本文選題：化生性乳腺癌 + 三陰性乳腺癌��； 參考：《大連醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:MBC(Metaplastic breast carcinoma,化生性乳腺癌)是一種發(fā)生率低、異形性明顯并且存在不同病理亞型的乳腺惡性腫瘤。TNBC(Triple negative breast carcinoma,三陰性乳腺癌)是指在免疫組織化學(xué)上缺乏ER(estrogen receptor,雌激素受體)、PR(progesterone receptor,孕激素受體)和Her-2(human epidermal growth factor receptor-2,人類表皮生長因子受體-2)表達(dá)的一種乳腺癌亞型。本研究的目的是比較化生性乳腺癌與三陰性乳腺癌(三陰性浸潤性導(dǎo)管癌和三陰性浸潤性小葉癌)的臨床病理特征、免疫組織化學(xué)特征(即ER,PR,HER-2,CK5/6,Ki-67,P53,EGFR)、治療方法及預(yù)后,分析影響化生性乳腺癌和三陰性乳腺癌3年無病生存率和3年總生存率的相關(guān)危險因素,為化生性乳腺癌和三陰性乳腺癌的診治提供參考依據(jù)。方法:選擇2005年12月至2013年12月期間大連醫(yī)科大學(xué)附屬第二醫(yī)院收治的經(jīng)手術(shù)病理證實的化生性乳腺癌患者14例,三陰性乳腺癌患者(三陰性浸潤性導(dǎo)管癌和三陰性浸潤性小葉癌)63例。入選患者不包括臨床資料不全的患者、初次診治時即存在遠(yuǎn)處轉(zhuǎn)移的患者、雙側(cè)乳腺癌患者、存在嚴(yán)重內(nèi)科疾病、男性乳腺癌患者及身體其他部位存在腫瘤的患者。比較化生性乳腺癌和三陰性乳腺癌的臨床病理特征、免疫組織化學(xué)特征(即ER,PR,HER-2,CK5/6,Ki-67,P53,EGFR)、治療方法(手術(shù)、輔助放療、化療、內(nèi)分泌治療、靶向治療)、復(fù)發(fā)和轉(zhuǎn)移情況,3年無病生存率/期和3年總生存率/期,單因素分析影響二者3年無病生存率和3年總生存率的高危因素。兩組患者ER,PR,HER-2,CK5/6,Ki-67,P53,EGFR表達(dá)情況結(jié)果均摘自醫(yī)院病理報告。其中ER或PR受體陽性標(biāo)準(zhǔn)為腫瘤細(xì)胞核染色陽性率≥l0%;對于HER2,免疫組化法檢測3+為HER2陽性,IHC-或1+為HER2陰性,IHC 2+為HER2不確定病例,需進(jìn)一步應(yīng)用FISH的方法,當(dāng)FISH顯示HER2基因擴(kuò)增則為HER2陽性;p53與Ki-67,根據(jù)腫瘤細(xì)胞核染色陽性率所占比例計算陽性率,對于p53,無細(xì)胞核染色陽性為-,細(xì)胞核染色陽性率≤25%為1+、26%-50%為2+、50%為3+,-或1+為陰性,2+或3+為陽性;對于Ki-67,腫瘤細(xì)胞核染色陽性率≥14%為陽性,細(xì)胞核染色陽性率14%為陰性;對于EGFR,腫瘤細(xì)胞膜染色陽性率≥l0%即為陽性,細(xì)胞膜染色陽性率l0%為陰性;對于CK5/6,腫瘤細(xì)胞質(zhì)染色陽性率≥l0%即為陽性,細(xì)胞質(zhì)染色陽性率l0%為陰性。疾病分期按美國癌癥分期聯(lián)合委員會(AJCC)第6版進(jìn)行分期。本回顧性研究采用SPSS 22.0軟件進(jìn)行統(tǒng)計學(xué)分析。臨床病理特征、免疫組化、治療方法及復(fù)發(fā)情況的比較采用t檢驗和x2檢驗,3年無病生存率和3年總生存率的計算采用Kaplan-Meier法,3年無病生存率和3年總生存率的比較采用log-rank檢驗法,單因素分析采用Cox回歸分析。若結(jié)果比較具有顯著差異,且p0.05,則具有統(tǒng)計學(xué)意義。結(jié)果:1.兩組患者臨床病理特征比較14例化生性乳腺癌患者中鱗狀細(xì)胞癌最多,鱗狀細(xì)胞癌患者8例(57.1%),腺鱗癌患者2例(14.3%),梭形細(xì)胞癌患者2例(14.3%),伴軟骨化生患者2例(14.3%)。三陰性乳腺癌患者中以浸潤性導(dǎo)管癌多見,其中浸潤性導(dǎo)管癌56例(88.9%),浸潤性導(dǎo)管-小葉癌4例(6.3%),浸潤性小葉癌3例(4.8%)。14例化生性乳腺癌患者年齡范圍49至89歲之間,平均年齡63.6歲,63例三陰性乳腺癌患者年齡范圍29至77歲之間,平均年齡50.3歲,二者年齡差異有統(tǒng)計學(xué)意義(p=0.001)。腫瘤體積≥T2的患者中,化生性乳腺癌患者12例(85.7%),三陰性乳腺癌患者32例(50.8%),二者差異有統(tǒng)計學(xué)意義(p0.001)。淋巴結(jié)轉(zhuǎn)移情況,化生性乳腺癌2例(14.3%)和三陰性乳腺癌30例(47.6%)初治時出現(xiàn)淋巴結(jié)轉(zhuǎn)移,二者差異有統(tǒng)計學(xué)意義(p=0.003)。腫瘤分期≥Ⅱ期的患者中,化生性乳腺癌13例(92.9%),三陰性乳腺癌患者25例(39.7%),二者差異有統(tǒng)計學(xué)意義(p0.001)。2.兩組患者免疫組織化學(xué)特征比較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%),三聯(lián)陰性[ER(-)、PR(-)、HER-2(-)]患者11例,占78.6%。P53陽性的患者中化生性乳腺癌6例(42.9%),三陰性乳腺癌40例(63.5%),二者差異沒有統(tǒng)計學(xué)意義(p=0.277)。CK5/6陽性的患者中化生性乳腺癌8例(57.1%),三陰性乳腺癌43例(68.3%),二者差異沒有統(tǒng)計學(xué)意義(p=0.372)。Ki-67≥14%的患者中化生性乳腺癌10例(71.4%),三陰性乳腺癌17例(27.0%),二者差異有統(tǒng)計學(xué)意義(p0.001)。EGFR陽性的患者中化生性乳腺癌11例(78.6%),三陰性乳腺癌16例(25.4%),二者差異有統(tǒng)計學(xué)意義(p0.001)。3.兩組患者治療方法比較14例化生性乳腺癌患者中12例(85.7%)行改良更治術(shù),2例(14.3%)行保乳術(shù),63例三陰性乳腺癌患者中48例(76.2%)行改良更治術(shù),15例(23.8%)行保乳術(shù),二者行改良根治術(shù)的差異沒有統(tǒng)計學(xué)意義(p=0.157)。14例化生性乳腺癌患者中沒有行新輔助化療的患者,63例三陰性乳腺癌的患者中3例行新輔助化療�；匀橄侔┗颊咧�12例(85.7%)行術(shù)后輔助化療,三陰性乳腺癌患者中60例(95.2%)行術(shù)后輔助化療,二者差異沒有統(tǒng)計學(xué)意義(p=0.072)�；匀橄侔┗颊咧�3例(21.4%)行術(shù)后放射治療,三陰性乳腺癌患者中20例(31.7%)行術(shù)后放射治療,二者差異沒有統(tǒng)計學(xué)意義(p=0.083)�；匀橄侔┗颊咧�3例(21.4%)行內(nèi)分泌治療,1例患者HER2陽性,但由于經(jīng)濟(jì)原因未行赫賽汀靶向治療,三陰性乳腺癌患者沒有行內(nèi)分泌治療及赫賽汀靶向治療。4.兩組患者預(yù)后分析及比較4.1復(fù)發(fā)及轉(zhuǎn)移36個月的隨訪中,化生性乳腺癌患者出現(xiàn)局部復(fù)發(fā)4例(胸壁復(fù)發(fā)3例,腋窩復(fù)發(fā)1例),出現(xiàn)遠(yuǎn)處轉(zhuǎn)移4例(肺部轉(zhuǎn)移3例,腰椎轉(zhuǎn)移1例);三陰性乳腺癌患者出現(xiàn)局部復(fù)發(fā)3例(胸壁復(fù)發(fā)1例,腋窩復(fù)發(fā)2例),出現(xiàn)遠(yuǎn)處轉(zhuǎn)移9例(肺部轉(zhuǎn)移4例,胸椎轉(zhuǎn)移3例,腦轉(zhuǎn)移2例),化生性乳腺癌較三陰性乳腺癌更易出現(xiàn)胸壁的復(fù)發(fā)(75%versus 33.3%,p0.001),遠(yuǎn)處轉(zhuǎn)移更易出現(xiàn)肺轉(zhuǎn)移(75%versus44.4%,p=0.001)。4.2生存分析4.2.1 3年無病生存曲線36個月的隨訪中,化生性乳腺癌患者中8例出現(xiàn)局部復(fù)發(fā)或轉(zhuǎn)移,三陰性乳腺癌患者中12例出現(xiàn)局部復(fù)發(fā)或轉(zhuǎn)移,化生性乳腺癌3年無病生存率42.9%,三陰性乳腺癌3年無病生存率81.0%,二者差異有統(tǒng)計學(xué)意義(p0.001)�；匀橄侔┑�3年中位無病生存期(12月)明顯短于三陰性乳腺癌(36月)。4.2.2 3年總生存曲線36個月的隨訪中,化生性乳腺癌患者死亡的有7例,三陰性乳腺癌患者死亡的有8例,化生性乳腺癌3年總生存率50%,三陰性乳腺癌3年總生存率87.3%,二者差異有統(tǒng)計學(xué)意義(p0.001)�；匀橄侔┑�3年中位總生存期(24月)明顯短于三陰性乳腺癌(36月)。5.單因素分析兩組患者3年無病生存率和3年總生存率單因素分析顯示影響化生性乳腺癌患者3年無病生存率的主要因素有年齡50歲、腫瘤大小≥T2、分期≥Ⅱ期、Ki-67≥14%、EGFR陽性、術(shù)后輔助放療;影響化生性乳腺癌患者3年總生存率的主要因素有年齡50歲、腫瘤大小≥T2、分期≥Ⅱ期、Ki-67≥14%。影響三陰性乳腺癌患者3年無病生存率的主要因素有年齡50歲、腫瘤大小≥T2、淋巴結(jié)轉(zhuǎn)移、分期≥Ⅱ期、Ki-67≥14%、EGFR陽性、CK5/6陽性、手術(shù)方式、術(shù)后輔助化療;影響三陰性乳腺癌患者3年總生存率的主要因素有年齡50歲、腫瘤大小≥T2、淋巴結(jié)轉(zhuǎn)移、分期≥Ⅱ期、Ki-67≥14%、EGFR陽性、P53陽性、手術(shù)方式、術(shù)后輔助放療和化療。結(jié)論:1.化生性乳腺癌與三陰性乳腺癌相比,患者年齡偏高,腫瘤直徑偏大,淋巴結(jié)較少轉(zhuǎn)移,分期偏晚;Ki-67比值及EGFR陽性率較高,差異有統(tǒng)計學(xué)意義;2.化生性乳腺癌的3年無病生存率/生存期、3年總生存率/生存期明顯差于三陰性乳腺癌,差異有統(tǒng)計學(xué)意義,提示化生性乳腺癌具有更高的復(fù)發(fā)風(fēng)險及更差的預(yù)后,與其年齡較高,腫瘤直徑偏大,分期偏晚,Ki-67增殖指數(shù)及EGFR表達(dá)率高有關(guān);3.化生性乳腺癌與三陰性乳腺癌相比,更易出現(xiàn)胸壁復(fù)發(fā)及肺轉(zhuǎn)移。單因素分析提示年齡、腫瘤大小、分期、Ki-67增殖指數(shù)及EGFR陽性對這兩種乳腺癌的預(yù)測價值。化生性乳腺癌最佳的治療方法并沒明確;對于三陰性乳腺癌,徹底切除手術(shù)及術(shù)后的全身化療具有治療價值,術(shù)后輔助放療及新輔助化療的價值有待進(jìn)一步明確。
[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.

【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.9

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