分子分型对乳腺癌新辅助化疗后肿瘤退缩模式的影响

  目的  探讨乳腺癌新辅助化疗（neoadjuvant chemotherapy,NAC）后不同分子分型的乳腺原发病灶退缩模式。  方法  选取2008年7月至2017年10月山东大学附属山东省肿瘤医院收治的108例ⅡA~ⅢC期乳腺浸润性导管癌行新辅助化疗后手术患者的临床病理资料,手术标本制作次连续病理大切片,电子显微镜下勾画残余肿瘤范围,三维重建残余肿瘤,评价新辅助化疗后原发肿瘤临床病理退缩模式。  结果  108例患者新辅助化疗后向心性退缩（concentric shrinkage mode,CSM）与非向心性退缩（nonconcentric shrinkage mode,NCSM）中Luminal A型分别占47.4%（9/19）与52.6%（10/19）,Luminal B HER-2阴性型、HER-2阳性型分别占53.6%（15/28）、72.7%（16/22）与46.4%（13/28）、27.3%（6/22）,HER-2阳性型分别占84.6%（11/13）与15.4%（2/13）,三阴性乳腺癌分别占80.8%（21/26）与19.2%（5/26）。  结论  Luminal B HER-2阳性型、HER-2阳性型及三阴性乳腺癌的原发肿瘤更易出现CSM,Luminal A型、Luminal B型HER-2阴性型的原发肿瘤临床病理退缩模式无显著性差异。分子分型可用于预测乳腺癌新辅助化疗后原发肿瘤的临床病理退缩模式,有助于选择新辅助化疗后适合保乳治疗的患者、降低局部复发率。      

定量动态增强磁共振评估乳腺癌新辅助化疗疗效的应用研究

背景与目的：乳腺癌的新辅助化疗(neoadjuvant chemotherapy, NAC)已成为成熟的治疗方法,但疗效评估尚未有统一有效的方法。该研究即探讨定量动态增强磁共振在乳腺癌NAC疗效评估中的价值。方法：24例术前行NAC的乳腺癌确诊患者(24例均为浸润性导管癌),分别于NAC前、第2个疗程后、化疗结束但术前3个时间点行定量动态增强磁共振检查,分析NAC前后肿瘤最长径及动态增强磁共振定量参数：容量转移常数(Ktrans)、速率常数(Kep)、血管外细胞外间隙容积比(Ve)的变化。结果：24例患者均为单侧单发乳腺癌病灶,以RECIST标准分为有效组(17个)和无效组(7个),有效组与无效组Ktrans、Kep在NAC前与第2个疗程、化疗前与化疗结束差异均有统计学意义(P<0.05),Ve在有效组与无效组治疗前后差异均无统计学意义(P>0.05)。结论：定量动态增强磁共振可用来评估NAC疗效,并且Ktrans、Kep可做到定量,使评估结果更为客观真实,但Ve对判断治疗效果未见明显优势。     

MRI对新辅助化疗后乳腺原发肿瘤退缩模式预测的准确度

背景与目的：新辅助化疗(neoadjuvant chemotherapy,NAC)可使原发肿瘤较大的乳腺癌患者获得保乳治疗(breast-conserving therapy,BCT)机会,但NAC后原发肿瘤退缩模式影响保乳率及预后。本研究旨在观察MRI对NAC后乳腺原发肿瘤退缩模式预测的准确度。方法：61例ⅡA~ⅢC期乳腺浸润性导管癌患者, NAC后手术标本制作次连续病理大切片,显微镜下勾画残余肿瘤范围,Photoshop软件配准,3D-DOCTOR软件三维重建病理及MRI图像残余肿瘤模型,评价NAC后原发肿瘤的病理退缩模式。将其分为外科pCR(无残留灶)、孤立状、结节状、团块伴散在状和弥散状。结合病理退缩模式,将临床-病理退缩模式分为退缩明显型(distinct shrinkage mode,DSM,相比NAC前原发肿瘤最长径,NAC后残余肿瘤最长径退缩比率≥50%且≤2 cm)和非退缩明显型(non-distinct shrinkage mode,NDSM)。结果：MRI和病理的退缩模式呈外科pCR、孤立状、结节状、团块伴散在状和弥散状模式分别为23例、17例、5例、9例、7例和18例、3例、13例、20例、7例(P=0.001)。MRI预测病理退缩模式的准确度、灵敏度和特异度分别为86.2%,65.6%和91.4%。MRI和病理呈DSM比例分别为62.3%和59.0%(κ=0.863,P=0.000)。MRI预测临床-病理退缩模式的准确度、灵敏度和特异度分别为91.0%、64.0%和94.8%,其中预测DSM和NDSM差异均无统计学意义(P均>0.05)。MRI预测临床-病理退缩模式的受试者工作特征(receiver operating characteristic,ROC)曲线下面积为0.928(P=0.000)。结论：NAC后MRI三维重建图像能准确模拟并预测残余肿瘤的立体空间位置,有助于选择NAC后降期BCT患者。     

磁共振与超声评估乳腺癌患者新辅助化疗后病理完全缓解价值的比较

目的:比较磁共振增强成像（MRI）和超声检查（US）评估乳腺癌新辅助化疗后病理完全缓解(pCR)价值的研究。方法:收取2013年至2016年期间我院接受MRI和B超影像学随访、手术治疗和病理检查的75例乳腺癌患者。病理检查以及MRI和US的评估基于肿瘤的最长直径。结果:增强磁共振预测乳腺癌新辅助化疗患者pCR的敏感性为76.5%(13/17,95%CI 63%~84%),特异性和准确性为91.6%(44/48,95%CI 87%~94%)和76%(57/75,95%CI 70%~81%)。超声预测pCR的敏感性58.8%(10/17,95%CI 45%~67%),特异性和准确性为82.9%(34/41,95%CI 77%~91%)和58.6%(44/75,95%CI 42%~67%)。在影像检查和病理结果的一致性分析中,手术前MRI测量的肿瘤大小与病理学大小之间存在统计学上显著关系（P<0.005,CI:0.687）。这种相关关系在MRI测量中比在US中更强（P<0.001,CI:0.927）。结论:在接受新辅助化疗患者的术前pCR和肿瘤大小评估中,磁共振增强成像准确性优于超声,在病理反应分类的一致性明显高于超声。     

基于磁共振成像乳腺癌不同分子分型的肿瘤退缩模式初探

目的 不同分子分型的乳腺癌在新辅助化疗中具有不同的生物学特征,分子分型是否影响新辅助化疗后肿瘤退缩模式鲜见报道.本研究基于磁共振成像(magnetic resonance imaging,MRI)探讨乳腺癌新辅助化疗后分子分型和肿瘤退缩模式的相关性.方法 收集2013-04-01-2015-08-30郑州大学附属肿瘤医院乳腺科行新辅助化疗患者的化疗前88例组织标本,用免疫组化法检测激素受体(ER和PR)状态、人表皮生长因子受体2(human epidermal growth factor receptor 2,HER-2)和细胞增殖核抗原Ki-67的表达水平,将分子分型分为Luminal A型、Luminal B型、ERBB2+型及Basal-like型.于新辅助化疗前,每2个周期、术前1周内行乳腺磁共振检查,观察化疗后肿瘤退缩模式.采用Fisher's精确概率法分析不同分子分型肿瘤退缩模式的差别,采用多因素Logistic回归分析肿瘤退缩模式的预测因素.结果 88例患者中,向心性退缩39例(44.3％),巢状或树枝状退缩49例(55.7％).5例Luminal A型患者中,向心性退缩4例(4/5),巢状或树枝状退缩1例(1/5);48例Luminal B型中向心性退缩17例(35.4％％),巢状或树枝状退缩31例(64.6％);17例ERBB2+型患者中向心性退缩5例(29.4％),巢状或树枝状退缩共12例(70.6％);18例Basal-like型患者中向心性退缩13例(72.2％),巢状或树枝状退缩共5例(27.8％);差异有统计学意义,x2=12.376,P=0.004.多因素Logistic回归分析提示,分子分型是肿瘤退缩模式的独立预测因素,P=0.009.MRI诊断乳腺pCR的灵敏度为57.1％,特异度为98.5％.结论 乳腺癌分子分型与新辅助化疗后肿瘤的退缩模式相关.Luminal B型、ERBB2+型更多出现巢状或树枝状退缩,Luminal A型、Basal-like型更多出现向心性退缩.     

局部晚期乳腺癌新辅助化疗后肿瘤退缩模式的病理大切片研究

[目的]探讨局部晚期乳腺癌新辅助化疗后残留病灶的退缩模式。[方法]21例初治局部晚期乳腺癌患者,分别行2~4个周期新辅助化疗。全组病例均在新辅助化疗后行乳腺癌改良根治术或标准根治术,术后标本制作病理大切片,评价残留病灶的退缩模式。[结果]18例（85.7%）患者肿瘤的退缩模式为在原肿瘤范围内的原位消散,残留肿瘤细胞密度降低并出现不同程度的变性。3例（14.3%）呈向心性退缩且周围无癌灶残留。[结论]局部晚期乳腺癌新辅助化疗后的肿瘤退缩模式大部分为在原肿瘤范围内的原位消散,但病理范围并没有缩小。     

HER-2阳性型浸润性乳腺癌新辅助化疗后肿瘤退缩模式及影响因素

目的:了解人表皮生长因子受体2（HER-2）阳性型浸润性乳腺癌（IBC）新辅助化疗（NCT）后肿瘤退缩模式并分析影响因素。方法:回顾性分析63例NCT后未达到病理学完全缓解HER-2阳性型IBC患者临床病理学资料,以病理残存肿瘤情况判定肿瘤退缩模式将其分为向心性退缩（CSM）及非向心性退缩（NCSM）,分析肿瘤退缩模式的影响因素。结果:本研究中CSM 41例（65.08%,41/63）。单因素分析:不同NCT前T分期、HER-2表达状态及是否联合曲妥珠单抗治疗组间CSM发生率具有统计学差异（P＜0.05）,而不同年龄、体质量指数、NCT前腋窝淋巴结转移状态、HR及Ki67表达状态组间肿瘤退缩模式差异无统计学意义（P＞0.05）;多因素分析显示:NCT前T2组较T3组CSM发生率更高（OR=10.542,P=0.002）,NCT联合曲妥珠单抗组CSM发生率更高（OR=0.190,P=0.031）,不同HER-2表达状态组间肿瘤退缩模式差异无统计学意义（P＞0.05）。结论:肿瘤较大的HER-2阳性型IBC患者经NCT后拟行保乳手术者应加强术前检查评估肿瘤退缩模式,且在NCT治疗方案选择上应联合曲妥珠单抗靶向治疗,以期降低局部复发风险。     

磁共振功能成像预测乳腺癌新辅助化疗疗效的研究进展

正乳腺癌是一个在世界范围内严重危害女性健康的恶性肿瘤。近20年来,全球乳腺癌发病率以3.1%的速度递增,已跃居女性恶性肿瘤发病率的首位。国际癌症研究机构(International Agencyfor Research on Cancer,IARC)最新公布的数据表明,2008年全球约有138万乳腺癌新发病例,在西欧,其发病率高达89.7/10万。在我国,上海乳腺     

乳腺癌新辅助化疗中肿瘤标志物检测的临床意义

目的检测肿瘤标志物在新辅助化疗乳腺癌中的表达,探讨新辅助化疗患者中ER、PR、c-erbB2和Ki67的表达及临床意义.方法用免疫组织化学法检测ER、PR、c-erbB2和Ki67在89例新辅助化疗乳腺癌组织中的表达状况,分析上述指标与化疗的关系.结果新辅助化疗总有效率89.9%,其中完全缓解CR32.6%,部分缓解PR57.3%,病理完全缓解pCR17.9%,疾病稳定SD10.5%,无恶化病例.ER/PR表达与疗效有关（P〈0.05）,c-erbB2、Ki67表达与化疗疗程无关.结论激素受体阴性者对新辅助化疗的敏感性较高,新辅助化疗肿瘤标志物的检测可以为临床评价疗效判断预后提供依据.     

磁共振弥散加权成像监测乳腺癌新辅助化疗疗效的应用价值

目的 探讨磁共振弥散加权成像(DWI)监测乳腺癌新辅助化疗的早期疗效及评估化疗后残留病灶的价值.方法 前瞻性选取88例术前进行新辅助化疗的乳腺癌患者的89个病灶,用DWI直方图分析化疗过程中肿瘤多层面表观弥散系数(ADC)值的变化,随访新辅助化疗的疗效.比较按DWI图重建所测肿瘤体积与术后病理测量肿瘤体积的相关性.结果 89个乳腺癌病灶中,化疗有效68个,无效21个.化疗有效组和无效组患者在化疗前的肿瘤ADC值分别为(1.049±0.135)× 10-3 mm2/s和(1.171±0.134)×10-3mm2/s,差异有统计学意义(t=-2.731,P=0.009).全组患者化疗前的肿瘤ADC值为(1.087±0.146)×10-3 mm2/s,肿瘤退缩率为70.4%±55.1%,两者呈负相关(r=-0.430,P=0.025).有效组化疗前、化疗1个疗程后和化疗结束时的肿瘤ADC值差异均有统计学意义(均P<0.05).无效组化疗前、化疗1个疗程后和化疗结束时的肿瘤ADC值差异均无统计学意义(均P>0.05).DWI监测化疗结束后残存肿瘤体积与病理结果高度相关(r=0.749,P<0.01).结论 DWI可在乳腺癌新辅助化疗早期通过ADC值变化来监测肿瘤对治疗的反应,评估残存肿瘤大小,从而评价或预测新辅助化疗的疗效.     

乳腺癌组织中端粒酶逆转录酶的表达及新辅助化疗后的变化

背景与目的:乳腺癌组织端粒酶逆转录酶(hTERT)在乳腺癌患者新辅助化疗中的作用仍不清楚.本研究探讨新辅助化疗对hTERT表达的影响.方法:2004年2月-2007年6月对53例可手术女性乳腺癌患者采用CEF方案新辅助化疗3个周期,采用RT-PCR和免疫组化法检测化疗前、后乳腺癌组织中hTERT的mRNA和蛋白表达变化.结果:新辅助化疗前癌组织中hTERT mRNA和蛋白的阳性表达率分别为77.4%、73.6%,两者间差异无显著性(P=0.791),而采用Spearman相关检验两者呈显著正相关(r=0.289,P=0.036).新辅助化疗后hTERT mRNA和蛋白阳性表达率(28.3%,22.6%)均显著低于新辅助化疗前.hTERT mRNA及蛋白阳性表达的患者新辅助化疗有效率显著低于hTERT mRNA及蛋白阴性表达者(P值均<0.05). 结论:新辅助化疗后hTERT基因明显下调;hTERT阴性表达患者新辅助化疗疗效更明显,可作为预测新辅助化疗疗效的一个重要参考指标.     

乳腺癌患者化疗后的心理痛苦与其生活质量之间的关系分析

目的 探讨乳腺癌患者化疗后不同程度的心理痛苦与其生活质量之间的关系。方法以本院2015年3月至2016年3月62例完成6个周期标准化疗的乳腺癌术后患者为研究对象,在化疗后分别完成心理痛苦温度计（DT）及乳腺癌生活质量量表（FACT-B）的测查,根据DT是否≥4分分为高分组和低分组,比较两组间生活质量的差异,同时分析心理痛苦与生活质量的相关性。结果 62例患者中有2例未完成问卷调查剔除。60例低分组和高分组患者生活质量的评分分别为（124.3±11.2）分和（89.5±15.6）分,组间的差异有统计学意义（t=10.06,P＜0.05）。60例患者的心理痛苦评分与生活质量评分呈显著负相关（r=-0.949,P＜0.05）。结论 乳腺癌患者化疗后存在不同程度心理痛苦,且心理痛苦的评分与其生活质量密切相关。     

乳腺癌新辅助化疗后细胞增殖与凋亡的变化及临床意义

目的：观察乳腺癌患者新辅助化疗前后细胞增殖及凋亡的变化，分析与化疗疗效的关系。方法：51例乳腺癌患者术前经Mammotome穿刺活检确诊，在CEF方案新辅助化疗前及化疗2个周期后分别进行癌组织中Ki-67的免疫组织化学染色和TUNEL原位细胞凋亡检测，并评价化疗疗效。结果：新辅助化疗前Ki-67阳性表达率及凋亡指数（AI）分别为23．2％和34．1％，化疗2个周期后Ki-67阳性表达率及A1分别为7．8％和67．5%，两者差异有统计学意义，P=0．004，P=0．006；化疗疗效临床CR5例，PR40例，SD6例，无疾病进展期病例，新辅助化疗疗效与Ki-67表达下降及肿瘤细胞凋亡增加显著相关。结论：新辅助化疗可明显抑制乳腺癌细胞的增殖，诱导凋亡，与化疗疗效密切相关。     

网织红细胞在乳腺癌化疗前后的变化及临床意义

目的 了解乳腺癌患者化疗前后网织红细胞的变化及临床价值.方法 采用流式细胞术检测33例乳腺癌患者化疗前后网织红细胞的含量,采用血液分析仪检测外周血的自细胞变化.结果 化疗后第6、10天白细胞进行性明显下降(P＜0.01),第14天较第10天已逐渐回升(P＜0.05),但仍明显低于化疗前水平(P＜0.01);而网织红细胞第6、10天较化疗前明显下降(P＜0.01),但第10天较第6天无差异(P＞0.05),第14天恢复至化疗前水平(P＞0.05).结论 网织红细胞的变化可作为乳腺癌患者化疗后骨髓抑制和恢复的较敏感指标.     

Relationship between IHC4 score and response to neo-adjuvant chemotherapy in estrogen receptor-positive breast cancer

Aims

To determine whether IHC4 score assessed on pre-treatment core biopsies (i) predicts response to neo-adjuvant chemotherapy in ER-positive (ER+) breast cancer; (ii) provides more predictive information than Ki67 alone.

Methods

113 patients with ER+ primary breast cancer treated with neo-adjuvant chemotherapy at the Royal Marsden Hospital between 2002 and 2010 were included in the study. Pathologic assessment of the excision specimen was made for residual disease. IHC4 was determined on pre-treatment core biopsies, blinded to clinical outcome, by immunohistochemistry using quantitative scoring of ER (H-score), PgR (%) and Ki67 (%). Determination of HER2 status was made by immunohistochemistry and fluorescent in situ hybridization for 2+ cases. IHC4 and Ki67 scores were tested for their association with pathological complete response (pCR) rate and residual cancer burden (RCB) score.

Results

18 (16%) of the 113 patients and 8 (9%) of the 88 HER2-ve cases achieved pCR. Ki67 and IHC4 score were both positively associated with achievement of pCR (P < 10^?7 and P < 10^?9, respectively) and RCB0+1 (P < 10^?5 and P < 10^?9, respectively) following neo-adjuvant chemotherapy in all patients. Rates of pCR+RCB1 were 45 and 66% in the highest quartiles of Ki67 and IHC4 scores, respectively. In ER+HER2-ve cases, pCR+RCB1 rates were 35% and in the highest quartile of both Ki67 and IHC4. There were no pCRs in the lower half of IHC4 or Ki67 scores.

Conclusions

IHC4 was strongly predictive of pCR or near pCR in ER+ breast cancers following neo-adjuvant chemotherapy. Ki67 was an important component of this predictive ability, but was not as predictive as IHC4.

     

Correlation between magnetic resonance imaging and histopathological tumor response after neoadjuvant chemotherapy in breast cancer

AIM: To evaluate the accuracy of magnetic resonance imaging in assessing tumor response following neoadjuvant chemotherapy in patients with locally advanced breast cancer. MATERIALS AND METHODS: Twenty-six patients entered a phase II study of neoadjuvant chemotherapy, undergoing bilateral breast magnetic resonance imaging before therapy and before surgery. Tumor response was classified using RECIST criteria, using tumor size at magnetic resonance imaging. The latter was then compared to residue found at histopathological examination. RESULTS: Magnetic resonance imaging showed 6 (23%) complete responses, 17 (65%) partial responses, 3 (11.5%) disease stabilizations and no disease progressions. Twenty-three tumors (88.5%) were considered responsive and 3 (11.5%) unresponsive. Pathological tumor response was: 6 complete responses (23%), 17 partial responses (65%), 2 stable disease (8%), 1 progression (4%). When results of the preoperative magnetic resonance imaging were compared to pathological tumor response, magnetic resonance imaging overestimated tumor size in 12 cases (46%) and underestimated it in 9 (35%). However, preoperative magnetic resonance imaging failed to detect invasive tumor in 2 false-negative cases (8%), 1 of which was multifocal. Mastectomy was performed in 12 cases: 1 case of disease progression even though the neoplasm appeared smaller at magnetic resonance imaging, 3 cases with stable disease, and 4 cases with T3 or T4 disease. The 9th patient was T2N2 with initial retroareolar disease and negative magnetic resonance imaging after chemotherapy. The 10th patient, affected by lobular cancer, was in partial remission but was T3N1. The 11th patient was 57 years old but was not interested in conservative surgery. The 12th patient requested bilateral prophylactic mastectomy due to her positive family history of breast cancer. CONCLUSIONS: Magnetic resonance imaging of the breast allowed conservative surgery in 54% of the patients. This low value is primarily due to overestimation of tumor size, with a negative predictive value of 67% in our population. However, surgeons were able to choose conservative surgery with relative safety in cases of small residual disease.     

Simultaneous PET/MRI assessment of response to cytotoxic and hormone neo-adjuvant chemotherapy in breast cancer: a preliminary report

The aim of this study was to assess the response to cytotoxic and hormone neo-adjuvant chemotherapy in four patients with locally advanced breast cancer by simultaneous PET/MRI. Four patients with locally advanced breast cancer underwent simultaneous PET/MRI of the breast using a 3 T Biograph mMR before and after neo-adjuvant chemotherapy (two patients were treated with hormone-therapy and two patients were treated with cytotoxic chemotherapy). Morpho-structural tumoral features and tumor size were assessed; area value, metabolic (SUV and MTV) and functional (ADC, K _trans, V _e, k _ep and iAUC) data were obtained by positioning regions of interest. A comparison of all parameters between the pre- and post-treatment PET/MRI examinations and between the two different therapeutic schedules was assessed. In patients treated with cytotoxic chemotherapy and classified as PR, there was a significant reduction of post-treatment morphological, metabolic and functional parameters. In a patient treated with hormone therapy, classified as SD, there was an increase of all post-treatment perfusion parameters, a substantially stable ADC value and a poor reduction of lesion size and of maximum SUV (SUV_max) values; the last patient, treated with hormone therapy and classified as PR, showed a significant reduction of lesion size and SUV_max values with a reduction of perfusion parameters and substantially stable ADC values. Multiparametric evaluation with simultaneous PET/MRI could be a useful tool to assess the response to cytotoxic and hormone neo-adjuvant chemotherapy in patients with breast cancer. Future studies in a larger cohort of patients are warranted to confirm the results of this preliminary study.