乳腺癌分子分型在新辅助化疗疗效及预后预测中的作用

目的:探讨乳腺癌分子分型在新辅助化疗疗效及预后预测中的作用.方法:收集漯河市中心医院收治的236例接受新辅助化疗患者的临床病理资料,分为Luminal A、Luminal B、Her-2阳性和三阴乳腺癌4种分子分型,分析分子分型与临床病理因素、新辅助化疗疗效及 5 年生存率的相关性.结果:236例患者中,107例(45.3%)为Luminal A亚型,47例(19.9%)为Luminal B亚型,27例(11.4%)为Her-2阳性亚型,55例(23.3%)为三阴乳腺癌亚型.Her-2阳性(25.9%)及三阴乳腺癌亚型(30.9%)的病理完全缓解(pCR)率明显高于Luminal亚型(Luminal A亚型 4.7%及Luminal B亚型 8.5%),差异有统计学意义(P<0.05).与Luminal亚型相比,Her-2阳性及三阴乳腺癌亚型具有更差的5年无病生存和总生存(P<0.01);获得pCR的乳腺癌患者的5年无病生存和总生存明显高于化疗后仍有癌残留的患者(P<0.05).结论:相对于Luminal亚型,Her-2 阳性和三阴乳腺癌亚型对新辅助化疗更为敏感,更易达到pCR;但是Her-2阳性和三阴乳腺癌亚型预后反而更差.     

原发性乳腺癌分子分型与新辅助化疗疗效及预后的相关性

目的 探讨原发性乳腺癌分子分型与新辅助化疗疗效及预后之间的相关性。方法 回顾性分析河南省肿瘤医院收治的204例接受新辅助化疗患者的临床病理资料,分为Luminal A、LuminalB、HER2阳性和三阴乳腺癌4种亚型,分析乳腺癌分子分型对新辅助化疗疗效及预后的预测作用。结果 204例患者中,40例（19.6％）为Luminal A亚型,46例（22.5％）为Luminal B亚型,36例（17.6％）为HER2阳性亚型,82例（40.2％）为三阴乳腺癌亚型。HER2阳性（22.2%）及三阴乳腺癌亚型（22.4%）的病理完全缓解（pCR）率明显高于Luminal A亚型（2.5％）及Luminal B亚型（6.5％）,差异有统计学意义（P=0.03）。与Luminal亚型相比,HER2阳性及三阴乳腺癌亚型具有更差的无病生存期（DFS）（P=0.001）和OS（P=0.002）;剔除获得pCR的患者,单独评价存在肿瘤残留的患者,我们发现HER2阳性及三阴乳腺癌亚型比Luminal亚型具有更差的DFS（P<0.001）和OS（P<0.001）。获得pCR的乳腺癌患者的5年DFS和总生存期（OS）均明显高于化疗后仍有癌残留的患者（P=0.002, P=0.012）。结论 相对于Luminal亚型,HER2 阳性和三阴乳腺癌亚型对新辅助化疗更为敏感,更易达到pCR;但是HER2阳性和三阴乳腺癌亚型预后反而更差。     

乳腺癌分子分型对多西他赛联合表阿霉素新辅助化疗疗效和预后的预测价值

目的探讨乳腺癌分子分型对多西他赛+表阿霉素新辅助化疗的临床疗效及预后的预测价值。方法对126例行多西他赛+表阿霉素新辅助化疗的老年乳腺癌患者的肿瘤组织行免疫组织化学检测,依据雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体2(HER2)表达情况及Ki67水平,将乳腺癌分三阴型、HER2过表达型、Luminal A型、Luminal B型,分析不同分子分型患者病理完全缓解率(p CR)的差异,比较不同分子分型患者术后无病生存时间(DFS)和总生存时间(OS)。结果乳腺癌分子分型各组p CR依次为三阴型(42.1%)、HER2过表达型(30.8%)、Luminal A型(13.2%)和Luminal B型(4.7%),三阴型和HER2过表达型者的临床总有效率分别为94.7%和80.8%,高于Luminal A型的63.7%和Luminal B型的55.9%(P<0.05)。Cox回归分析显示,分子亚型为影响乳腺癌临床疗效的独立因素,以三阴型为对照,Luminal A型、Luminal B型的OR值分别为1.885和2.317。Luminal A型患者的OS、DFS均高于三阴型(χ~2=3.176,P=0.032;χ~2=3.743,P=0.029)。结论以ER、PR、HER2、Ki67为依据的乳腺癌分子分型可能是老年乳腺癌多西他赛+表阿霉素新辅助化疗后p CR、OS、DFS的预测指标。     

曲妥珠单抗联合新辅助化疗对HER-2阳性乳腺癌患者近远期疗效的影响

目的 探讨曲妥珠单抗联合新辅助化疗对表皮生长因子受体-2(HER-2)阳性乳腺癌患者的疗效.方法 选取HER-2阳性乳腺癌患者58例,随机分为观察组和对照组,各29例.对照组给予表柔比星联合多西他赛的方案进行新辅助化疗,观察组在对照组的基础上给予曲妥珠单抗治疗.比较两组患者的近期、远期疗效.结果 观察组有效率(RR)及病理完全缓解(pCR)率明显优于对照组,5年总生存率(OS)及5年无病生存率(DFS)明显高于对照组.结论 曲妥珠单抗联合新辅助化疗治疗HER-2阳性乳腺癌近期疗效显著,并可有效改善患者预后,值得临床推广应用.     

Ki-67与分子亚型预测乳腺癌新辅助化疗敏感性的研究

目的:探讨Ki-67表达与乳腺癌不同分子亚型预测乳腺癌新辅助化疗的敏感性.方法:收集广东省妇幼保健院乳腺中心2007-01-2011-05接受新辅助化疗的55例局部晚期乳腺癌患者的临床资料,分析Ki-67表达、乳腺癌分子亚型与新辅助化疗临床有效率及病理完全缓解之间的关系.结果:55例患者新辅助化疗后总有效率(RR)为78.2％(43/55),其中有20.0％(11/55)病例达临床完全缓解(CR),9.1％(5/55)的病例达病理完全缓解(pCR),58.2％(32/55)病例达临床部分缓解(PR),21.8％(12/55)的病例为病情稳定(SD),无患者获得疾病进展(PD).Ki-67高表达组(Ki-67≥14％)新辅助化疗临床有效率优于Ki-67低表达组(Ki-67＜14％),x2=7.004,P=0.018;但两组的肿瘤原发灶的病理完全缓解(pCR)差异无统计学意义,x2=0.008,P=1.000.在Ki-67低表达组内,不同分子亚型的乳腺癌新辅助化疗疗效,差异有统计学意义,x2 =8.306,P=0.040;三阴型乳腺癌的有效率优于Luminal A型,x2=10.617,P=0.009;三阴型、Luminal B型与HER-2过表达型的新辅助化疗有效率,差异无统计学意义,x2=5.091,P=0.078;Luminal A型、Luminal B型与HER-2过表达型的新辅助化疗有效率,差异无统计学意义,x2=0.417,P=0.812.在Ki-67高表达组内,不同分子亚型的乳腺癌新辅助化疗疗效,差异无统计学意义,x2 =2.921,P=0.404.不同分子亚型的乳腺癌新辅助化疗临床疗效,差异有统计学意义,x2=14.068,P=0.003;三阴型、Luminal B型和HER-2过表达型乳腺癌新辅助化疗的临床疗效优于Luminal A型;三阴型、Luminal B型与HER-2过表达型的新辅助化疗临床疗效差异无统计学意义,x2 =2.074,P=0.354.而这4型乳腺癌新辅助化疗的病理完全缓解(pCR)差异无统计学意义,x2=7.335,P=0.062.结论:Ki-67表达和乳腺癌分子亚型可预测新辅助化疗的疗效,Ki-67高表达和三阴型乳腺癌的患者从新辅助化疗中获益更多.     

乳腺癌分子亚型预测新辅助化疗疗效的研究

目的:探讨不同乳腺癌分子亚型对紫杉联合蒽环类的新辅助化疗方案治疗疗效的预测价值.方法:对4周期紫杉联合蒽环类新辅助化疗方案治疗182例乳腺癌的资料进行回顾性分析.用免疫组化法将乳腺癌分为四个分子亚型,了解其与临床及病理疗效的关系.结果:单因素分析发现:雌激素受体(ER)阴性、孕激素受体(PgR)阴性及分子亚型可以预测临床完全缓解(cCR)和病理完全缓解(pCR)(P值均＜0.05),HER-2过表达可以预测cCR(P＜0.05).多因素分析发现只有乳腺癌分子分型是预测cCR及pCR的独立变量(P值均＜0.05).其中Luminal B亚型、basal-like亚型、HER2+/ER-亚型对新辅助化疗方案的疗效优于Luminal A亚型(P值均＜0.05).结论:Luminal B亚型、basal-like亚型及HER2+/ER-亚型对紫杉联合蒽环类新辅助化疗方案更敏感,乳腺癌分子亚型有可能成为该方案很好的疗效预测指标.     

紫杉类联合蒽环类的新辅助化疗方案治疗三阴乳腺癌的疗效及预后

背景与目的:三阴乳腺癌(triple-negative breast cancer,TNBc)是一类不能受益于分子靶向治疗的高危乳腺癌.本研究比较紫杉类联合蒽环类新辅助化疗方案对TNBC和非TNBC的疗效及远期生存率.方法:对接受4个周期紫杉联合蒽环类新辅助化疗方案治疗的138例乳腺癌资料进行回顾性分析.用免疫组化法将雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体(Her-2)表达均阴性的肿瘤定义为TNBC,分析紫杉类联合蒽环类的新辅助化疗对TNBC和非TNBC的临床、病理疗效及其与远期生存的关系.结果:138例中37(26.8%)例为TNBC,101(73.2%)例为非TNBC.138例患者的总有效率(OR)为85.5%(118/138),其中临床完全缓解(cCR)为35.5%(49/138),临床部分缓解50.0%(69/138),病理完全缓解(pCR)30(21.7%)例.TNBC的cCR(51.4%)、pCR(45.9%)明显高于非TNBC的cCR(29.7%)、pCR(12.9%)(P<0.05).TNBC的5年无病生存率(DFS)为59.5%,低于非TNBC者(84.2%)(P=0.05);TNBC者的5年OS为75.7%,与非TNBC者(94.1%)相比差异无显著性(P=0.108).获得cCR、pCR的TNBC者的5年DFS及总生存率(OS)与非TNBC者间差异无显著性(P>0.05).相反,新辅助化疗后仍有残留病灶的TNBC的5年DFS及OS明显低于非TNBC(P<0.05). 结论:本研究结果表明,TNBC对紫杉联合蒽环类的新辅助化疗更敏感,更易获得cCR、pCR,获得cCR、pCR的TNBC患者预后好,未获得cCR、pCR的TNBC患者远期生存明显低于非TNBC.     

药物去势联合化疗在绝经前Luminal A型乳腺癌新辅助化疗中的疗效及安全性评价

背景与目的:常规新辅助化疗方案在治疗Luminal A型乳腺癌患者中达病理完全缓解(pathologic complete remission,pCR)率小于10%,寻求新型的新辅助化疗方案以提高pCR率从而进一步改善患者的预后具有重要的临床意义.我们对卡培他滨联合多西他赛(XT方案)加或不加戈舍瑞林去势在中国人群绝经前Luminal A型乳腺癌新辅助化疗的疗效及安全性方面进行了初步评价.方法:纳入研究的36例患者被随机分配至XT组或XT+去势组.两组患者术前均接受4周期XT方案新辅助化疗,XT+去势组同时接受新辅助戈舍瑞林去势治疗.主要终点为pCR率,次要终点为总体反应(overall response,0R)率.并按CTCAE v3.0对不良反应事件进行分级.采用四格表检验比较组间的pCR率与OR率的差异.结果:总共纳入36例符合入组标准的患者,按1∶1随机至XT组与XT+去势组,两组患者平均年龄分别为40.6岁(27～48岁)与42.8岁(27～48岁).所有患者均按计划完成术前4个周期新辅助治疗.XT组pCR率为16.7%,OR率为94.4%.XT+去势组pCR率为16.7%,OR率为100%.两组的pCR率与OR率均无显著差异.两组患者在新辅助化疗过程期间均未发现需要调整剂量的严重不良反应事件.结论:新辅助XT±戈舍瑞林去势在中国人群绝经前Luminal A型乳腺癌中有较高的pCR率及OR率,同时具有较高的安全性.     

局部进展期乳腺癌雌、孕激素受体和HER2的表达与双周ET新辅助化疗疗效的相关性

背景与目的:新辅助化疗(neo-adjuvant chemotherapy,NAC)在局部进展期乳腺癌(locally advanced breast cancer,LABC)中的作用已经很明确,达到病理完全缓解者可提高生存率,因而,临床上能否找到可以预测新辅助化疗效果的指标显得日益重要.对于雌、孕激素受体(ER,PR)和人类表皮生长因子受体(HER2)表达与新辅助化疗疗效之间的相关性一直存在争论,至今尚未统一.近年研究提示缩短化疗间期实施密集化疗将有希望进一步提高疗效,因此,本研究中采用表柔比星(EPI)加紫杉醇(PTX)双周ET联合方案新辅助化疗治疗LABC,同时比较ER/PR、HER2表达与疗效的相关性.方法:将82例未经治疗的Ⅱb～Ⅲb期LABC患者入组双周ET联合新辅助化疗,其方案为EPI 50 mg/m2,第1天,静脉注射;PTX 175 mg/m2,第2天,静脉滴注3 h,每2周重复1次,均接受3个周期化疗后评估,观察其疗效、不良反应以及比较ER/PR和HER2表达与疗效和预后的相关性.结果:肿瘤原发灶总有效率(RR)为85.4%,临床完全缓解(cCR)19.5%,部分缓解(PR)65.9%,病理完全缓解(pCR)12.2%.36.5%发生白细胞减少症(3～4级),3.7%出现自细胞减少性发热,心脏毒性较轻微,有4例(4.9%)发生心脏毒性(1级),1例发生心脏毒性(2级),末梢周围神经损害44.9%,主要为1～2级,所有患者完成了3个周期化疗后接受手术.ER、PR表达分别与pCR呈明显相关性(P=0.017,P=0.004),ER、PR阴性表达者pCR的概率明显大于阳性表达者.ER和PR双阴性者pCR的概率较ER和(或)PR阳性表达者有显著性增高(P=0.001).HER2过表达者pCR率为27.3%,明显高于低表达者的6.7%(P=0.020).结合分子亚型比较,三阴性组和HER2过表达组pCR明显高于Luminal A和Luminal B.获得pCR患者中,HER2过表达和无表达者的5年无病生存率(DFS)和总生存率(OS)差异无统计学意义,相反,在非pCR患者中,HER2过表达者DFS、OS却明显低于HER2无表达者.结论:双周ET联合方案在LABC的新辅助化疗中疗效显著,耐受性良好,ER、PR和HER状态能较好预测pCR,HER2过表达者提高了获得pCR患者的生存率,而未获得pCR的患者预后更差.     

新辅助化疗用于可手术乳腺癌的10年疗效

目的：探讨新辅助化疗对可手术的乳腺癌10年疗效。方法：可手术的乳腺癌（Ⅱ、Ⅲ期）510例，分两组治疗：新辅助化疗组（A组）251例；术后辅助化疗组（B组）259例。A组术前短程密集联合化疗，每周1次连用4次，休2周行根治性手术。两组患者术后2周内开始化疗，化疗方案和完成化疗周期相同。结果：A组Ⅲ期患者5年生存率（OS）59．2％，无瘤生存率（DFS）54．9％，均高于B组（28．3％和20．8％）（P＜0．05）。A组Ⅱ期患者10年OS78．1％，DFS73．5％，均高于B组（OS 68．4％，DFS 60．7％）（P＜0．05）。A组Ⅲ期患者10年OS 42．3％，DFS 40．4％，也高于B组（OS20．4％，DFS 18．4％）（P＜0．05）。结论：新辅助化疗可提高Ⅱ、Ⅲ期可手术乳腺癌患者的10年生存率。     

乳腺浸润性导管癌分子分型与临床特征的关系

目的探讨乳腺浸润性导管癌不同分子亚型的分布,并分析各分子亚型与临床特征的关系。方法收集2006年1月-2011年6月明确诊断为乳腺浸润性导管癌病例100例,根据雌激素受体（ER）、孕激素受体（PR）、表皮生长因子受体-2（HER-2）的表达情况划分为四型,进一步分析不同分子亚型与浸润性导管癌临床特征的关系。结果100例中Luminal A型所占比例最大为65%,7%为Luminal B型, Triple Negative型占17%,Her-2(+)型占11%。各分子亚型乳腺浸润性导管癌患者发病年龄主要集中在40~59岁之间,占73%,Luminal A型发病年龄主要集中在40~49岁,而其他三型主要分布于50~59岁,四型在不同年龄组的分布上差异有统计学意义（P＜0.05）;Luminal A型淋巴转移发生率仅为30.1%,而Luminal B型与Her-2(+)型淋巴转移发生率较高,分别为71.4%及63.6%,各分子亚型的腋窝淋巴结转移率有显著差异（P＜0.05）;病理组织学分级Ⅰ级中Luminal A型所占比例最高,而Triple Negative型主要以Ⅲ级为主,差异具有统计学意义（P＜0.05）。结论乳腺浸润性导管癌各分子亚型分布差异具有统计学意义,各分子亚型与其临床特征关系密切。     

Impact of pathologic complete response on disease-free survival in patients with esophagogastric adenocarcinoma receiving preoperative docetaxel-based chemotherapy

BackgroundThe aim of this study was to evaluate the impact of pathologic complete response (pCR) on outcome in patients with gastric or esophagogastric junction (EGJ) adenocarcinoma after neoadjuvant docetaxel/platin/fluoropyrimidine-based chemotherapy.Patients and methodsPatients received at least one cycle of chemotherapy for potentially operable disease. Pretreatment clinicopathologic factors and pCR were investigated. Disease-free survival (DFS), overall survival (OS) and tumor-related death were correlated with pCR.ResultsOne hundred twenty patients were included in this analysis. Eighteen patients (15%) achieved a pCR. Tumor localization in the EGJ was identified as the only significant predictor of pCR (P = 0.019). Median follow-up was 41.1 months. Median DFS and OS for all patients were 24.1 and 48.6 months, respectively. Median DFS for patients with a pCR was not reached versus 22.1 months non-pCR patients (hazard ratio, HR 0.38; 3-year DFS: 71.8% and 37.7%, respectively, P = 0.018). While OS was not significantly different, the risk for tumor-related death was significantly lower for pCR patients compared with non-pCR patients (3-year cumulative incidences of 6.4% and 45.4%, respectively, P = 0.009).ConclusionA pCR following preoperative docetaxel/platin/fluoropyrimidine indicates favorable outcome in patients with gastric or EGJ adenocarcinoma. Tumor location in the EGJ is associated with a higher pCR rate.     

Molecular Types and Neoadjuvant Chemotherapy in Patients with Breast Cancer- While Molecular Shifting is More Common in Luminal a Tumors,The Pathologic Complete Response is Most Frequently Observed in Her-2 Like Tumors

Background: Pathologic complete response (pCR) is one of the most important target end-points ofneoadjuvant chemotherapy (NACT) in patients with breast cancer (BC). In present study, we aimed to investigatethe relationship between molecular subtypes and NACT in patients with BC. Materials and Methods: Using theAkdeniz University database, 106 patients who received NACT for operable breast cancer were retrospectivelyidentified. Prognostic factors before and after NACT were assessed. According to the molecular subtypes,molecular shifting after NACT and tumoral and nodal response to NACT were analyzed. Results: The distributionof subtypes was: Luminal A, 28.3% (n=30); Luminal B, 31.1% (n=33); HER2-like, 24.5% (n=26); and basal like/triple negative (BL/TN), 16.0% (n=17). According to molecular subtypes, pCR rates in both breast and axillarywere 0%, 21.4%, 36.4% and 27.3% for luminal A, luminal B, HER2-like and BL/TN, respectively (p=0.018).Molecular subtype shifting was mostly seen in luminal A type (28.6%) after the NACT. The pCR rate in breastand axillary was significantly higher in patients with HER2-like type BC. Conclusions: In patients with HER-2like type BC, NACT may be offered in early stages. Additionally, due to molecular shifting, adjuvant treatmentschedule should be reviewed again, especially in the luminal A group.     

Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial

BackgroundPathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes.Patients and methodsPatients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses.ResultsSufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P < 0.001 in favour of pCR], DMFS (HR = 0.32, P < 0.001) and OS (HR = 0.32, P < 0.001). Chemotherapy arm was an independent predictor only for EFS (HR = 0.73, P = 0.004 in favour of T-ET). The interaction between TP53, intrinsic subtypes and survival outcomes only approached statistical significance for EFS (P = 0.1).ConclusionspCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis.ClinicalTrials.govEORTC 10994/BIG 1-00 Trial registration number NCT00017095.     

76例乳腺癌脑转移患者临床特征及预后因素分析

目的 分析乳腺癌脑转移患者临床病理特征,探讨影响乳腺癌脑转移患者的预后因素.方法 收集76例乳腺癌脑转移患者的临床病理资料,采用单因素和多因素分析影响乳腺癌脑转移患者的预后因素.结果 乳腺癌患者确诊脑转移后中位生存期为8.4个月,1年生存率为31.6%,2年生存率为7.9%,3年生存率为3.9%.多因素分析提示未放疗、PS评分≥2分、多发颅内转移灶、分子分型为Her-2型及三阴型均是乳腺癌脑转移患者的不良预后因素.Lumin-al A、Luminal B、Her-2型及三阴型乳腺癌患者中位无脑转移生存期(46.8个月、34个月、26.8个月和17.6个月,P=0.005)、确诊脑转移后生存期(16.9个月、9.5个月、7.6个月和5.5个月,P=0.001)和总生存期(64.3个月、40.9个月、31.7个月和24.1个月,P=0.001)差异均有统计学意义.结论 放疗、PS评分、脑转移灶数目及分子分型是影响乳腺癌脑转移患者的独立预后因素;与Luminal型乳腺癌相比,Her-2型及三阴型乳腺癌更易早期发生脑转移,且生存期更短.     

Association between Pathological Complete Response and Outcome Following Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients

Purpose

We aimed to determine the rate of pathological complete response (pCR), clinicopathological factors associated with pCR, and clinical outcomes following neoadjuvant chemotherapy in locally advanced breast cancer.

Methods

Medical records of patients who had undergone neoadjuvant chemotherapy for breast cancer between January 2007 and September 2011 were retrospectively reviewed, and the pCR rates were calculated according to three sets of criteria: the National Surgical Adjuvant Breast and Bowel Project (NSABP), the MD Anderson Cancer Center (MDACC), and the German Breast Group (GBG). Tumors were classified as luminal A like, luminal B like, human epidermal growth factor receptor 2 (HER2), or triple-negative. pCR and clinical outcome, including overall survival (OS) and disease-free survival (DFS) rates were analyzed at the median follow-up of 54.2 months.

Results

Of a total of 179 patients who had received neoadjuvant chemotherapy, 167 patients (93.3%) had locally advanced breast cancer and 12 patients (6.7%) had early-stage breast cancer. The majority of patients (152 patients, 89.4%) received anthracycline-based neoadjuvant chemotherapy. The objective clinical response rate was 61.5%, comprising clinical partial response in 5.5% and clinical complete response in 3.9% of patients. Twenty-one (11.7%), 20 (11.2%), and 17 patients (9.5%) achieved pCR according to NSABP, MDACC, and GBG definitions, respectively. pCR rates, as defined by NSABP, according to breast cancer subtype were 4.4%, 9.7%, 24.2%, and 19.2% in luminal A like, luminal B like, HER2, and triple-negative subtypes, respectively. Patients who achieved pCR had significantly better DFS (5-year DFS rates, 80% vs. 53%, p=0.030) and OS (5-year OS rates, 86% vs. 54%, p=0.042) than those who did not.

Conclusion

The pCR rate following neoadjuvant chemotherapy for breast cancer in Thai women attending our institution was 11.7%; pCR was more frequently observed in HER2 and triple-negative breast tumor subtypes. Patients who achieved pCR had significantly improved survival.     

Long-term outcome of the REMAGUS 02 trial,a multicenter randomised phase II trial in locally advanced breast cancer patients treated with neoadjuvant chemotherapy with or without celecoxib or trastuzumab according to HER2 status

BackgroundThe REMAGUS-02 multicenter randomised phase II trial showed that the addition to neoadjuvant chemotherapy (NAC) of trastuzumab in patients with localised HER2-positive breast cancer (BC) increased the pathological complete response (pCR) rate and that the addition of celecoxib in HER2-negative cases did not increase the pCR rate. We report here the long-term follow-up results for disease-free survival (DFS) and overall survival (OS).Patients and methodsFrom 2004 to 2007, 340 stage II–III BC patients were randomly assigned to receive neoadjuvant EC-T (four cycles of epirubicin–cyclophosphamide followed by four cycles of docetaxel) +/− celecoxib in HER2-negative cases (n = 220) and ± trastuzumab in HER2-positive cases (n = 120). From September 2005, all patients with HER2-positive BC received adjuvant T (n = 106).ResultsMedian follow-up was nearly 8 years (94.4 months, 20–127 m). In the HER2-negative subgroup, addition of celecoxib was not associated with a DFS benefit. Favourable factors were smaller tumour size, expression of progesterone receptor status (PgR) and pCR. In the HER2-positive population, neoadjuvant trastuzumab was not associated with a DFS benefit. Axillary pCR was the only prognostic factor associated with DFS in this group [HR = 0.44, 95% CI = 0.2–0.97], p = 0.035]. To note, DFS and OS were significantly higher in the HER2-positive than in HER2-negative BC patients (HR = 0.58 [0.36–0.92], p = 0.021).ConclusionCelecoxib combined with NAC provided neither pCR nor survival benefit in patients with HER2-negative BC. Absence of PgR is a major prognostic factor. Neoadjuvant trastuzumab increased pCR rates without translation into a DFS or OS benefit compared with adjuvant trastuzumab only. Axillary pCR could be a more relevant surrogate of survival than in the breast in HER2-positive population. A retrospective comparison shows that patients with HER2-positive tumours have a better outcome than HER2-negative BC patients showing the impact of trastuzumab on the natural history of BC.     

Peripheral Blood Cell Ratios as Prognostic Indicators in a Neoadjuvant Chemotherapy-Treated Breast Cancer Cohort

Breast cancer represents a heterogeneous condition in which the interaction between host immune response and primary oncogenic events can impact disease progression. Ratios of systemic blood-based immunocytes have emerged as clinically-relevant prognostic biomarkers in cancer patients. The NLR (neutrophil-to-lymphocyte ratio) has been shown to be prognostic in a variety of cancers, including breast cancer. However, evaluation of the prognostic value for overall survival (OS) and disease-free survival (DFS) of other key immunocyte ratios—neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-white cell count ratio (NWR), lymphocyte-to-white cell count ratio (LWR), monocyte-to-white cell count ratio (MWR), platelet-to-lymphocyte (PLR)—by breast cancer subtypes in a neoadjuvant chemotherapy (NAC) cohort remains to be fully explored. An NAC-treated breast cancer cohort, comprised of Luminal A, Luminal B, HER2-positive, and triple negative/basal breast cancers, treated at a tertiary referral center (minimum 3-year follow-up), was used to calculate immunocyte ratios and immunocyte cut-off values, calculated with >80% specificity (using decision tree modeling). The association with subtype-specific OS, DFS, and tumor grade was analyzed using cut offs calculated using both receiver operating characteristic curves and decision tree modelling. Decision tree calculated ratios showed that LMR (5.29) and MWR (0.06) were significantly associated with Luminal A OS (p = 0.004 and p = 0.022) and DFS (p = 0.004 and p = 0.022), and Luminal B OS (p = 0.027 and p = 0.008) and DFS (p = 0.005 and p = 0.007). NLR (1.79) and LWR (0.30) were significantly associated with HER2-positive OS (p = 0.013 and p = 0.043). NLR (1.79) and NWR (0.62) were significantly associated with DFS (p = 0.035 and p = 0.021). No significant association we observed between any immunocyte ratio in the triple negative cohort. Our results demonstrate the subtype-specific prognostic value of immunocyte ratios in NAC-treated breast cancer patients. Further validation of immunocyte ratios will provide clinicians with a new prognostic aid for disease management and monitoring.