化生性乳腺癌与三阴性乳腺癌的回顾性分析及比较

发布时间：2018-05-04 11:02

本文选题：化生性乳腺癌 + 三阴性乳腺癌　；参考：《大连医科大学》2017年硕士论文

【摘要】：目的:MBC(Metaplastic breast carcinoma,化生性乳腺癌)是一种发生率低、异形性明显并且存在不同病理亚型的乳腺恶性肿瘤。TNBC(Triple negative breast carcinoma,三阴性乳腺癌)是指在免疫组织化学上缺乏ER(estrogen receptor,雌激素受体)、PR(progesterone receptor,孕激素受体)和Her-2(human epidermal growth factor receptor-2,人类表皮生长因子受体-2)表达的一种乳腺癌亚型。本研究的目的是比较化生性乳腺癌与三阴性乳腺癌(三阴性浸润性导管癌和三阴性浸润性小叶癌)的临床病理特征、免疫组织化学特征(即ER,PR,HER-2,CK5/6,Ki-67,P53,EGFR)、治疗方法及预后,分析影响化生性乳腺癌和三阴性乳腺癌3年无病生存率和3年总生存率的相关危险因素,为化生性乳腺癌和三阴性乳腺癌的诊治提供参考依据。方法:选择2005年12月至2013年12月期间大连医科大学附属第二医院收治的经手术病理证实的化生性乳腺癌患者14例,三阴性乳腺癌患者(三阴性浸润性导管癌和三阴性浸润性小叶癌)63例。入选患者不包括临床资料不全的患者、初次诊治时即存在远处转移的患者、双侧乳腺癌患者、存在严重内科疾病、男性乳腺癌患者及身体其他部位存在肿瘤的患者。比较化生性乳腺癌和三阴性乳腺癌的临床病理特征、免疫组织化学特征(即ER,PR,HER-2,CK5/6,Ki-67,P53,EGFR)、治疗方法(手术、辅助放疗、化疗、内分泌治疗、靶向治疗)、复发和转移情况,3年无病生存率/期和3年总生存率/期,单因素分析影响二者3年无病生存率和3年总生存率的高危因素。两组患者ER,PR,HER-2,CK5/6,Ki-67,P53,EGFR表达情况结果均摘自医院病理报告。其中ER或PR受体阳性标准为肿瘤细胞核染色阳性率≥l0%;对于HER2,免疫组化法检测3+为HER2阳性,IHC-或1+为HER2阴性,IHC 2+为HER2不确定病例,需进一步应用FISH的方法,当FISH显示HER2基因扩增则为HER2阳性;p53与Ki-67,根据肿瘤细胞核染色阳性率所占比例计算阳性率,对于p53,无细胞核染色阳性为-,细胞核染色阳性率≤25%为1+、26%-50%为2+、50%为3+,-或1+为阴性,2+或3+为阳性;对于Ki-67,肿瘤细胞核染色阳性率≥14%为阳性,细胞核染色阳性率14%为阴性;对于EGFR,肿瘤细胞膜染色阳性率≥l0%即为阳性,细胞膜染色阳性率l0%为阴性;对于CK5/6,肿瘤细胞质染色阳性率≥l0%即为阳性,细胞质染色阳性率l0%为阴性。疾病分期按美国癌症分期联合委员会(AJCC)第6版进行分期。本回顾性研究采用SPSS 22.0软件进行统计学分析。临床病理特征、免疫组化、治疗方法及复发情况的比较采用t检验和x2检验,3年无病生存率和3年总生存率的计算采用Kaplan-Meier法,3年无病生存率和3年总生存率的比较采用log-rank检验法,单因素分析采用Cox回归分析。若结果比较具有显著差异,且p0.05,则具有统计学意义。结果:1.两组患者临床病理特征比较14例化生性乳腺癌患者中鳞状细胞癌最多,鳞状细胞癌患者8例(57.1%),腺鳞癌患者2例(14.3%),梭形细胞癌患者2例(14.3%),伴软骨化生患者2例(14.3%)。三阴性乳腺癌患者中以浸润性导管癌多见,其中浸润性导管癌56例(88.9%),浸润性导管-小叶癌4例(6.3%),浸润性小叶癌3例(4.8%)。14例化生性乳腺癌患者年龄范围49至89岁之间,平均年龄63.6岁,63例三阴性乳腺癌患者年龄范围29至77岁之间,平均年龄50.3岁,二者年龄差异有统计学意义(p=0.001)。肿瘤体积≥T2的患者中,化生性乳腺癌患者12例(85.7%),三阴性乳腺癌患者32例(50.8%),二者差异有统计学意义(p0.001)。淋巴结转移情况,化生性乳腺癌2例(14.3%)和三阴性乳腺癌30例(47.6%)初治时出现淋巴结转移,二者差异有统计学意义(p=0.003)。肿瘤分期≥Ⅱ期的患者中,化生性乳腺癌13例(92.9%),三阴性乳腺癌患者25例(39.7%),二者差异有统计学意义(p0.001)。2.两组患者免疫组织化学特征比较化生性乳腺癌患者中ER(-)11例(78.6%)、PR(-)13例(92.9%)、HER-2(-)13例(92.9%),三联阴性[ER(-)、PR(-)、HER-2(-)]患者11例,占78.6%。P53阳性的患者中化生性乳腺癌6例(42.9%),三阴性乳腺癌40例(63.5%),二者差异没有统计学意义(p=0.277)。CK5/6阳性的患者中化生性乳腺癌8例(57.1%),三阴性乳腺癌43例(68.3%),二者差异没有统计学意义(p=0.372)。Ki-67≥14%的患者中化生性乳腺癌10例(71.4%),三阴性乳腺癌17例(27.0%),二者差异有统计学意义(p0.001)。EGFR阳性的患者中化生性乳腺癌11例(78.6%),三阴性乳腺癌16例(25.4%),二者差异有统计学意义(p0.001)。3.两组患者治疗方法比较14例化生性乳腺癌患者中12例(85.7%)行改良更治术,2例(14.3%)行保乳术,63例三阴性乳腺癌患者中48例(76.2%)行改良更治术,15例(23.8%)行保乳术,二者行改良根治术的差异没有统计学意义(p=0.157)。14例化生性乳腺癌患者中没有行新辅助化疗的患者,63例三阴性乳腺癌的患者中3例行新辅助化疗。化生性乳腺癌患者中12例(85.7%)行术后辅助化疗,三阴性乳腺癌患者中60例(95.2%)行术后辅助化疗,二者差异没有统计学意义(p=0.072)。化生性乳腺癌患者中3例(21.4%)行术后放射治疗,三阴性乳腺癌患者中20例(31.7%)行术后放射治疗,二者差异没有统计学意义(p=0.083)。化生性乳腺癌患者中3例(21.4%)行内分泌治疗,1例患者HER2阳性,但由于经济原因未行赫赛汀靶向治疗,三阴性乳腺癌患者没有行内分泌治疗及赫赛汀靶向治疗。4.两组患者预后分析及比较4.1复发及转移36个月的随访中,化生性乳腺癌患者出现局部复发4例(胸壁复发3例,腋窝复发1例),出现远处转移4例(肺部转移3例,腰椎转移1例);三阴性乳腺癌患者出现局部复发3例(胸壁复发1例,腋窝复发2例),出现远处转移9例(肺部转移4例,胸椎转移3例,脑转移2例),化生性乳腺癌较三阴性乳腺癌更易出现胸壁的复发(75%versus 33.3%,p0.001),远处转移更易出现肺转移(75%versus44.4%,p=0.001)。4.2生存分析4.2.1 3年无病生存曲线36个月的随访中,化生性乳腺癌患者中8例出现局部复发或转移,三阴性乳腺癌患者中12例出现局部复发或转移,化生性乳腺癌3年无病生存率42.9%,三阴性乳腺癌3年无病生存率81.0%,二者差异有统计学意义(p0.001)。化生性乳腺癌的3年中位无病生存期(12月)明显短于三阴性乳腺癌(36月)。4.2.2 3年总生存曲线36个月的随访中,化生性乳腺癌患者死亡的有7例,三阴性乳腺癌患者死亡的有8例,化生性乳腺癌3年总生存率50%,三阴性乳腺癌3年总生存率87.3%,二者差异有统计学意义(p0.001)。化生性乳腺癌的3年中位总生存期(24月)明显短于三阴性乳腺癌(36月)。5.单因素分析两组患者3年无病生存率和3年总生存率单因素分析显示影响化生性乳腺癌患者3年无病生存率的主要因素有年龄50岁、肿瘤大小≥T2、分期≥Ⅱ期、Ki-67≥14%、EGFR阳性、术后辅助放疗;影响化生性乳腺癌患者3年总生存率的主要因素有年龄50岁、肿瘤大小≥T2、分期≥Ⅱ期、Ki-67≥14%。影响三阴性乳腺癌患者3年无病生存率的主要因素有年龄50岁、肿瘤大小≥T2、淋巴结转移、分期≥Ⅱ期、Ki-67≥14%、EGFR阳性、CK5/6阳性、手术方式、术后辅助化疗;影响三阴性乳腺癌患者3年总生存率的主要因素有年龄50岁、肿瘤大小≥T2、淋巴结转移、分期≥Ⅱ期、Ki-67≥14%、EGFR阳性、P53阳性、手术方式、术后辅助放疗和化疗。结论:1.化生性乳腺癌与三阴性乳腺癌相比,患者年龄偏高,肿瘤直径偏大,淋巴结较少转移,分期偏晚;Ki-67比值及EGFR阳性率较高,差异有统计学意义;2.化生性乳腺癌的3年无病生存率/生存期、3年总生存率/生存期明显差于三阴性乳腺癌,差异有统计学意义,提示化生性乳腺癌具有更高的复发风险及更差的预后,与其年龄较高,肿瘤直径偏大,分期偏晚,Ki-67增殖指数及EGFR表达率高有关;3.化生性乳腺癌与三阴性乳腺癌相比,更易出现胸壁复发及肺转移。单因素分析提示年龄、肿瘤大小、分期、Ki-67增殖指数及EGFR阳性对这两种乳腺癌的预测价值。化生性乳腺癌最佳的治疗方法并没明确;对于三阴性乳腺癌,彻底切除手术及术后的全身化疗具有治疗价值,术后辅助放疗及新辅助化疗的价值有待进一步明确。
[Abstract]:Objective: MBC (Metaplastic breast carcinoma, metaplastic breast cancer) is a.TNBC (Triple negative breast carcinoma, three negative breast cancer) with low incidence, obvious heteromorphism and different pathological subtypes (Triple negative breast carcinoma, negative breast cancer), which refers to the lack of ER (estrogen receptor, estrogen receptor) in the immunohistochemical staining. Ptor, progesterone receptor) and Her-2 (human epidermal growth factor receptor-2, human epidermal growth factor receptor -2) expressed in a subtype of breast cancer. The purpose of this study was to compare the clinicopathological features of human breast cancer and three negative breast cancer (three negative invasive ductal carcinoma and three negative infiltrating lobular carcinoma), immunization The study features (ER, PR, HER-2, CK5/6, Ki-67, P53, EGFR), treatment and prognosis, analysis of related risk factors affecting the 3 year disease-free survival rate and the total 3 year survival rate of three negative breast cancer and three negative breast cancer, provide a reference for the diagnosis and treatment of metaplastic breast cancer and three negative breast cancer. Methods: select the period from December 2005 to December 2013 In the second hospital affiliated to the Medical University, 14 cases of metaplastic breast cancer confirmed by operation and pathology, 63 cases of three negative breast cancer (three negative invasive ductal carcinoma and three negative infiltrating lobular carcinoma) were admitted. The patients who were selected were not included in the patients with incomplete clinical data. Patients with severe internal medical diseases, male breast cancer and other parts of the body. The clinicopathological features of the comparison of sexual breast cancer and three negative breast cancer (ER, PR, HER-2, CK5/6, Ki-67, P53, EGFR), therapeutic formula (surgery, adjuvant radiotherapy, chemotherapy, endocrine therapy, targeted therapy), recurrence, and recurrence And metastasis, 3 year disease free survival rate / period and 3 year total survival rate / period. Single factor analysis affected the 3 year disease-free survival rate and high risk factors of 3 year total survival rate in two cases. The two groups of patients with ER, PR, HER-2, CK5/6, Ki-67, P53, EGFR were all extracted from the hospital pathology report. The positive rate of ER or PR receptor was the positive rate of tumor cell nuclear staining. For HER2, 3+ was positive for HER2, IHC- or 1+ was HER2 negative, IHC 2+ was HER2 uncertainty, and FISH method should be applied further. The positive rate of nuclear staining was less than 25% 1+, 26%-50% was 2+, 50% was 3+, or 1+ was negative, 2+ or 3+ was positive; for Ki-67, the positive rate of cell nuclear staining more than 14% was positive, and the positive rate of nuclear staining 14% was negative; for EGFR, the positive rate of tumor cell membrane staining > l0% was positive, and the positive rate of cell membrane staining was negative; for CK5/6, swelling was negative. The positive rate of cytoplasmic staining was more than l0%, and the positive rate of cytoplasmic staining was l0% negative. The staging of the disease was staging according to the sixth edition of the United States cancer staging Committee (AJCC). The retrospective study used the SPSS 22 software for statistical analysis. The comparison of clinicopathological features, immunohistochemistry, treatment and recurrence was compared with t test. And X2 test, the 3 year disease-free survival rate and the 3 year total survival rate were calculated by the Kaplan-Meier method, the 3 year disease free survival rate and the 3 year total survival rate were compared with the log-rank test, and the single factor analysis was analyzed by Cox regression analysis. If the results were significantly different, and P0.05, it was of the significance of the family planning. Results: the clinicopathological features of the 1. two groups were compared. Among the 14 cases of malignant breast cancer, squamous cell carcinoma was the most, 8 cases of squamous cell carcinoma (57.1%), 2 cases of adenosscale carcinoma (14.3%), 2 spindle cell carcinoma (14.3%) and 2 cases of chondrometaplasia (14.3%). Three negative breast cancer patients were infiltrative ductal carcinoma, including invasive ductal carcinoma 56 (88.9%) and infiltrative ductus lobule. 4 cases (6.3%), 3 cases of invasive lobular carcinoma (4.8%) the age range from 49 to 89 years old in.14 cases, the average age was 63.6 years old. The age range of 63 cases of three negative breast cancer was 29 to 77 years, the average age was 50.3 years old, and the age difference of two was statistically significant (p=0.001). In patients with tumor volume more than T2, the patients with metaplastic breast cancer 12 cases (85.7%), three negative breast cancer patients (50.8%), the two differences were statistically significant (p0.001). Lymph node metastasis, 2 cases of malignant breast cancer (14.3%) and 30 cases (47.6%) of negative breast cancer (47.6%) had lymph node metastasis during the first treatment (47.6%). The difference of two was statistically significant (p=0.003). Cases (92.9%), three negative breast cancer patients (39.7%), two differences were statistically significant (p0.001).2. two, the immuno histochemical characteristics of patients with ER (-) 11 (-) 11 cases (78.6%), PR (-) 13 (92.9%), HER-2 (-) 13 (92.9%), triple negative [ER (-), PR (-), HER-2 (-)) patients accounted for 11 cases, which accounted for the patients with 78.6%.P53 positive. 6 cases of sexual breast cancer (42.9%), 40 cases with three negative breast cancer (63.5%), there were no statistically significant differences between the two (p=0.277).CK5/6 positive patients, 8 cases of metaplastic breast cancer (57.1%), three negative breast cancer 43 cases (68.3%), there was no statistically significant difference between two and three patients (p=0.372).Ki-67 > 14% patients with metaplastic breast cancer. Cases (27%), there were statistically significant differences between the two (p0.001).EGFR positive patients 11 cases of metaplastic breast cancer (78.6%), three negative breast cancer (25.4%), two of the difference was statistically significant (p0.001).3. two patients treatment methods compared with 14 cases of biological breast cancer patients, 12 cases (85.7%) underwent improved treatment, 2 cases (14.3%) breast conserving surgery, cases Three of the three negative breast cancer patients (76.2%) were treated with improved treatment, 15 (23.8%) breast conserving surgery, and the two had no significant difference in radical mastectomy (p=0.157) there was no new adjuvant chemotherapy in.14 patients with breast cancer, 63 patients with three negative breast cancer were treated with neoadjuvant chemotherapy. 1 of the patients with metaplastic breast cancer were treated. 2 cases (85.7%) underwent postoperative adjuvant chemotherapy, 60 of three negative breast cancer patients (95.2%) underwent postoperative adjuvant chemotherapy, the two difference was not statistically significant (p=0.072). 3 of the patients with metaplastic breast cancer (21.4%) underwent postoperative radiotherapy, 20 cases (31.7%) in three negative breast cancer patients (31.7%) had no statistical significance (p=0.083 3 cases (21.4%) of the patients with metaplasia of breast cancer were treated with endocrine therapy and 1 patients were HER2 positive. However, there was no Herceptin targeted therapy for economic reasons. Three negative breast cancer patients were not treated with endocrine therapy and the prognosis of Herceptin targeted treatment of.4. two patients and the comparison of 4.1 relapse and metastasis for 36 months were compared. There were 4 cases of local recurrence (3 cases of chest wall recurrence, 1 cases of axillary recurrence), 4 cases of distant metastasis (3 cases of pulmonary metastasis, 1 cases of lumbar metastasis), 3 cases of local recurrence in three negative breast cancer patients (1 cases of chest wall recrudesce, 2 cases of axillary recurrence), 9 cases of distant metastasis (4 cases of pulmonary metastasis, 3 cases of thoracic vertebra metastasis, and cerebral metastases in 2 cases). Negative breast cancer is more likely to have a recurrence of the chest wall (75%versus 33.3%, p0.001), distant metastasis is more prone to pulmonary metastasis (75%versus44.4%, p=0.001).4.2 survival analysis, 4.2.1 3 year disease free survival curve for 36 months of follow-up, 8 cases of metaplastic breast cancer have local recurrence or metastasis, and 12 cases of three negative breast cancer have local recurrence. The 3 year disease-free survival rate of metaplastic breast cancer was 42.9%, the 3 year disease-free survival rate of three negative breast cancer was 81%, the two difference was statistically significant (p0.001). The 3 year disease-free survival (December) of the metaplastic breast cancer (December) was significantly shorter than that of the three negative breast cancer (36 month) 3 years.4.2.2 3 years total survival curve, and the death of the patients with metaplastic breast cancer was dead. There were 7 cases of death and 8 cases of three negative breast cancer patients. The 3 year total survival rate was 50%, the 3 year total survival rate of three negative breast cancer was 87.3%. The difference was statistically significant (p0.001). The median survival period of 3 years (24 months) of the malignant breast cancer was significantly shorter than that of three negative breast cancer (36 month).5. single factor analysis. The single factor analysis of survival rate and 3 year total survival rate showed that the main factors affecting the 3 year disease-free survival rate of the patients with metaplastic breast cancer were 50 years old, tumor size more than T2, stage more than II stage, Ki-67 more than 14%, EGFR positive, and postoperative adjuvant radiotherapy. The main factors affecting the 3 year total survival rate of the patients with metaplastic breast cancer were 50 years old and the tumor size was more than T2, The main factors affecting the 3 year disease-free survival rate of three negative breast cancer patients were age 50 years old, tumor size of 50 years old, tumor size > T2, lymph node metastasis, stage more than II stage, Ki-67 more than 14%, EGFR positive, CK5/6 positive, operation mode and postoperative adjuvant chemotherapy, and the main factors affecting the 3 year total survival rate of three negative breast cancer patients were 50 years old. The size of tumor was more than T2, lymph node metastasis, stage more than II stage, Ki-67 more than 14%, EGFR positive, P53 positive, operation mode, adjuvant radiotherapy and chemotherapy after operation. Conclusion: compared with three negative breast cancer, the age of 1. sexual breast cancer is higher, the diameter of the tumor is larger, the lymph node is less metastasis, the stage is late, the Ki-67 ratio and the positive rate of EGFR are higher, the difference has unification The 3 year disease-free survival rate / survival period and 3 year total survival rate / survival time of the 2. adult breast cancer were significantly worse than three negative breast cancer. The difference was statistically significant. It suggested that the malignant breast cancer had higher recurrence risk and worse prognosis, the higher the age, the larger tumor diameter, the late stage, the Ki-67 proliferation index and the EGFR expression. High rate is associated with high rate; 3. breast cancer is more likely to have chest wall recurrence and lung metastases than three negative breast cancers. Single factor analysis suggests age, tumor size, staging, Ki-67 proliferation index and EGFR positive predictive value for these two kinds of breast cancer. The best treatment method for metaplastic breast cancer is not clear; for three negative breast cancer, thoroughly cut Besides surgery and postoperative systemic chemotherapy, the value of postoperative adjuvant radiotherapy and neoadjuvant chemotherapy needs to be further clarified.

【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9

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