预测乳腺癌新辅助化疗反应的临床病理和分子指标研究进展

新辅助化疗(NAC)增加了局部晚期乳腺癌患者的手术机会,改善了预后.但是,仍有一部分患者不能从目前使用的不同化疗方案中获益,导致疾病进展,从而失去永久治愈肿瘤的机会.识别与NAC反应有关的预测指标有助于区分对治疗反应不同的患者,以便实施个体化治疗.到目前为止,已证实多个因素可作为NAC反应的预测因子,包括肿瘤大小、组织...     

新辅助化疗后的病理完全缓解及其对不同分子亚型乳腺癌的预后价值

新辅助化疗已经成为乳腺癌一项重要的治疗策略,它可以为部分患者带来显著的临床获益。病理完全缓解可以检验新辅助化疗疗效,它曾被看作是乳腺癌患者新辅助治疗后临床结局的替代指标,但这方面争议颇多。为此,本文将着重从病理完全缓解的定义,不同分子亚型乳腺癌的病理完全缓解率以及预测价值进行详细综述,为临床工作提供依据。     

影响乳腺癌新辅助化疗后病理完全缓解的临床因素分析

目的:探讨影响乳腺癌新辅助化疗后病理完全缓解（pathological complete response,pCR）的临床因素。方法:回顾分析新辅助化疗并行根治性手术的120例女性乳腺癌患者的临床资料;所有患者均接受6~8周期EC-T方案化疗,化疗结束后2~4周行根治性手术。采用χ2检验及 Logistic 回归分析影响pCR和非pCR的临床因素。结果:疗效结果单因素分析显示:T分期、N分期、乳腺癌分子分型、治疗前Ki-67表达水平、治疗前血小板水平与乳腺癌新辅助化疗后肿瘤pCR率显著相关。Logistic二元回归分析发现乳腺癌非Luminal分子亚型和新辅助化疗前高血小板水平是影响乳腺癌新辅助化疗后pCR的独立预测因素。结论:乳腺癌非Luminal分子亚型和新辅助化疗前高血小板水平是影响乳腺癌新辅助化疗后pCR的决定性因素。     

乳腺癌新辅助化疗后病理完全缓解的因素分析

目的:研究代谢综合征（metabolic syndrome,MS）与乳腺癌新辅助化疗（neoadjuvant chemotherapy,NAC）病理完全缓解（pathological complete response,pCR）的关系。方法:收集2014年01月至2020年06月在哈尔滨医科大学附属肿瘤医院接受NAC后进行手术的女性乳腺癌患者526例,并收集患者的临床病理资料,根据MS诊断标准分为MS组99例与非MS组427例。采用Logistic回归模型进行单因素和多因素分析MS与pCR的关系。结果:105例患者NAC后获得pCR,其中MS组10例,非MS组95例。单因素分析显示:非MS组较MS组更易获得pCR（P=0.008）,激素受体（hormone receptor,HR）阴性、人类表皮生长因子受体2（human epidermal growth factor receptor-2,HER-2）阳性、Ki-67＞14%者更易获得pCR（P＜0.001、P＜0.001、P=0.002）。多因素分析显示:与HR阴性者相比,HR阳性者较难获得pCR（P＜0.001）;与HER-2阴性者相比,HER-2阳性者pCR率更高（P=0.033）;与非MS患者相比,合并MS患者更难获得pCR（P=0.041）。亚组分析显示:非MS组中HR阴性患者更易获得pCR（P＜0.001）。结论:HR状态、HER-2状态及MS是乳腺癌NAC后pCR的独立预测因素,合并代谢综合征的乳腺癌患者接受新辅助化疗后更难获得病理完全缓解,与长期预后相关性有待进一步研究。     

乳腺癌分子分型在新辅助化疗疗效和预后中的预测作用

[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]对接受新辅助化疗方案治疗的157例乳腺癌患者进行回顾性分析.依据免疫组化雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(Her2)表达水平将乳腺癌分为Luminal A、Luminal B、Her2阳性和三阴性4个分子分型,分析4个分子分型与临床病理因素、新辅助化疗疗效及3年生存率的相关性.[结果] 157例患者中,分子分型与肿瘤大小、淋巴结转移相关,T3～4期的三阴性型的比例高于T1～2期(P=0.003);N0、N1、N2、N3期的三阴性型的比例分别为44.4％、23.8％、25.6％和22.2％ (P=0.014).不同分子分型间新辅助化疗有效率无明显差异(P=0.632),而T分期(P=0.014)、N分期(P=0.031)与有效率明显相关.不同分子分型间新辅助化疗3年生存率有明显差异,Luminal A型最高,三阴性型最低(P=0.049).乳腺癌预后影响因素Cox回归模型分析提示分子分型(P=0.003)、年龄(P=0.007)、T分期(P=0.013)、N分期(P=0.000)是乳腺癌患者的独立预后因素.[结论]乳腺癌分子分型与肿瘤大小、淋巴结转移状态相关,能作为新辅助化疗远期疗效的独立预测因子.     

分子分型与乳腺癌新辅助化疗疗效的相关性

目的:探讨乳腺癌分子分型与新辅助化疗疗效的相关性.方法:回顾性分析81例原发乳腺癌患者,分子分型分为HER-2阳性型和三阴型、Luminal A型、Luminal B1型、 Luminal B2型,并评估其与乳腺癌新辅助化疗疗效的关系.结果:新辅助化疗疗效与各分子分型之间的相关性无统计学意义,但新辅助化疗有效率达到pCR+tpCR(%)以三阴型最高(25%),其次是HER-2阳性型(23.1%),而达到CR+PR(%)为HER-2阳性型最高(84.6%).结论:乳腺癌新辅助化疗可有效控制肿瘤,分子分型能作为乳腺癌新辅助化疗疗效的缓解独立预测因子.     

乳腺癌新辅助化疗病理完全缓解率及影响因素分析

目的:分析影响患者新辅助化疗(neoadjuvant chemotherapy, NAC)后病理完全缓解(pathologic complete remission, pCR)的相关因素,为乳腺癌(breast cancer, BC)患者应用NAC联合保乳手术治疗方案提供参考和依据。方法:研究对象来源于2013年01月至2021年12月在山西白求恩医院乳腺外科治疗的Ⅱ-Ⅲ期女性BC患者。采集患者的人口学特征、临床病理资料以及化疗相关信息,观察肿瘤原发灶的变化评价NAC的短期疗效。结果:研究共260例研究对象,保乳手术(breast-conserving surgery, BCS)率为21.9%,pCR率为18.1%。肿瘤pCR的单因素分析中,是否哺乳(P<0.05)、ER、PR、HER-2、Ki-67表达、分子分型、靶向治疗及治疗方案均与乳腺pCR相关(P≤0.01)。多因素分析中,肿瘤分子分型与肿瘤pCR显著相关(OR=0.077,95%CI:0.022～0.262)。结论:NAC可以减小肿瘤,提高保乳率及pCR率。不同分子分型的肿瘤pCR率有显著差异,尤其是在三阴性乳腺癌患者...     

影响青年乳腺癌患者新辅助化疗后病理完全缓解和预后的病理因素分析

目的:探讨影响青年乳腺癌患者新辅助化疗（neoadjuvant chemotherapy,NAC）后病理完全缓解（pathological complete response,pCR）和预后的临床病理因素。方法:回顾性分析2010年01月至2018年12月我院甲乳外科收治年龄≤35岁行NAC的女性乳腺癌患者的临床病理资料。NAC后依据Miller-Payne评分系统,将患者分为pCR组和非pCR组。探讨临床病理因素对青年乳腺癌患者pCR、复发转移和死亡的影响,同时分析pCR与无病生存期（disease free survival,DFS）与总生存期（overall survival,OS）之间的相关性。结果:168例患者中pCR 37例,pCR率为22.0%。体质量指数(body mass index,BMI)、术前淋巴结状态、雌激素受体（estrogen receptor,ER）、孕激素受体（progesterone receptor,PR）、人类表皮生长因子受体2（human epidermal growth factor receptor-2,HER-2）、Ki-67、p53及分子分型与青年乳腺癌患者NAC后的pCR率关系密切（P＜0.05）。肿瘤大小、术前淋巴结状态、ER、PR、HER-2、p53及分子分型影响患者的复发转移和死亡（P＜0.05）,同时肿瘤大小、术前淋巴结状态、组织学分级、ER、PR、HER-2、Ki-67及分子分型均是DFS和OS的独立影响因素（P＜0.05）。66例复发转移患者中pCR患者7例,占pCR患者的18.9%（7/37）,pCR组和非pCR组DFS比较差异具有统计学意义（P＜0.05）。38例死亡患者中pCR患者3例,占pCR患者的8.1%（3/37）,pCR组和非pCR组OS比较差异具有统计学意义（P＜0.05）。结论:影响青年乳腺癌患者pCR和预后的临床病理因素较多,获得pCR的患者具有更好的远期预后。     

Discrepancies Between Pathological Tumor Responses and Estimations of Complete Response by Magnetic Resonance Imaging After Neoadjuvant Chemotherapy Differ by Breast Cancer Subtype

Introduction

The influence of breast cancer (BC) subtype in discrepancies between pathologic complete response (pCR) and complete response by magnetic resonance imaging (MRI-CR) after neoadjuvant chemotherapy (NAC) have not been discussed well. We evaluated the association between BC subtype and pCR or only residual in situ lesion without invasive cancer (pCR/in situ⁺) in patients with MRI-CR (positive predictive value [PPV]).

Predictors of Pathological Complete Response to Neoadjuvant Chemotherapy in Iranian Breast Cancer Patients

Background: Achievement of pathologic complete response (pCR) in breast cancer patients receiving neoadjuvant chemotherapy (NAC) is associated with both overall survival and disease-free survival. The aim of present study was to identify clinical and pathological factors associated with achieving pCR in Iranian breast cancer patients receiving NAC. Methods: A retrospective review of all breast cancer patients treated with neoadjuvant chemotherapy between April 2012 and September 2016 at our institution was performed; 207 cases were evaluable for analysis. pCR was defined as having no residual invasive tumor in the breast surgical specimen removed following neoadjuvant therapy. Results: In univariate analysis, factors associated with pCR were age less than 35 years (p = 0.03), absence of Lymphovascular invasion (LVI) (p = 0.002) and negative hormone receptor status (p = 0.003). Hormone receptor status (P = 0.01; OR, 2.45; CI, 1.20 - 4.99) and LVI (P = 0.001; OR, 0.22; CI, 0.10 - 0.46) remained predictive variables in multivariate analysis after correction for the other variables. Conclusions: In conclusion, the results of this study suggests that presence of Lymphovascular invasion and positive hormone receptor status are associated with poorer response to neoadjuvant chemotherapy in breast cancer patients.     

系统免疫炎性反应指数对乳腺癌新辅助化疗病理完全缓解的预测作用及其与p53的关系

目的探讨系统免疫炎性反应指数(SII)对乳腺癌新辅助化疗(NAC)病理完全缓解(pCR)的预测作用及其与p53的关系。方法回顾性分析387例接受新辅助化疗及手术的女性乳腺癌患者临床病理资料。Logistic回归模型进行单因素和多因素分析。结果 72例(18.6%)患者接受新辅助化疗后获得了pCR,其中低SII组48例,高SII组24例;p53阴性组39例,阳性组33例。单因素分析显示:pCR与临床T分期、激素受体(HR)状态、人表皮生长因子受体2(HER2)、Ki67值、分子分型、p53及SII相关(均P<0.05);多因素分析显示:临床T分期、Ki67值、分子分型、p53及SII是影响乳腺癌患者pCR的独立预测因素。p53阴性的低SII组患者pCR率高于其他组。结论 SII是乳腺癌新辅助化疗病理完全缓解的独立预测因素,具有简单方便及重复性高等特点,p53阴性的低SII组患者pCR率高。     

High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer

Background.

In the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial.

Patients and Methods.

We analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinical trials of neoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2).

Results.

A basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 >50% achieved a pCR rate of 40% (36 of 91) versus a pCR rate of 19% in patients with Ki67 ≤50% (33 of 171) (p = .0004). Ki67 predictive value was especially relevant in ER-HER2− and ER-HER2+ patients (pCR rates of 42% and 64%, respectively, in patients with Ki67 >50% versus 15% and 45%, respectively, in patients with Ki67 ≤50%; p = .0337 and .3238, respectively). Both multivariate analyses confirmed the independent predictive value of the Ki67 cutpoint of 50%.

Conclusion.

Basal Ki67 proliferation index >50% should be considered an independent predictive factor for pCR reached after neoadjuvant chemotherapy, suggesting that cell proliferation is a phenomenon closely related to chemosensitivity. These findings could help to identify a group of patients with a potentially favorable long-term prognosis.

Implications for Practice:

The use of basal Ki67 status as a predictive factor of chemotherapy benefit could facilitate the identification of a patient subpopulation with high probability of achieving pathological complete response when treated with primary chemotherapy, and thus with a potentially favorable long-term prognosis.     

A Panel of Tumor Biomarkers to Predict Complete Pathological Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer

Pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients is related to a favorable prognosis. The identification of early biomarkers predictive of pathological complete response would help optimize the multimodality management of the patients. A panel of 11 tumor-related proteins was investigated by immunohistochemistry in the pretreatment biopsy of a group of locally advanced rectal cancer patients to identify early biomarkers of pathological complete response to neoadjuvant chemoradiotherapy. A mono-institutional retrospective cohort of 95 stage II/III locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy and surgery was selected based on clinical–pathological characteristics and the availability of a pretreatment tumor biopsy. Eleven selected protein marker expression (MLH1, GLUT1, Ki67, CA-IX, CXCR4, COX2, CXCL12, HIF1a, VEGF, CD44, and RAD51) was investigated. The optimal cutoff values were calculated by receiver operating characteristic curve analysis. Classification and regression tree analysis was performed to investigate the biomarker interaction. Patients presenting either Ki-67 or HIF1a or RAD51 below the cutoff value, or CXCR4 or COX2 above the cutoff value, were more likely to get a pathological complete response. Classification and regression tree analysis identified three groups of patients resulting from the combination of Ki-67 and CXCR4 expression. Patients with high expression of Ki-67 had the lowest chance to get a pathological complete response (18%), as compared to patients with low expression of both Ki-67 and CXCR4 (29%), and patients with low Ki-67 and high CXCR4 expression (70%). Pretreatment Ki-67, CXCR4, COX2, HIF1a, and RAD51 in tumor biopsies are associated with pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer. A combined evaluation of Ki-67 and CXCR4 would increase their predictive potential. If validated, their optimal cutoff could be used to select patients for a tailored multimodality treatment.     

乳腺癌新辅助化疗后同侧内乳区淋巴结病理完全缓解的预测因素及预后价值

目的 探讨乳腺癌新辅助化疗后内乳区淋巴结病理完全缓解（ipCR）的预测因素及其对预后的影响。方法 对70例伴内乳区淋巴结转移的原发乳腺癌并接受新辅助化疗患者病例资料进行回顾性分析,根据术后病理分为ipCR组和non-ipCR组。对乳腺癌新辅助化疗后同侧ipCR的预测因素,χ 2检验、Fisher及Logistic回归分别进行单因素和多因素分析,Kaplan-Meier曲线和Cox回归进行预后分析。结果 70例患者中31例获得ipCR（44.3%）。单因素分析显示,腋窝pCR、激素受体表达水平、HER2状态与ipCR有关（P<0.05）。多因素分析显示,年龄、腋窝pCR、HER2状态是ipCR的独立预测因子。ipCR组平均DFS达96.0个月（95%CI: 49.5~84.7）,明显优于non-ipCR组为67.1个月（95%CI: 81.7~110.3, P<0.05）。ipCR组复发转移风险较non-ipCR组降低87%（HR=0.13, 95%CI: 0.04~0.44, P<0.01）。ipCR、Ki67表达水平、乳房pCR是影响患者预后的独立因素。结论 新辅助化疗后是否获得ipCR与临床病理因素存在相关性。ipCR可用于预测内乳区淋巴结转移患者的预后。     

新辅助化疗与乳腺癌病理组织形态学及分子水平相关基因的表达

新辅助化疗是指在实施手术或放疗之前应用的全身性化疗,对乳腺癌有良好的近期疗效,同时为化疗药体内药敏试验提供了可靠的依据.以往对新辅助化疗疗效的评定仅限于常规镜下观察化疗后病理形态学改变的组织学评定,结合肿瘤特异性标志物的检测是一种新尝试,从不同层面对新辅助化疗后乳腺癌组织的变化进行观察,客观评价新辅助化疗对指导临床个体化化疗的作用.     

Ⅲ期可手术乳腺癌新辅助化疗的近期和远期效果

目的　探讨Ⅲ期可手术乳腺癌新辅助化疗 (NACT )的效果。方法　将 74例Ⅲ期可手术乳腺癌随机分为A组(NACT组 ,3 6例 )和B组 (对照组 ,3 8例 )。A组采用CAF(CTX/ADM /5 Fu)方案做短期NACT 2个周期 ,随后手术 ,术后辅助放疗、化疗。B组除不行NACT外 ,手术和术后其它治疗与A组相同。结果　A组 (NACT组 )客观有效率为 75 .0 % ,而且A组病理组织学改变较B组明显。 2组 5年生存率和无病生存率 (DFS)分别为 66.7%、3 6.8%和 5 5 .6%、2 6.3 %。A组均高于B组 (P <0 .0 5 )。结论　NACT能提高Ⅲ期可手术乳腺癌的疗效     

Predictive Value of IHC4 Score for Pathological Response to Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer

Purpose: This study aimed to explore the value of IHC4 in predicting pathological response after neoadjuvant chemotherapy in patients with hormonal receptor (HR)-positive breast cancer (BC). Materials and Methods: In this retrospective exploratory study, data for 68 HR-positive BC patients who received neoadjuvant chemotherapy were recorded. IHC4 scores were calculated based on estrogen receptors/progesterone receptors, Ki-67 and HER2 status. Logistic and ordinal regression analyses in addition to likelihood ratio test were used to explore associations of IHC4 scores and other clinico-pathological parameters with pathological complete response (pCR) and pathological stage. Results: Taking the 25th percentile as the cut-off, a lower IHC4 score was associated with an increased probability of pCR (low; 52.9% vs. High; 21.6%, OR=4.1, 95% CI= 1.28-13.16, p=0.018) and a lower pathological stage (OR =3.9, 95% CI=1.34-11.33, p=0.012). When the IHC4 score was treated as a continuous variable, a lower score was again associated with an increased probability of pCR (OR=1.010, 95% CI=1.001-1.018, p=0.025) and lower pathological stage (OR=1.009, 95% CI= 1.002-1.017, P=0.008). Lower clinical stage was associated with a better pCR rate that was of borderline significance (P=0.056). When clinical stage and IHC4 score were incorporated together in a logistic model, the likelihood ratio test gave a P-value of 0.004 after removal of the IHC4 score and 0.011 after removal of the stage, indicating a more significant predictive value of the IHC4 score for pCR. Conclusions: This study suggests that the IHC4 score can predict pathological response to neoadjuvant chemotherapy in HR-positive BC patients. This finding now needs to be validated in a larger cohort of patients.