组之间差异无统计学意义(P>0.05)。结论:TAC与AT方案新辅助化疗治疗局部晚期乳腺癌均有较好疗效,TAC方案优于AT方案。

局部进展期乳腺癌新辅助化疗前后生物标志物表达变化与疗效的相关性

目的:探讨局部进展期乳腺癌行新辅助化疗前后相关生物标志物的表达变化情况与化疗疗效的相关性。方法:采用免疫组化方法检测102例新辅助化疗前后局部进展期乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体-2(HER-2)、p53和增殖细胞核抗原(Ki-67)等表达,分析化疗前后生物标志物表达变化与化疗疗效的相关性。结果:ER阴性组、PR阴性组、Ki-67高表达组的新辅助化疗有效率分别为50.0%、49.1%、51.4%,高于ER阳性组26.0%、PR阳性组25.5%、Ki-67低表达组9.4%(P<0.05)。Logistic多因素回归分析显示,ER、Ki-67的表达水平是评估化疗疗效的独立因素(P<0.05)。Luminal型乳腺癌总生存期高于non-Luminal型(Long-rank检验,P<0.05)。结论:ER、Ki-67、分子亚型可作为局部进展期乳腺癌新辅助化疗疗效判断的重要预测指标。

局部晚期乳腺癌新辅助化疗每周方案与三周方案疗效分析

目的探讨比较局部晚期乳腺癌采用剂量密集法和非剂量密集法行新辅助化疗的近期疗效。方法45例ⅢA期乳腺癌患者随机进入密集化疗组(A组)和非密集化疗组(B组)。A组:紫杉醇70mg/m2,表阿霉素30mg/m2,每周1次,连用3周,4周为1个周期。B组:紫杉醇135mg/m2,第1天,表阿霉素80mg/m2,第1天,3周为1个周期。如无疾病进展,共治疗3个周期。结果A组获CR7例(31.82%),PR12例(54.54%),SD3例(13.64%),pCR5例(22.73%),有效率(RR)为86.36%。B组获CR6例(26.09%),PR11例(50%),SD6例(26.09%),pCR3例(13.04%),RR为73.91%。A组的RR、CR、pCR均优于B组,但无统计学意义。进一步分层分析,不同基因型乳腺癌新辅助化疗的疗效相当,无论A组或B组,其IuminalB型、Basal-like型和HER-2阳性型三者之间新辅助化疗的RR、cCR、PR、pCR的差别无统计学意义。两组3～4级毒副反应发生率除中性粒细胞减少外均相近。两组随访期间全部存活,OS正在进一步随访中。结论紫杉类每周方案与标准的三周方案相比,可作用于不同增殖动力学的肿瘤细胞,剂量密度增加,更易于与其他化疗药物配伍,且每周方案较三周方案有更高的疗效,急性毒性无明显增加。

新辅助化疗对局部进展期乳腺癌患者T淋巴细胞亚群及NK细胞免疫功能的影响

目的:探讨局部进展期乳腺癌患者新辅助化疗前、后T淋巴细胞亚群及NK细胞免疫功能的变化。方法:采用流式细胞术检测54例局部进展期乳腺癌患者新辅助化疗前后的静脉血T淋巴细胞亚群及NK细胞免疫功能。美国癌症联合会(American Joint Commitree on Cancer,AJCC)肿瘤分期为Ⅱb期(仅T3N0M0)和Ⅲ期(不包括N3),静脉血于第1周期新辅助化疗治疗前及第3周期化疗后21日抽取,淋巴细胞亚群检测包括:T(CD3+,CD4+,CD8+),NK(CD56+,CD16+),经过3周期新辅助化疗CEF方案(表柔比星、环磷酰胺和5-氟尿嘧啶),根据新辅助化疗临床效果评价分为2组,化疗有效组38例(CR和PR),化疗无效组16例(SD和PD),并与正常体检健康者(40例)作比较。结果:乳腺癌患者治疗前CD4+、CD4+/CD8+明显低于对照组(P<0.01),NK细胞明显低于对照组(P<0.05),新辅助化疗后,有效组总CD3+、CD4+、CD4+/CD8+、NK细胞较治疗前均显著升高(P<0.05),CD8+降低(P<0.05);无效组CD3+、CD4+/CD8+及NK细胞较治疗前显著降低(P<0.05),而CD8+升高(P<0.05)。结论:局部进展期乳腺癌患者免疫功能低下,有效的辅助化疗能提高患者的免疫功能,定期监测免疫功能对指导临床治疗有意义。

氢质子磁共振波谱监测乳腺癌新辅助化疗疗效的应用研究

目的:探讨乳腺癌氢质子磁共振波谱(1H-MRS)的谱线特征及早期监测乳腺癌新辅助化疗疗效的价值。方法:前瞻性研究一组98例在术前进行新辅助化疗的乳腺癌患者(99个病灶,98个浸润性导管癌,1个黏液腺癌),比较按疗程随访的1H-MRS结果(化疗前,一疗程后),观察分析胆碱共振峰的峰高、峰下面积及胆碱信噪比,以评估新辅助化疗疗效。所有病例均经手术病理证实。结果:①1H-MRS可用于乳腺癌监测(成功率83.8%),乳腺癌可出现明显的胆碱复合峰,敏感度75.9%(63/83)。②48个成功随访病灶中,8个治疗无效,40个有效;③比较治疗有效、无效组Cho峰高、峰下面积及信噪比,P<0.05,差异有统计学意义。④治疗有效组一疗程后Cho峰高、峰下面积及信噪比的变化有显著统计学意义,P<0.001,肿瘤Cho峰有下降趋势或部分消失;无效组Cho峰变化无统计学意义(P>0.05)。结论:1H-MRS可用于乳腺癌的诊断,并可在乳腺癌新辅助化疗早期通过Cho的变化,评价、预测新辅助化疗疗效,提供早期判断疗效的有价值信息。

不同新辅助化疗方案治疗局部晚期乳腺癌的疗效比较

目的探讨新辅助化疗不同的治疗方案对局部晚期乳腺癌的患者的疗效。方法72例接受新辅助化疗的乳腺癌(ⅢA期)患者随机分为3组:即TA组(n=24)(紫杉醇联合吡柔比星):TXL 135 mg/m2静滴,d1,THP 40 mg/m2静推,d2。CAF组(n=24)(吡柔比星联合环磷酰胺,5-氟尿嘧啶):THP 40 mg/m2静推,d1,CTX 600 mg/m2,静推,d1.8,5-FU 12 mg/kg,d1-5,静滴。CMF组(n=24)(环磷酰胺联合5-氟尿嘧啶,氨甲喋呤):CTX 600 mg/m2静推d1.8,5-FU 12 mg/kg,静滴,d1-5,MTX 0.4 mg/kg,d1,静推。21 d为一个周期,2个周期后对乳腺癌原发病灶及腋窝淋巴结状态进行观察及分析。结果TA组总有效率为83%,CAF组总有效率为63%,CMF组总有效率25%。TA组与CMF组相比较有显著差异(P<0.05),CAF组与CMF组相比较有显著差异(P<0.05),TA组与CAF组相比较无统计学意义(t=0.022,P>0.05)。结论TA组和CAF组在局部晚期的乳腺癌新辅助治疗的过程中疗效满意,毒副反应可以耐受,值得推广。

磁共振扩散加权成像ADC值对局部进展期乳腺癌新辅助化疗疗效及病理反应性的评估价值

目的探讨磁共振扩散加权成像(DWI)的表观扩散系数(ADC)值对局部进展期乳腺癌新辅助化疗(NAC)疗效及病理反应性的评估价值。方法对108例局部进展期乳腺癌患者术前进行4个周期的NAC治疗,分别于化疗前、化疗结束后进行DWI检查,测量病灶ADC值;根据临床疗效及病理反应性分级分为完全缓解(CR)+部分缓解(PR)组和疾病稳定(SD)+疾病进展(PD)组;组织学显著反应(MHR)组和组织学非显著反应(NMHR)组,比较两组间ADC值变化及与病理反应性结果的相关性。结果化疗后,CR+PR组的ADC值明显升高,且显著高于SD+PD组(P<0.05);化疗后的肿瘤体积变化与化疗前ADC值呈显著负相关,与ΔADC呈显著正相关(r=-0.463,0.539,P<0.05);化疗后,MHR组和NMHR组患者的ADC值均明显升高,但MHR组ADC值、ΔADC均显著高于NMHR组(P<0.05)。结论 DWI的ADC值对局部进展期乳腺癌NAC化疗早期疗效及病理反应改变具有较好的评估价值。

薏苡仁提取物联合新辅助化疗对局部晚期乳腺癌组织Survivin及Ki-67表达的影响

[目的]探讨薏苡仁提取物康莱特(KLT)联合新辅助化疗对局部晚期乳腺癌(locally advanced breast cancer,LABC)患者乳腺癌组织Survivin和Ki-67表达的影响及意义。[方法]选择2011年1月至2013年10月在我院就诊并确诊为LABC的患者90例,随机分为化疗组(Che组)及KLT联合化疗组(Che+KLT组)各45例,治疗3个疗程后比较两组的肿瘤缓解率,并应用免疫组化SABC法检测两组患者治疗前后组织中Survivin和Ki-67的表达水平,采用统计学方法对两组数据进行分析比较。[结果]两组患者比较,Che组的缓解率为71.1%,Che+KLT组的缓解率为86.7%,两组比较差异具有统计学意义(P<0.05)。尤其是PCR率,Che+KLT组为28.9%,较Che组的17.8%差异更为明显,且有统计学意义(P<0.01)。Survivin表达率Che组由治疗前的68.9%下降到48.9%,Che+KLT组由治疗前的66.7%下降到33.3%,两组治疗前后比较差异均有统计学意义(P<0.05);Ki-67阳性表达率Che组由治疗前的80.0%下降到53.3%,Che+KLT组由治疗前的73.3%下降到40.0%,两组治疗前后比较差异均有统计学意义(P<0.05)。治疗后Che+KLT组Survivin、Ki-67的表达率与Che组比较差异均有统计学意义(P<0.05)。[结论]KLT可能通过协同新辅助化疗下调乳腺癌患者Survivin和Ki-67表达而抑制肿瘤细胞,提高肿瘤缓解率。

多西他赛、环磷酰胺与多西他赛、吡柔比星新辅助化疗方案治疗局部晚期乳腺癌疗效分析

目的观察多西他赛、环磷酰胺（DC方案）与多西他赛、吡柔比星（DT方案）新辅助化疗方案治疗局部晚期乳腺癌的临床疗效和不良反应。方法经麦默通穿刺确诊局部晚期乳腺癌可手术患者73例，随机分为DC组（35例），DT组（38例），分别给予DC方案，DT方案化疗3个周期，DC组35例，DT组38例化疗结束2周后行乳腺癌改良根治术。比较DC组，DT组疗效和不良反应，治疗前、后TNM分变化、术后并发症及化疗前后ER、PR、HER2变化比较。结果临床疗效比较DT组优于DC组，其差异有统计学意义（P〈0．05）；TNM分期均较新辅助化疗前降低（P〈0．05），不良反应比较差异无统计学意义（P〉0．05）；术后并发症比较差异无统计学意义（P〉0．05），ER、PR均为阴性患者对化疗敏感，DT方案对于HER2高表达患者疗更敏感。结论DT及DC新辅助化疗方案疗对局部晚期乳腺癌均有效，DT方案优于DC方案。

Luminal B型局部晚期乳腺癌新辅助化疗疗效预测基因的研究

目的筛选Luminal B型局部晚期乳腺癌新辅助化疗疗效预测基因。方法收集10例Luminal B型乳腺癌患者,均行DA方案新辅助化疗(多西他赛75mg/m2静滴,d1;表阿霉素80mg/m2静滴d1,21天为1周期,共4个周期),根据化疗疗效分为完全病理缓解(pCR)组(n=3)和非完全病理缓解(npCR)组(n=7)。采用人基因表达谱cDNA芯片从10例乳腺癌患者中筛选新辅助化疗疗效相关基因,荧光定量PCR验证差异表达基因。结果 pCR组与npCR组癌组织相比,上调基因231个,下调基因195个;pCR组癌组织与癌旁组织相比,上调的基因357个,下调的基因544个;npCR组癌组织与癌旁组织相比,上调基因143个,下调基因101个;pCR组与npCR组癌旁组织比较,上调基因98个,下调基因67个。pCR组与npCR组癌组织比较,筛选出6个与肿瘤有关的基因,其中上调基因为CYP4Z1、FGFL6、BCAR4,下调基因为FABP4、S100B、ALPH1L1。荧光定量PCR进一步验证显示,两组mRNA表达差异的基因为CYP4Z1和BCAR4,pCR组两种基因表达均显著低于npCR组(P<0.05)。结论对局部晚期Luminal B型乳腺癌低表达BCAR4和CYP4Z1的患者新辅助治疗选择采用DA方案化疗更有可能获得pCR。

局部晚期乳腺癌经内乳动脉置管新辅助化疗47例临床研究

目的 探讨内乳动脉置管给药新辅助化疗对局部晚期乳腺癌的临床疗效及安全性。方法 选择不宜一期手术、临床分期Ⅲa-Ⅲc期的局部晚期乳腺癌患者92例为研究对象,随机分为研究组（n=47）和对照组（n=45）,研究组采取患侧内乳动脉置管、微量泵给药,对照组采取周围静脉给药,进行新辅助化疗,化疗方案为FEC方案：环磷酰胺500 mg/m^2,D1;表柔比星100 mg/m^2,D1;氟尿嘧啶500 mg/m^2,D1、4。21 d为1个周期。2-4个周期后视情况行乳腺癌根治术。术后对两组新辅助化疗疗效、毒性反应及预后进行分级评估。结果 研究组部分缓解率和总有效率均高于对照组（P〈0.05）,经2个周期治疗即可接受手术者比例研究组明显高于对照组（P〈0.05）。2组毒性反应发生率比较差异无统计学意义（P〉0.05）。随访1年,研究组远处转移率低于对照组、无瘤生存率高于对照组（P〈0.05）。结论 与静脉给药相比,局部晚期乳腺癌经内乳动脉置管新辅助化疗效果更好,待手术时间短,且不增加药物毒性反应,是临床优选的给药途径。

吉西他滨联合长春瑞滨用于乳腺癌二线新辅助化学治疗的观察

目的:评价GN方案(吉西他滨联合长春瑞滨)作为二线新辅助化学治疗方案,用于TAC治疗方案(多西他赛、多柔比星和环磷酰胺)耐药的局部晚期乳腺癌(LABC)的疗效和安全性。方法:26例经2～4周期TAC方案化学治疗反应不佳的LABC患者,采用GN方案治疗;吉西他滨1 000 mg/m2静脉滴注,第1、8日;长春瑞滨25 mg/m2静脉滴注,第1、8日。每21日为1周期,2周期后评定疗效,同时记录不良事件。病情稳定或进展的患者停止化学治疗,缓解的患者继续行化学治疗至最多6周期,所有患者化学治疗结束2周后行手术切除。结果:26例患者共完成83周期化学治疗,平均3.2周期。其中完全缓解2例(8%),部分缓解10例(38%),病情稳定9例(35%),进展4例(15%),其中1例(4%)患者获得病理完全缓解。总反应率46%(12/26)。4例(15%)患者成功实施保乳手术,无1例患者需植皮。主要毒副反应为Ⅰ～Ⅱ度骨髓抑制、胃肠道反应、黏膜炎和周围神经毒性。结论:GN方案可作为二线新辅助化学治疗方案,用于蒽环类和紫杉类耐药的LABC患者,临床反应率较好,耐受性尚可。