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.     

乳腺X线检查在早期乳腺癌诊断中的价值

目的:探讨早期乳腺癌的X线诊断价值。方法:回顾性分析经手术病理证实的122个乳腺癌(114例)的乳腺X线表现,依据美国放射学会乳腺影像报告和数据系统(Breast imaging reporting and data system,BI-RADS)分类标准,进行乳腺X线判读。结果:122个乳腺癌中导管内原位癌23例(18.9%),浸润性导管癌77例(63.1%),小叶原位癌1例,浸润性小叶癌4例,乳头状癌12例,粘液癌5例。导管内原位癌乳腺X线影像学多不具备典型恶性征象,21例(91%)伴钙化,诊断BI-RADS-4a以上正确率为91%。浸润性导管癌1级多数不具备典型恶性征象,诊断BI-RADS-4a以上正确率为75%。浸润性导管癌2级(33例)和3级(40例)乳腺X线影像有相同的征象,二者较导管原位癌具有较明显的恶性征象,浸润性导管癌2级和3级诊断BI-RADS-4b以上正确率为77%。结论:按照BI-RADS分类标准判读乳腺X线影像在诊断早期乳腺癌中有重要临床意义。     

乳腺泥沙样钙化病灶53例病理分析

目的 探讨乳腺临床触诊阴性而钼靶X线提示泥沙样钙化病灶的病理组织学特点及临床意义.方法 对105例乳腺临床触诊阴性钼靶X线提示乳腺阳性病灶行定位切除活检,并对其中53例泥沙样钙化病灶行病理组织学分析,结合相应钼靶片结果探讨两者相关性.结果 105例中原位癌及浸润癌23例,非典型增生病变22例,良性病变60例;其中钼靶X线有泥沙样钙化53例,包括原位癌及浸润癌17例(32%)、非典型增生8例(15%)、良性病变28例(53%).泥沙样钙化病例占总病例数50.5%,其中原位癌及浸润癌占总原位癌及浸润癌73.9%.结论 泥沙样钙化在原位癌、浸润癌及良性病变中各有特点,表明钙化灶的不同特点与病变的不同性质有关.对那些钼靶--病理对照表现具原位癌、浸润癌倾向的泥沙样钙化病例应及时做定位活检.     

新辅助化疗后乳腺癌瘤床MRI表现与病理对比研究

目的探讨MRI评价乳腺癌新辅助化疗后残余肿瘤收缩模式的能力。方法收集48例Ⅱ、Ⅲ期浸润性导管癌患者的MRI检查资料并与全乳腺大切片对比。48例患者均采用TE方案进行4个周期的新辅助化疗,并在新辅助化疗前后进行MRI检查。48例乳腺癌患者在化疗结束后均进行乳腺癌改良根治术,术后乳腺标本取一半制成全乳腺大切片,显微镜观察残余肿瘤瘤床表现。结果新辅助化疗后残余肿瘤表现为向心型收缩、树枝型收缩。48例新辅助化疗后的残余肿瘤在MRI上表现为向心型收缩的有39例,占81. 25%;表现为树枝型收缩的有9例,占18. 75%。全乳腺大切片显示为向心型收缩的有40例(83. 33%),树枝型收缩的有8例(16. 67%),MRI与全乳腺大切片评价残余肿瘤收缩模式的相关系数为0. 906(P=7. 37×10-8)。结论 MRI能正确评价残余肿瘤的收缩模式,能为临床手术方式的制定提供重要的依据。     

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.     

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.     

1109例乳腺癌X线影像病理学分型研究

目的提高对乳腺癌X线征象的认识.方法分析1109例经病理证实的乳腺癌X线特征.结果1109例病例中,非浸润性癌66例(6.0%),早期浸润性癌74例(6.7%),浸润性特殊型癌96例(8.6%),浸润性非特殊型癌851例(76.7%),其他罕见癌22例(2%).结论乳腺X线检查对于乳腺癌,尤其是早期乳腺癌和隐性乳癌的诊断有重大价值.     

乳腺微小钙化灶活检在早期乳腺癌治疗中的应用

近年来,随着乳腺钼靶X线摄影在乳腺癌筛查及诊断中的广泛应用,越来越多的临床触诊阴性的乳腺微小钙化病灶被发现,我院自2000年3月至2005年8月完成141例病人共158处临床触诊阴性乳腺微小钙化灶的定位切除和病理活检,总结如下.     

Ki67免疫组化分析在乳腺癌治疗中的临床意义

通过分析Ki67在乳腺癌表达水平与临床病理特征相关性以及研究其在术后新辅助化疗前后的变化,探讨Ki67标记指数在乳腺癌治疗中的临床意义。采取免疫组化法(SP法)检测2012年后该院的246例乳腺癌患者的336例乳腺癌病理组织中Ki67的阳性表达情况,其中包括90例患者新辅助化疗前后的组织标本。Ki67阳性比例为67.5%(166/246),Ki67的表达与肿瘤大小、淋巴结转移、组织细胞学分级和人表皮生长因子受体-2成正相关(为P0.05或P0.01),与年龄、雌激素受体、孕激素受体表达成负相关(均为P0.01),与TNM分期无明显相关性;Ki67在新辅助化疗前后的表达变化值与化疗疗效明显相关(P0.01),新辅助化疗效果越好,Ki67下降越明显。Ki67阳性表达与乳腺癌的临床病理特征有密切的相关性,对乳腺癌的早期诊断、治疗与预后有指导意义,另外术后新辅助化疗影响Ki67的表达,Ki67对预测新辅助化疗的疗效有重要意义,但其是否可以作为乳腺癌诊断预后及新辅助化疗疗效的可靠指标仍需进一步研究。     

四项肿瘤标志物在乳腺癌新辅助化疗疗效评估中的作用

乳腺癌是女性最常见的恶性肿瘤之一,严重威胁着妇女的身心健康.新辅助化疗又称术前化疗、首次化疗和诱导化疗,是指在局部治疗(手术或放疗)前进行的化疗,是具有重要意义,疗效优良的乳腺癌治疗方式之一.临床上通常通过查体、B超及钼靶X线等方法来评定新辅助化疗的疗效[1],但这些方法对设备要求高,操作过程复杂,费时,费用高,因此寻找简便有效的检测手段指导临床就显得十分迫切.近年来,CA15-3、CA125、CEA、CYFRA21-1等血清肿瘤标志物检测在乳腺癌的诊断、随访中发挥了重要的作用,将其用于乳腺癌化疗后效果判断的目前也有较多报道[2-3],而用于乳腺癌新辅助化疗疗效评价方面目前研究较为有限,为此,本文通过检测乳腺癌患者新辅助化疗前后,该四项血清标志物浓度的变化,探索利用血清标志物检测对乳腺癌患者新辅助化疗疗效进行预测、评估的方法.     

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.     

Incidence of pathologic complete response in women treated with preoperative chemotherapy for locally advanced breast cancer: correlation of histology,hormone receptor status,Her2/Neu,and gross pathologic findings

Neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer and is used increasingly for large operable breast cancer. The aim of this study was to assess the rate of pathologic complete response (pCR) in our patient population with locally advanced breast cancer and identify predictive factors for pCR after neoadjuvant chemotherapy. We studied a cohort of 205 patients and compared histologic features and biomarkers in the pretreatment biopsy with the corresponding pathologic response in the subsequent resection specimen. A pCR was defined as the absence of any microscopic evidence of tumor in the mastectomy specimen and axillary lymph node dissection. The tumor size was reduced in 60% of patients; 16 patients had a pCR. Histologic grade, histologic type, and hormone status did correlate with a pathologic response. None of the 29 invasive pure micropapillary carcinomas had a pCR. Pathologic complete response among Mexican patients with locally advanced breast cancer is low (8%), and the presence of invasive pure micropapillary carcinoma could be an independent predictor for pCR.     

Extramedullary hematopoiesis in breast after neoadjuvant chemotherapy for breast carcinoma

We report incidental extramedullary hematopoiesis (EMH) in breasts of 2 patients following neoadjuvant chemotherapy for locally advanced breast cancer. Neither of the patients had a history of hematologic disorders. After chemotherapy, one of the patients had a complete pathologic response and the other had residual carcinoma. In both cases, EMH was mostly seen as myelopoiesis in a background of chemotherapy-induced changes. In the patient with residual carcinoma, EMH was observed in the contralateral prophylactic mastectomy specimen. EMH should be considered a diagnostic pitfall in the differential diagnosis of unusual cellular infiltrates in breast after neoadjuvant chemotherapy. To our knowledge, the association of EMH and neoadjuvant chemotherapy has not been previously reported.     

Primary neuroendocrine small cell carcinoma of the breast

A 60-year-old Turkish woman presented with a left breast mass, which was considered for neoadjuvant chemotherapy. By the end of the treatment cycles, the tumor had decreased in size, and the patient underwent modified radical mastectomy with axillary lymph node dissection. Pathologic examination of the tumor revealed a small cell carcinoma with neuroendocrine features confirmed by immunohistochemical stains. Multiple axillary lymph nodes were involved by metastatic small cell carcinoma carrying the same morphologic characteristics noted in the primary breast tumor. We hereby present this case as a primary neuroendocrine small cell carcinoma of the breast. This entity occurs very rarely in the breast, and fewer than a dozen cases have been reported in the literature. Extrapulmonary small cell carcinoma of the breast is reportedly a very aggressive tumor for which no consensus for treatment has yet been drawn.     

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.     

Pathologic complete response to neoadjuvant therapy in patients with pancreatic ductal adenocarcinoma is associated with a better prognosis

In patients with pancreatic ductal adenocarcinoma (PDA) who received neoadjuvant therapy and pancreatectomy, pathologic complete response (pCR) is rarely observed and the prognostic significance of pCR is not clear. In this study, we identified 11 patients with pCR (2.5%) from 442 patients with PDA who received neoadjuvant treatment and pancreatectomy from 1995 to 2010. There were 6 men and 5 women, with a median age of 61 years. Four patients had either synchronous or history of extrapancreatic cancer. Five patients received neoadjuvant chemotherapy followed by chemoradiation, and 6 received chemoradiation alone. Ten patients had pancreaticoduodenectomy, and 1 had distal pancreatectomy. Scar and chronic pancreatitis consistent with therapy effect were present in all cases (100%). Pancreatic intraepithelial neoplasia (PanIN) 3/carcinoma in situ was present in 5 cases, and PanIN1 and PanIN2 in 5 cases. However, no residual invasive carcinoma or lymph node metastasis was identified in all cases. Follow-up information was available in 10 patients. Follow-up time ranges from 6 to 194 months (median, 63 months). During the follow-up, 3 patients died of other causes, and 1 developed a second primary PDA in the tail of the pancreas at 84 months after the initial pancreaticoduodenectomy and died at 105 months after the initial diagnosis of PDA. The other 6 patients were alive with no evidence of disease. Patients with pCR had a better survival than did those who had posttherapy stage I or IIA disease (P < .001). Patients with PDA who received neoadjuvant therapy and had pCR in pancreatectomy are rare but have a better prognosis.