Preliminary Study Of The Changes In Circulating Tumor Cells Before And After The Core Needle Biopsy And Open Surgical Excision Biopsy For Breast Cancer

Early diagnosis of breast cancer is one of the priorities of the clinical work. Ourprevious study found that over the age of40women glands local thickening of theboundary is unclear and does not change with the menstrual cycle，Ultrasound and X-raylaboratory examinations suggest that breast density, structural changes or fine particles ofcalcification may be clinical manifestations of early breast cancer. But there is certaindifficulties in direct diagnosis of atypical hyperplasia, which is precancerous lesions of thebreast, by clinical and imaging studies。People whose Ultrasound and X-ray laboratory ofthe breast as BI-RADS3and the clinical manifestations is breast thickening，by the way ofCore needle biopsy to investigate the method that how to improve the detection rate ofprecancerous lesions and early breast cancer. This essay would focus on people who hadColor Doppler Ultrasound check and whose X-ray laboratory of the breast check isBI-RADS3and clinical manifestations is breast thickening, Core needle biopsy is adoptedin this study to investigate how to improve the detection rate of precancerous lesions andearly breast cancer. In the same way, carry our research on Clinicopathologic and moleculartyping in epithelia hyperplasia， epithelia atypical hyperplasia（ADH），ductal carcinomain situ (DCIS) and DCIS with microinvasive lesions of breast to explore the possibility ofbreast cancer precancerous lesions clinical monitoring. Core needle biopsy or open surgicalexcision biopsy for histopathological are common methods of breast cancer diagnosis, thisarticle, by detecting peripheral blood circulating tumor cells (CTC)， to research whether toincrease the risk of blood metastasis in the diagnosis of breast cancer by core needle biopsyor open surgical excision biopsy to research if open surgical excision biopsy or core needlebiopsy would increase the risk of blood metastasis。. Methods&ResultsPart Ⅰ. The clinical application of core needle biopsy (CNB)in diagnosis ofmastopathy without obvious mass.Methods: From may,2011to Dec,2011,891patients were enrolled in the study:1)withbreast pain and mass(asymmetrical mass or patchy glands thickening in unilateral breast),2)BI-RADS0-3,3) no improvement was found after treatment with Tamoxifen or Chineseformulated products. They all accepted CNB. The clinical manifestation in palpation andhistopathologic changes were investigated, and patients diagnosed with atypical hyperplasiawere followed up.Results891patients had CNB check,5patients was diagnosed as invasive ductalcarcinoma,6patients was intraductal carcinoma,1patient was malignant lymphoma,35patients were atypical ductal hyperplasia, and the rest was adenosis of breast. Among these35patients with atypical ductal hyperplasia,22patients accepted operation.11case werediagnosed as invasive ductal carcinoma,5patients was introductal carcinoma and6patientswas adenosis and atypical ductal hyperplasia.7patients refused operation and remained in thefollowing up.Part Ⅱ The clinical application of ER, PR, HER-2and WT1expresses in thegenerating and development of breast cancerMethods: There were95specimens that had confirmed diagnosed by pathology.【22cases of epithelia hyperplasia，23of epithelia atypical hyperplasia（ADH），23of ductalcarcinoma in situ (DCIS)，27of DCIS with microinvasive lesions】,Histopathology is got todetect the expressions of ER，PR，HER-2and WT1in the epithelia hyperplasia，ADH，DCISand DCIS with microinvasive lesions，and to investigate their variation and the possiblemechanism in the generating and development of breast cancer.Results The positive expression rates of ER in epithelia hyperplasia，ADH，DCIS，DCISwith microinvasive lesions were63.6％、73.9％、65.2％and51.9％（p＝0.445）. The positiveexpression rates of PR respectively are59.09％、69.57％、60.87％and44.44％（p＝0.336）.Itpositive expression levels and trends are the same with ER，It prompts us that the expressionlevels of ER，PR are increasing in the early stage of the breast cancer. The positive expressionrates are highest in ADH. Form the process of DCIS to DCIS with microinvasive lesions，Thepositive expression rates decline obviously, but the differences have no significance；The positive expression rates of HER-2respectively are4.55％、21.74％、60.87％�'�62.96％，it shows that in the process from ADH to DCIS，it increases significantly（p＜0.001）；Thepositive expression rates of WT1are31.82％、56.52％、13.0％、22.2％，The positiveexpression rates are highest in ADH.，declining obviously in the process of developing toDCIS，and gradually increasing to the process of invasive ductal carcinoma，the difference hasstatistical significance（P＝0.002）.Part Ⅲ. Decreased the diffierence of circulating tumor cells pre-and postoperativein core needle biopsy(CNB) and open surgical excision biopsy for breast cancerMethods: There are54patients in the group (39patients accept core needle biopsy；15patients accept open surgical excision biopsy).They are all women with breast cancer surgery.Pre-and postoperative (half to one hour after surgery) peripheral blood samples10ml， arecollected before core needle biopsy and open surgical excision biopsy and after core needlebiopsy and half hour after open surgical excision biopsy by density gradient centrifugation formononuclear cells and then detected by quantitative real-time reverse transcription-PCR(qPCR) for cytokeratin19mRNA-positive CTC. The difference in detection rate, medianlevels expressed as MCF-7cell equivalents/2μg RNA of CK19mRNA-positive CTC,micrometastatic risk from core needle biopsy(CNB) and open surgical excision biopsy werecompared and analyzed.Results: There was no significant difference in clinicopathologic characteristics betweenthese two groups. In the core needle biopsy(CNB) group，the positive rate of CTC before andafter biopsy were31%(12/39)、26%(10/39)(P=0.615)， the median levels of CK19mRNA-positive CTC expressed as MCF-7cell equivalents/2μg RNA before and after biopsywere0.18(0-5.46)and0.69(0.31-5.34)(P=0.658). Before and after core needle biopsy(CNB),the difference of positive rate and numbers of CTC has no significant meaning；In the opensurgical excision biopsy group，the positive rate of CTC before and after biopsy were13%(2/15)、33%(5/15)(P=0.39)，the median levels of CK19mRNA-positive CTC expressedas MCF-7cell equivalents/2μg RNA before and after biopsy were0.07(0-3.68) and0.61(0-2.32)(P=0.041).The number of CTC increases after biopsy in patients who acceptopen surgical excision biopsy，the difference has significant meaning(P=0.041)，butdifference of positive rate of CTC has no statistical significant meaning (P=0.39). Conclusions1. For patients with asymmetrical mass or patchy glands thickening in unilateral breast,although malignancy was not found in imaging examination, emphasis should be put on thelocal physical sign and the outcome post treatment. CNB was advised in those patients withno obvious improvement after drug treatment to exclude breast cancer or precancerosis. Forpatients with ordinary hyperplasia, he the main aim was to relieve clinical manifestation andconcern. And for patients with precancerosis, effective treatment and frequent follow-up wereactively recommended.2. In the process of breast cancer，[epithelia hyperplasia， epithelia atypical hyperplasia（ADH），ductal carcinoma in situ（DCIS) and DCIS with microinvasive lesions of breast]The current breast cancer molecular typing indicators include ER、PR and HER-2. Theirvariation in the previous stage of breast cancer needs further study. WT1may play anoncogene role in breast cancer development process.3. Core needle biopsy does not result in the shedding of tumor cells into the blood tocause iatrogenic micrometastases，but open surgical excision biopsy of the tumor cells shedinto the blood to be increased than core needle biopsy. While open surgical excision biopsyhas an increased influence on tumor cells shedding into blood than core needle biopsy does.