乳腺癌新辅助化疗后临床评价与病理评价的差异分析

目的 探讨乳腺癌新辅助化疗后,临床疗效评价与病理评价之间存在差异的病理学基础.方法 收集中国医学科学院肿瘤医院2005年6月至2007年12月施行乳腺癌新辅助化疗的209例.新辅助化疗前均行核芯针穿刺活检.化疗结束后4周内实施乳腺癌根治术.新辅助化疗前后均对乳腺原发灶进行临床体检、乳腺X线检查和(或)超声检查.实施新辅助化疗后,依实体瘤的疗效评价标准(RECIST,1.1版)对乳腺癌原发灶进行临床疗效评价,依Miller和Payne(MP)分级系统进行病理评价.应用SPSS 15.0软件分析临床评价与病理评价的相关性.结果 (1)新辅助化疗后依临床体检结果进行临床评价:完全缓解33例,部分缓解124例,疾病稳定41例,疾病进展11例.(2)新辅助化疗前后均行乳腺X线检查87例,依乳腺X线检查进行临床评价:完全缓解8例,部分缓解42例,疾病稳定37例.(3)新辅助化疗后MP分级病理评价:1级14例,2级35例,3级106例,4级36例,5级18例.(4)临床体检相关的临床评价与病理评价存在统计学相关性(x2=33.668,P=0.001),乳腺X线检查相关的临床评价与病理评价存在统计学相关性(x2=22.404,P=0.004).(5)新辅助化疗病理评价与X线检查相关临床评价存在差异的病理学改变有:残存浸润癌以脉管瘤栓为主要表现形式;伴有大片黏液湖形成的黏液腺癌;导管内癌残存,伴明显沙砾样钙化及周围组织的沙砾样钙化;间质结节状纤维化等.结论 乳腺癌新辅助化疗的临床评价与病理评价存在统计学相关性.两者之间的差异有相应的病理学基础.伴有大片黏液湖形成的黏液腺癌、导管内癌的残存伴沙砾样钙化及间质结节状纤维化可能是临床评价低估治疗疗效的原因之一;而残存癌表现为脉管瘤栓可能是临床评价高估治疗疗效的原因之一.     

Ⅰb2/Ⅱa期宫颈癌56例新辅助化疗后病理观察及疗效评价

目的 研究宫颈癌新辅助化疗(NACT)后病理形态改变及对病理诊断的影响,评价宫颈癌化疗组织学疗效评判标准.方法 对56例Ⅰb2/Ⅱa期局部晚期宫颈癌患者NACT手术前后病理切片进行形态观察和组织学疗效评价,并与影像学/妇科检查对化疗疗效评价结果进行比较.结果 56例局部晚期宫颈癌患者NACT后组织学3级/重度改变11例(19.6%),2级/中度改变24例(42.9%),1级/轻度改变13例(23.2%),0级/无变化8例(14.3%).组织学评价总有效率62.5%(35/56),影像学/妇科检查评价总有效率67.9%(38/56),组织学与影像学/妇科检查有效符合30例,无效符合14例,总符合率78.6%(44/56).组织学有效、影像学/妇科检查无效4例(7.1%,4/56),组织学无效、影像学/妇科检查有效8例(14.3%,8/56).化疗有效病例癌组织呈现从密集、拥挤、生长活跃到变性、坏死、稀疏,消融、结构逐渐恢复正常的特点.结论 宫颈癌患者NACT后大部分病例有明显的病理形态改变,影响术后病理诊断,组织学疗效评价与影像学/妇科检查评价存在一定差异,推荐采用宫颈癌组织学疗效评价标准.

Abstract：

Objective To investigate the histological changes of cervical cancer after neoadjuvant chemotherapy (NACT) and to establish histological criteria for interpretation of chemotherapeutical effects.Methods Fifty-six patients with FIGO stage Ⅰb2-Ⅱa cervical cancers treated by NACT and subsequent radical surgery were retrospectively analyzed, in which the pre- and post-chemotherapeutic histopathological changes were assessed. Results The post-chemotherapeutic histopathological changes of 56 cases included grade 3 effects in 11 cases ( 19.6% ), grade 2 in 24 cases (42.9% ), grade 1 in 13 cases (23.2%) and no response in only 8 cases ( 14.3% ). The histologic response rate was 62.5% (35/56) and the overall clinical response rate was 67.9% (38/56). The overall coincidence by both criteria was 78.6% (44/56).Four cases (7.1%, 4/56) had only histological response and 8 cases ( 14.3%, 8/56) had response by imaging. In comparison with the pre-chemotherapy specimens, the chemotherapy-associated histologicalchanges included shrinkage and scattering of tumor nests, decrease of tumor cellularity, tumor cell degeneration and necrosis. Conclusions The histological changes in locally advanced cervical cancers induced by NACT are significant, which may challenge the diagnosis in the final specimens. There are some discreqancies between the histological criteria and imaging/gynecological ones for the therapeutic evaluation of cervical cancers,and it is thus recommended to use the pathological criteria for clinic practice.     

核芯针活检在乳腺癌新辅助化疗前的组织学诊断评价

目的 评价核芯针活检(CNB)作为乳腺癌新辅助化疗前组织病理学诊断依据的价值.方法 收集2005年6月至2007年1月本院人组新辅助化疗患者119例,化疗前以CNB作为组织学诊断依据;化疗后乳腺改良根治标本按Miller和Payne分级系统标准取材;每例化疗前后病理切片均由两名主检医师双盲法独立诊断,并比较其诊断的符合率.结果 CNB诊断为癌110例,其中浸润性癌105例,导管内癌5例.治疗前后浸润性癌的诊断符合率为97.2%(105108).结论 CNB在乳腺癌新辅助化疗术前对于明确病变的良恶性具有诊断优势,对鉴别肿瘤组织是否为浸润性癌具有重要参考价值.     

乳腺癌新辅助化疗前后组织病理学与分子标志物表达意义的探讨及对比分析

目的 探讨乳腺癌新辅助化疗前核芯针穿刺活检(CNB)标本和化疗后手术切除标本的病理类型、病理分级、分子标志物表达及其改变与治疗反应病理评价的关系.方法 收集209例接受新辅助化疗的乳腺癌患者CNB和手术切除标本,评价其病理类型、病理分级、治疗反应病理评价信息(MP分级系统);应用免疫组织化学方法 (MaxVision二步法)检测上述标本分子标志物雌激素受体(ER)、孕激素受体(PR)和HER2的表达信息,应用SPSS 15.0软件进行相关统计学分析.结果 (1)新辅助化疗后治疗反应病理评价分别为MP1级14例,MP2级35例,MP3级106例,MP4级36例,MP5级18例.(2)CNB标本的ER表达与治疗反应病理评价呈负相关(χ2=33.083,P=0.001);手术切除标本各类信息与治疗反应病理评价未见统计学相关性(P>0.05);(3)化疗后手术切除标本信息均可发生改变,病理类型、病理分级发生变化病例所占比例分别为6.8%(9/132)和34.9%(30/86);ER、PR、HER2表达发生改变的比例分别为42.4%(75/177)、55.4%(98/177)和26.6%(46/173),仅HER2表达改变的差异有统计学意义(P=0.049).上述信息改变与治疗反应病理评价无关(P>0.05).结论 CNB标本对预测肿瘤治疗反应的病理评价具有重要价值.化疗后肿瘤的信息均可发生改变,因此有必要在新辅助化疗后重复确认肿瘤组织的病理类型及病理分级,并应用免疫组织化学方法 重复检测化疗后手术切除标本的分子标志物表达.

Abstract：

Objective To investigate the relationship between the pathologic responses and histologic type, grade, the expression of ER, PR and HER2 and their changes in breast carcinoma before and after neoadjuvant chemotherapy (NAC). Methods Two-hundred and nine cases of breast cancer with NAC were analyzed and clinical, pathologic data were evaluated based on the Miller and Payne (MP) grading system. The expression of ER, PR and HER2 in the cancers before and after NAC were detected by immunohistochemistry (MaxVision method). SPSS 15.0 software was used to conduct statistical analysis. Results (1) Pathologic responses to the NAC were graded as MP1 (14 cases), MP2 (35 cases), MP3 (106 cases), MP4 (36 cases) and MP5 (18 cases); (2) The expression of ER in core needle biopsy had related negatively to the pathologic response (χ2=33.083, P=0.001). However, the histologic type, grade, ER and PR status, and HER2 expression in surgically-removed specimens had not related to the pathologic response (P>0.05); (3) After NAC, the pathologic type and grade changed in 6.8% (9/132) and 34.9% (30/86) of the cases, and the rates of changes in the expression of ER, PR and HER2 were 42.4% (75/177), 55.4% (98/177) and 26.6% (46/173), respectively. Only the expression of HER2 had significant difference between before and after neoadjuvant chemotherapy (P=0.049). The changes in other data had no relationship with the pathologic response (P>0.05). Conclusions Analysis of core needle biopsy can provide important information to predict the pathologic responses to the NAC. The pathologic appearance, grade, ER, PR and HER2 in breast carcinoma may change after NAC. It is necessary to examine the histologic type, grade and the expression of ER, PR and HER2 after NAC once more.     

乳腺癌新辅助化疗组织学疗效评价研究

目的 探讨乳腺癌新辅助化疗后根治标本的组织学疗效评价标准.方法 收集2005年6月至2007年6月乳腺癌新辅助化疗154例档案,其中改良根治术139例,保乳手术15例.化疗结束后4周内实施乳腺根治术.按照Miller and Payne(MP)分级系统的标准规范进行取材、制片和按该系统组织学疗效评价标准进行分级评价,同时与既往应用的肿瘤治疗反应评价系统(既往评价系统)进行比较.对所有病例进行常规随访.应用SPSS 13.0软件进行统计学处理.结果 (1)154例手术标本所获得的组织学疗效评价信息:MP分级系统1级12例(7.8%)、2级33例(21.4%)、3级64例(41.6%)、4级31例(20.1%)、5级14例(9.1%);既往评价系统分别为轻度治疗反应51例(33.1%)、中度治疗反应71例(46.1%)、重度治疗反应32例(20.8%).MP分级系统与既往评价系统各组病例比例之间存在统计学相关(X2=186.660,P<0.01).(2)154例患者中147例获得随访信息(95.5%),随访时间16～38个月;其中14例出现术后复发、远处转移或死亡.MP分级系统5个级别组与患者生存状态均相关(X2=11.612,P=0.020),既往评价系统3个级别组与患者生存状态均无关(X2=0.881,P=0.644).结论 MP分级系统可以用于肿瘤化疗后的组织学疗效评价,与预后相关.     

子宫乳头状浆液性癌临床病理分析及其辅助疗法探讨

目的 探讨子宫乳头状浆液性癌的临床病理特点及其合理疗法,以提高对该病的认识.方法 收集61例子宫乳头状浆液性癌,全面手术病理分期并随访4～9年,采用HE和免疫组织化学(EnVision法)染色,进行镜下观察,结合术后治疗方案和随访资料进行临床病理分析.结果 61例患者均为绝经后妇女,中位年龄68岁,临床表现为绝经后阴道流血和(或)腹部症状,或宫颈细胞学筛查发现异常等.肿瘤直径中位数7.5 cm(范围1.2～14.8 cm),FIGO分期:Ⅰ期17例(27.9%;Ⅰ A期8.2%,Ⅰ B期14.8%,Ⅰ C期4.9%),Ⅱ、Ⅲ和Ⅳ期分别占9.8%(6/61)、32.8%(20/61)和29.5%(18/61).活检和手术标本的组织学特点与卵巢高级别浆液性乳头状癌相似,以高级别核为特征,常出现复杂的分支状乳头状结构,沙砾体出现率24.6%(15/61),免疫组织化学染色示p53和Ki-67弥漫强阳性而雌激素受体(ER)和孕激素受体(PR)阴性(均为肿瘤细胞核着色).24.6%(15/61)未见子宫肌层浸润,但其中10/15有子宫外扩散,主要累及腹膜(6/15)和淋巴结转移(9/15).深肌层浸润、淋巴结转移和脉管受累为单个预后差的指标.56例接受术后辅助治疗,化疗者42例,放疗者24例,联合放/化疗10例.化疔组和未化疗组(用或不用放疗)的中位生存期分别为66.4和32.8个月.结论 子宫乳头状浆液性癌有独特的临床和病理特征,分期、淋巴结状况、脉管受累和肌层浸润深度为主要预后指标.晚期患者和复发患者采用含有紫衫醇(单用或联合使用顺铂)的全身化疗方案,可延长患者生存期.     

乳腺癌新辅助化疗对耐药基因MDR1和MRP表达的影响

目的:探讨乳腺癌新辅助化疗对耐药基因MDR1和MRP表达的影响。方法:采用半定量RT-PCR方法检测20例乳腺癌病人新辅助化疗前、后肿瘤组织中耐药基因MDR1和MRP的表达情况,并采用自身对照研究新辅助化疗对耐药性的影响。结果:化疗前20例乳腺癌组织中有15例(75%)MDR1表达,18例(90%)MRP表达。化疗后,经自身对照检测发现,MDR1的表达无显著差异,而MRP的表达与化疗前相比有显著差异。结论:在乳腺癌中新辅助化疗对耐药基因MDR1的表达无影响,但可增加MRP的表达.     

乳腺癌新辅助治疗病理反应的标准化

<正>新辅助治疗(neoadjuvant therapy, NAT)是主要针对局部晚期或不可切除的乳腺癌,提高保乳手术机会的治疗方法^[1]。目前,除了作为局部晚期乳腺癌的一线治疗方案,NAT还可用于监测治疗反应、高效评估药物疗效^[2]。因此,美国食品药物管理局(food and drug administration, FDA)将病理完全缓解(pathological complete response, pCR)作为评估乳腺癌新辅助试验的终点,并提供了依据^[3]。     

乳腺癌病理特征与新辅助化疗疗效分析

目的 分析乳腺癌的病理特征,并探讨新辅助化疗的临床治疗效果.方法 收集90例乳腺癌患者,术前试验组48例应用TEC化疗,对照组42例CEF化疗,21d为1个周期,连续用药3个周期,观察两组患者病理特征、治疗效果及不良反应.结果 试验组治疗总有效率89.6％,对照组81.0％,差异不具有统计学意义(P＞0.05);试验组患者白细胞减少程度较对照组重,差异具有显著性(P＜0.05).结论 新辅助化疗均可缩小肿瘤体积,控制病灶转移,增加保乳机会,对乳腺癌的治疗有积极的促进作用.     

基于人工智能辅助乳腺癌新辅助治疗后肿瘤浸润淋巴细胞评估及可重复性分析

目的 对比分析人工智能(artificial intelligence, AI)显微镜辅助和显微镜下视觉评估判读乳腺癌新辅助治疗后肿瘤浸润淋巴细胞(tumor infiltrating lymphocytes, TILs),探讨利用AI结合病理医师判读新辅助治疗后TILs的临床适用性。方法 收集行新辅助治疗乳腺癌且未获得完全缓解病例50例,由9名不同级别的病理医师通过视觉评估和AI显微镜辅助评估TILs。采用组内相关系数(intra-group correlation coefficient, ICC)和Bland-Altman散点图进行一致性分析。结果 视觉评估组9名病理医师间TILs判读结果差异有统计学意义(P<0.05,ICC=0.741,95%CI=0.656～0.821),仅高级病理医师对TILs判读结果差异较小,中级及初级病理医师的TILs判读结果差异有显著性(P<0.05)。通过AI显微镜辅助判读,不同级别病理医师对TILs判读结果差异无显著(ICC=0.955,95%CI=0.931～0.971),判读结果达到优等一致性。同时,通过对比AI辅助组与视觉评估组...     

Comparison of the prognostic significance of Chevallier and Sataloff's pathologic classifications after neoadjuvant chemotherapy of operable breast cancer

Pathologic complete response (pCR) is linked to a better outcome, but its definition varies among working groups. We performed this study to validate different expressions of pCR as well as to determine the role of in situ and isolated tumor cell residues. A pathologic review was conducted on 710 operable patients with breast cancer to assess the residual disease in breast and in nodes according to the Chevallier (Ch) and Sataloff's (Sa) classifications. The pCR rate was 14.3% according to the Chevallier and 25.8% according to the Sataloff's classification. Overall survival and disease-free survival have been compared according to the pathologic response. There were significant differences between the pCR Ch(1+2) or Sa(A) and the non-pCR group. No significant difference was found between classes Ch(1) versus Ch(2) and between class Sa(A) without isolated cells versus class Sa(A) with isolated cells. Conversely, tumors histologically modified by chemotherapy were associated with a better prognosis than unmodified tumors. Finally, evidence of pCR in nodes was associated with a better prognosis. pCR should be defined as an absence of node invasion, and in the breast, either absence of tumor or tumor residue less than 5% of the tumor.     

Prognostic value of pathologic complete response and the alteration of breast cancer immunohistochemical biomarkers after neoadjuvant chemotherapy

Neoadjuvant chemotherapy(NCT) has become the standard treatment for breast cancer. The information about the tumor’s sensitivity to chemotherapy and prognostic significance based on response to therapy can be provided after individualized neoadjuvant treatment. The biomarkers are key factors in the decision-making process regarding treatment as well as important prognostic indicators. Studies have shown that patients who achieve pathological complete response(pCR) after NCT have a better prognosis. For patients who do not achieve pCR, the pathological characteristics of the residual tumor can make an effect on the survival. Furthermore, the immunohistochemical (IHC) markers of the residual diseases after primary systemic therapy might be different from the primary tumor. Estrogen receptor (ER), progesterone receptor (PR), and Ki67 can usually change after NCT, while human epidermal growth factor receptor 2(HER2) seems to be more stable. The relationship between changes in breast cancer molecular biomarkers and the prognosis after neoadjuvant therapy is not yet clear. The article will make a review about it.     

Tumor-infiltrating lymphocytes are important pathologic predictors for neoadjuvant chemotherapy in patients with breast cancer

Neoadjuvant chemotherapy or preoperative systemic therapy is increasingly considered for patients with operable breast cancer. Patients with breast cancer were examined for pathologic factors predictive of response to neoadjuvant chemotherapy, using an anthracycline-based regimen. For clinical histomorphology and biomarkers, factors were compared among 16 pathologically complete responses and 52 nonpathologically complete responses, using univariate analysis and multivariate regression analysis of principal components, using preneoadjuvant chemotherapy needle biopsy samples as follows: degree of tumor-infiltrating lymphocytes, histologic grade, biology-based tumor type (hormone receptors and HER2 [human epidermal growth factor receptor type 2]), age, clinical TNM stage, and TNM staging. In univariate analysis, high tumor-infiltrating lymphocyte, high histologic grade, and hormone receptors(-)/HER2(+) were significantly associated with pathologically complete responses (93.7%, P < .0001; 81.3%, P = .0206; 43.7%, P = .014, respectively). In multivariate principal component regression analysis, high tumor-infiltrating lymphocytes were the best independent predictor for pathologically complete responses (odds ratio, 4.7; confidence interval, 2.2-10.06; P < .0001). Among tumor-infiltrating lymphocytes and biology-based tumor types, patients with high tumor-infiltrating lymphocytes had pathologically complete responses more than nonpathologically complete responses, especially in the hormone receptors(-)/HER2(+) group. Among high tumor-infiltrating lymphocyte cases, T lymphocytes showed more predominant tendency than B lymphocytes in the pathologically complete responses cases, compared with nonpathologically complete responses cases. These findings indicate that high tumor-infiltrating lymphocytes are important predictors of pathologically complete responses to neoadjuvant chemotherapy, especially in the hormone receptors(-)/HER2(+) group.     

Prognostic value of Ki67 expression in HR-negative breast cancer before and after neoadjuvant chemotherapy

Background: Immunohistochemical (IHC) expression of Ki67 has been identified as a prognostic and predictive marker in hormone receptor (HR)-positive breast cancer, however, there is little evidence of the association of Ki67 with prognosis in HR-negative patients. We aimed to assess the benefit of Ki67 assessment in HR-negative breast cancers after neoadjuvant chemotherapy (NAC). Methods: In the present study, a total of 183 HR-negative breast cancer patients with Stage II to III that treated with anthracycline and/or taxane-based neoadjuvant chemotherapy between 2004 and 2011 were retrospectively analyzed. Endocrine therapy and trastuzumab was not administered to any patients in this study. Clinical and pathological features of the patients with breast cancer were retrieved from the hospital records. Predictive factors for NAC response and survival were analyzed. Results: Of the 183 patients, 122 (66.6%) were HR- HER2+, and 61 (33.3%) were triple-negative. The clinical response rates were similar across breast cancer subtype. Patients whose tumors contained high Ki67 expression effectively responded to NAC. Ki67 labeling index was a predictive marker for pathologic complete response (pCR). Ki67 expression showed a positive correlation with HER2 status, tumor size, lymph node status, lymphovascular invasion and tumor grade. Furthermore, high Ki67 expression in post-treatment tumors was strongly correlated with poor disease-free survival (DFS), but no correlation of Ki-67 expression with overall survival (OS) was observed. Conclusions: Our results suggest that Ki67 expression in HR-negative breast cancer may improve the assessment of pathological response after NAC, and Ki67 score in residual tumor was an independent prognosticator for DFS in the HR-negative breast cancer patients.     

In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival

Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. However, the predictive value of tumour-infiltrating lymphocytes after neoadjuvant chemotherapy for breast cancer remains unknown. We hypothesized that the nature of the immune infiltrate following neoadjuvant chemotherapy would predict patient survival. In a series of 111 consecutive HER2- and a series of 51 non-HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy, we studied by immunohistochemistry tumour infiltration by FOXP3 and CD8 T lymphocytes before and after chemotherapy. Kaplan-Meier analysis and Cox modelling were used to assess relapse-free survival (RFS) and overall survival (OS). A predictive scoring system using American Joint Committee on Cancer (AJCC) pathological staging and immunological markers was created. Association of high CD8 and low FOXP3 cell infiltrates after chemotherapy was significantly associated with improved RFS (p = 0.02) and OS (p = 0.002), and outperformed classical predictive factors in multivariate analysis. A combined score associating CD8/FOXP3 ratio and pathological AJCC staging isolated a subgroup of patients with a long-term overall survival of 100%. Importantly, this score also identified patients with a favourable prognosis in an independent cohort of HER2-negative breast cancer patients. These results suggest that immunological CD8 and FOXP3 cell infiltrate after treatment is an independent predictive factor of survival in breast cancer patients treated with neoadjuvant chemotherapy and provides new insights into the role of the immune milieu and cancer.     

ALDH1 and tumor infiltrating lymphocytes as predictors for neoadjuvant chemotherapy response in breast cancer

Many studies have reported that Aldehyde dehydrogenase 1 (ALDH1) and tumor-infiltrating lymphocytes (TIL) are related to breast cancer prognosis. However, the clinical significance of ALDH1 and tumor-infiltrating immune cells in breast cancer has not been fully investigated in patients who received neoadjuvant chemotherapy (NAC). We studied the significance of the expression of ALDH1 and the population of TIL for predicting the prognosis and chemotherapeutic response of patients with breast cancer who had received NAC. Forty patients who underwent NAC were enrolled in this study. ALDH1 and TIL (T cells and tumor associated macrophages) were evaluated before and after NAC. The influences of ALDH1 expression status and TIL populations on both prognosis and chemotherapeutic response were evaluated. ALDH1 positivity was related to estrogen receptor (p?=?0.026) and progesterone receptor negativity (p?=?0.025). Positive change of ALDH1 after NAC tended to be associated with a poor NAC response (p?=?0.078). Patients with more CD8+ T cells before NAC and fewer CD68 (+) macrophages after NAC tended to have better OS, respectively (p?=?0.086, p?=?0.096). The chemotherapeutic response and prognosis of patients with breast cancer who received NAC are thought to be determined by the tumor microenvironment. Further research with more patients and a longer study period is needed.     

The topoisomerase II alpha gene status in primary breast cancer is a predictive marker of the response to anthracycline-based neoadjuvant chemotherapy

This study aimed at evaluating the usefulness of topoisomerase II alpha (TOP2A) for predicting the effect of anthracycline-based neoadjuvant chemotherapy in breast cancer. The TOP2A status was examined using fluorescent in situ hybridization (FISH) in 14 pre-chemotherapeutic breast cancer tissues, and was also assessed by immunohistochemistry (IHC) in 14 pairs of pre- and post-chemotherapeutic breast cancer specimens. TOP2A gene aberration by IHC tended to show a correlation with pathological responses but this was not statistically significant (p=0.060). On the other hand, the low TOP2A/CEP17 ratio correlated with good pathological responses (p=0.012). TOP2A overexpression was not significantly associated with response (p=0.580). Our results thus suggest that the TOP2A/CEP17 ratio may be a useful predictor of the effects of anthracycline-based neoadjuvant chemotherapy in breast cancer.