Analysis On Correlation Between Circulating Tumor Cells Of Breast Cancer And Molecular Biological Characteristics

Background:Breast cancer, in the early stage of which distant metastasis can befound, is a kind of malignant tumor with a high incidence currently.Postoperative recurrence and metastasis, which are mainly caused bycirculating tumor cells (CTCs) in the peripheral blood of patients, are twokey factors influencing the prognosis[1]. To find sensitive targets for earlydiagnosis and individualized treatment plan of breast cancer, manyinvestigations have been done at gene and molecular biological level.Although ER, PR, HER-2, Ki67and P53were the focuses in thoseinvestigations, they cannot be detected continuously in the course oftreatment (adjuvant treatment especially) but be detected only for primarytumor generally, due to which they cannot be used as the monitoringindices for the rapeutic effect. As the monitoring index for breast cancerin the peripheral blood, CTCs can be collected at any time for real-time"liquid biopsy", which is conducive to a better individualized treatment ofbreast cancer[2]. Thanks to the Cell Search System (a technique forCTCs detection and analysis) by which trace amount of CTCs can bedetected, a single CTC can be accurately detected among over400million blood cells just from a blood sample of7.5ml. Thus, throughanalyzing the correlation between the count of CTCs given by theCellSearch System and the clinical features of patients with invasivebreast cancer and the immunohistochemical indices of ER, PR, HER-2,Ki67and P53and the molecular subtypes of breast cancer, a combinedindex available for both early diagnosis and prognosis of breast cancerwas investigated. Objective:To acquire the count of CTCs of patients with invasive breast cancerby the CellSearch System and evaluate the correlation between CTCsand the clinical features and the molecular biological characteristics ofpatients with breast cancer at a certain base level.Methods：1.53patients with invasive breast cancer, who were diagnosed eitherby breast tumors core needle biopsy or by postoperative pathologicaldiagnosis in all the breast surgeries within Jilin province, were includedfrom December2011to December2013. Prior to some adjuvanttreatments such as chemotherapy and radiotherapy, the count of CTCs ofthe patients with invasive breast cancer was acquired by the CellSearch System and the base level was evaluated. The standards forcollection, storage and transportation of peripheral blood were madebefore detection.2. The expressions of ER, PR, HER-2, P53and Ki67of the patientswith invasive breast cancer were detected immunohistochemically.3.Based on the detection via the Cell Search System, the patientswere divided into2groups including a group in which there were21patients with a count of not less than5CTCs/7.5ml each and the othergroup in which there were32ones with a count of less than5CTCs/7.5ml each. Besides, the peripheral blood samples from10patients withbenign breast tumor were collected as control.4. The correlations between CTCs count, age of onset, family history,menopause, TNM staging and the patients either with breast cancermetastasizing in M stage or with recurrence were analyzed. And so werethe correlations between CTCs count and ER, PR, HER-2, Ki67and P53and the molecular subtypes of invasive breast cancer. Results：1. No CTCs were found in the10patients with breast fibro adenoma.There was no statistical difference between CTCs count and familyhistory and menopause of the patients with invasive breast cancer(P>0.05) while the difference in CTCs count between the group of onsetage≥60years and other groups was found (P <0.05).2. Significant correlation was found between CTCs count and TNMstaging, the CTCs count between each TNM stage was statisticallysignificant (P=0.01). The CTCs count of the patients with recurrent/metastatic breast cancer (stage Ⅳ/M1) was significantly higher(P=0.001) than that of the patients with operable breast cancer (stage, Ⅱ,Ⅲ, M0).3. There was no significant difference (P>0.05) in CTCs countamong the patients with different receptor statuses of ER, PR, HER-2andKi67, though weak correlation (P=0.075) was found between P53andCTCs count.4. There was significant difference (P=0.01) in CTCs count between3types of breast cancer including Luminal B type, TNBC type andLuminal A type.Conclusions：1. The Cell Search System with high specificity can be applied inthe treatment for the patients with recurrent or metastatic invasive breastcancer. Significant correlation was found between CTCs count and TNMstaging of breast cancer, which showed that the possibility of distantmetastasis significantly increased when CTCs≥5. Therefore, CTCs countcan be used independently to evaluate the tumor burden of breast cancer,which is important to precise staging and accurate assessment of patient’scondition as well as prognosis. 2. There was no significant correlation between CTCs count and ER,PR, HER-2, Ki67, P53of the patients. Weak correlation found betweenP53and CTCs count, which might show significance if a bigger samplesize is given, provides a combined index available for both diagnosis andprognosis of breast cancer.3. There was significant difference between CTCs count andLuminal types of breast cancer. Proliferation and invasion of Luminal Btype and TNBC type might be the important reasons for thehematogenous metastasis and the high detection rate of CTCs in thepatients with breast cancer of those types. CTCs in patients can directlyaffect the survival and the prognosis of the patients with differentmolecular subtypes of breast cancer.