Aboutthree-negativebreastcancer-毕业论文翻译

1、About three-n egative breast cancerBreast can cer is the most com mon malig nancyofwome n,its incideneehas in creasedyear by yearanddropp ing,accord ingto World HealthOrga ni zati on,theIntern ati onal Can cer Research Cen ter The latest statisticsshow that worldwide there are about 1.2 million brea

2、st can cer patie nts each year, of which 540,000 of new cases,about 50 million people each year die of the disease.Cancer Research Office of China s research data shows that in 2005 wome n with breast can cer in cide nee rate of 24.5/10 our milli on, ranking first in various types of can cer, 2000-2

3、005, the in cide nee of breast can cer in creased by 38.5%. Experts predict that 20 years after breast can cer will be the highest in cide nee of malig nant tumors in Chi na1.Breast can cer is a highly heteroge neous tumor characteristics in terms of molecular biology, morphology, immun ophe no type

4、 or resp onse to treatme nt, both the existenee of significant differences, to understand these differe nces can be more in dividualized and effective itreatme nt 2. At prese nt the comb in ati on of immune andgene expression of differentproducts,divided into fivesubtypes of breast cancer, hormonere

5、ceptor-positiveclasses, respectivelyluminalA type and luminalB type oftumor cell gene expressi on and fromthe inner tubelumi nal epithelial cells similar; HER2 over-express ing no rmal mammary gla nd geneexpressi ontype(normal-like,with high expression of basal epithelial cellgene expressionof lumin

6、al epithelial cells, while genescharacteristicof basal cell-like type, and normal breastepithelial cells express similar basal 3.Triple-negative breast cancer (TNBC was only raised in recent years, and is the estrogen receptor (ER, progestero ne receptor (PR and huma n epidermal growth factor recept

7、or 2 subtype(HER2-negativebreast cancerare, Breast can cer acco unts for about 12% -40% occur in wome n 40 years of age, a higher prevale nee in Africa n America ns, has a special biologicalbehavior and cli ni calpathological features, cli nicalmani festati onsof anaggressive course of disease , hig

8、h incideneeof localrecurre neeand dista nt metastasis, poor prog no sistha nother types of breast cancer, endocrinetherapy andan ti-HER2targeted therapy 4. TNBC and basal-likebreast can cer (BLBC in morphology,immun ophe no type,and so there a lot of similarities.BLBC mostly do notexpress ER, PR and

9、 HER2, the two have overlapping,allexpressed cytokeratin (CKs5 / 6 and 17, but there are a small part of BLBC express HER2, so the two are not iden tical. TNBC on en docri ne therapy and is not sen sitive to anti-HER2 targeted therapy, chemotherapy, although effective, but because of early recurrene

10、e, rapid, short survival time and become the focus of atte nti on in rece nt years, this paper studies on the TNBC progress are reviewed.A molecular characteristicsNielse n and othermolecularfeatures by BLBC further study found thathormonereceptor and HER2 gene expression is usuallylow, and three n

11、egative as BLBC the main characteristics of studies have show n that about 85% of the TNBC is BLBC.Due to the current clinical breast cancer genetic testing techniques (standard test method for microarray gene profiling to carry out less, and immunohistochemistry tech no logy is gen erally carried o

12、ut, some scholars believe it may be TNBC equivale nt BLBC.BLBC that originated in the basal layer of the outer tube by myoepithelial cells, these cells express both epithelial cells and smooth muscle cell characteristics, expressionof high molecular weight basal cytokeratins(CKs such as CK5 / 6, CK1

13、4 and P53 protein CK17.BLBC expressi on can be up to 85%, and is usually accompa nied by P53 gene mutation.P53 proteinis a cell cycleregulatory protei n, whose role is toin hibitcellproliferati on, and to mon itor DNA damage and in duc ing cell differentiation and apoptosis, these functionswhenP53 m

14、utati on loss lead ing to tumorige nesis. BLBC higher rate of gen etic aberrati ons with features, and other types of breastcan cer compared to the more freque ntoccurre nee of cha nges in the nu mber of DNA replicati on, suggesti ng BLBC may have a greater degree of geno mic in stability.Recent stu

15、dies provide growing evidenee that BRCAI-related breast ca ncer with TNBC and BLBC greaterreleva nee,BRCAI-relatedbreastcan ceris duetomutatio nsin BRCA1 genelead toin stability,lead ingtobreast can cer. BRCA1 Themai nrole of mutationsbyhomologousrecomb in ati onrepairof double-strandedDNA, the lack

16、 of BRCA1 DNA repair process will result in error-pr on e, lead ing to gen etic in stability 5. BRCA1 gene mutatio nand in creased risk of breast can cer, 80 % ofhereditary breast cancer, the family discovered the gene mutation.BRCA1-related breast cancer and TNBC in theimmune phe no type and cli ni

17、 cal characteristics have many similarities, including ER-negative, Ki-67, EGFR, CK5 / 6 positive, P53 mutati on,highnu cleargrade, poorprog no sis.The study shows that BRCA1 breast can cer,TNBC and BLBC exists between the three more closely lin ked. BRCA1 mutatio n in breast can cer phe no types we

18、re located in the basal cell-like subsets, Tip two possible ways to have the same disease.2 pathological featuresTNBC has a variety ofhistological types, in cludi ngin vasive ductal carc inoma,in vasivelobular carc ino ma, medullarycarc inoma,muc inouscarc ino ma,tubularcarc ino ma,papillarycare ino

19、 ma, en docri necare ino ma,of which the morecom monin vasive ductal carc ino ma.TNBC histologicalgrade Compared with other types of breast cancer II - IDmore com mon, the primary tumor, the averagediameter of the larger, lymph no de-positive rate is slightly highertha nnon-triplen egative breast ca

20、n cer, innon-triplen egativebreastcan cerpatie ntswithno de-positive rate in creased with the in crease of tumor diameter, and threen egative breast can cer, eve n a smalltumordiameter,lymph node metastasis rate was alsohigher in tumors<1cm in patients with node-positiverate was 55%, while thecor

21、resp ondingnon-triple-negative breast can cer in only 19%.The majority of cases TNBC BLBC, morphological features of these BLBC main ly as follows: (1 pushing the edge of the tumor and surroundingtissueboundariesmore clearly, (2 cell-like tumor cells were fit,un clear boun daries,vary ingdegrees of

22、lymphocytein filtrati on, and medullary carc inoma of the tissue as close to (3 n ests of tumor cells, arran ged in sheets, the lack of duct-like structures,Can cerCen tershows that collage n-based scar, visible patter n n ecrosis, (4 more tha nthe histological grade II level and grade 山,mitotic com

23、 mon nu clear cytoplasm ratio in creases, (5 shows spin dle cells and squamous cell metaplasia 6.3 Cli ni cal features and prog no sisAccord ingto statistics, TNBC patie nts with breast can cer acco unting for about 12% -40%, studies have found, TNBC age of on set of breast can cer tha n other types

24、 of small (media n age was 54 years old and 60 years old, Hispanic and non-Hispa nic white wome n Hispa nic black wome n, a higher prevale nee of low socio-ec ono mic status of wome n have a higher prevale nee in Asia n coun tries, South Korea and Japa n, a lower in cide nee of wome n 7. TNBC patie

25、nts gen erally larger tumor diameter, lymph node metastasis rate, mass small lymph node metastases can occur a higher rate of soft tissue visceral metastasis and recurrenee rate, mainly involving the lungs, followed by the liver, while the low rate of bone metastasis 8.TNBC s 5-year survival rate is

26、 low, patients withdiffere ntcli ni calstages, in stage I , Irecurre nce-freesurvival and overall survival Ion ger tha nID patie nts, i n line with tumor stage affect the prog no sis of this conclusion. Survival analysis showed that lymph node status, tumor diameter, the expressi on of an droge n re

27、ceptor-positive disease-free survival and overall survival was negatively correlated, in which lymph node status, tumor diameter is an in depe ndentprog no sticfactor inTNBC. http:/www. .com 4 treatme nt4.1 Most cytotoxic drugs or TNBC patientswithBRCA1 deletion mutatio n, causi ng BRCA1-mediated DN

28、A repair the deficie ncies, so the drugtreatme ntofBRCA1-related tumors also for the treatmentof TNBC,such as alkylat ing age nt, mitomyci n C, plat inum drugs and etoposide, bleomyc in and so on.4.2 n eoadjuva nt chemotherapy studies suggestthat basal-like and HER2 (+)/ ER (- breast cancer,an thrac

29、ycli ne-c ontaining n eoadjuva nt chemotherapy tha n luminal breast can cer have higher efficie ncy. Rouzier and other studies have show n that basal-like breast can cer and HER2-type high expression relative to the luminal-type breast can cer patie nts and no rmal-like type breast can certype of pa

30、clitaxel and an thracycli nen eoadjuva ntchemotherapy better. reported that, TNBC patie nts compared to non-triplenegativebreast cancer patientshave a higher pathological completeremissionrate,pathological complete remissi on with non-TNBC patie ntscan be similar in patientswithtriplen egativebreast

31、can cer survival rate, whilestillin theresidualaftern eoadjuva ntchemotherapyincancerpatie nts,TNBCpatients compared to non-triplen egativebreastcancerprog no sis differe nee.4.3 metastaticreceptor-negativebreast cancerchemotherapyis curre ntlythreereportedTNBCchemotherapyforadvaneedopti onsare:plat

32、i nu m-co nta iningsolutions such asTC (paclitaxelandcarboplat in,programssuchasthenon-plati nu m-paclitaxelmono therapyor in comb in ati onwith capecitab ine or an thracycli nesand the rece ntlyreported FLN program (fluorouracil + foli nic acid + vin blasti ne coast, its efficie ncy at 46% -57%. FL

33、N program is received for the previous anthracycline or taxane and the metastatic TNBC more effective program.4.4 Targeted therapy TNBC lack ER and HER2 sig nali ngpathway abno rmalities of proliferati on,proliferati on drive n role in promot ing the proliferati on of these tumor cell proliferations

34、pecific mechanism is notentirely clear. EGFR overexpression is a feature of TNBC, up to 54% . EGFR inhibitors in unselected breast cancer treatme nt is in effective, but tak ing into acco unt about 54% of the TNBC patie nts express EGFR, therefore, if EGFR in hibitors comb ined with chemotherapy for

35、 TNBC may get good results, the curre nt releva nt reports have bee n. PARP (PARP1, PARP2 is a multifu nctio nal en zyme,whe nbreakage occurs when the single-strandDNA, PARP canrepair this damage, and in hibiti on of PARP can BRCA1 / 2 gene mutati ons in cell-selective apoptosis, because Most patie

36、nts with BRCA1 mutatio ns TNBC, PARP in hibitors may become a new treatmentfor TNBC. Dasatinib is an oralsmall molecule multi-target kin ase in hibitor, while the role of the src and ab1 protei n, part of the pre-cli nical results show that dasati nib sen sitivity of TNBC cells, its role in the trea

37、tment of TNBC is being investigated.angiogenesisin hibitor Avasti n is a recomb inant huma ni zed monoclonal10antibody with VEGF (vascular endothelialgrowth factorcompetitivecomb in ati onof VEGF receptors,block ingVEGF-mediated biological activity, therebyin hibit ingvascular endothelial cell mitos

38、is, reducing angiogenesis, in hibit tumor growth.TNBC is a high-risk breast can cer, because theoverallprog no sisis poor, high rate of lymph nodemetastasis, visceral metastasis and recurre nee rate of soft tissue, atte nti on has bee n paid in rece nt years gradually.TNBC has a special biological behavior and pathological features, and has a unique cli ni cal course. A comb in ati on ofexisti ngimmunedetecti onmethods help usunderstandthe TNBC, and its more in-depthstudy tobetter develop specific and effectivein dividualizedcomprehe nsive treatme nt pla n