الفهرس 
Introduction
Breast cancerOnly 14 pages are availabe for public view
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Abstract
This study was conducted on 40 newly diagnosed breast cancer patients, aged 35-70 years. They were classified according to TNM staging system into 3 (stage I), 17 (stage II), 13 (stage III) and 7 (stage IV). The study also included 20 patients with benign breast lesions, of which; 11 patients with fibroadenoma, 4patients with lipoma, 2 patients with benign proliferative breast diseases, 1 patient with intraductal papilloma, 1 patient with granulomatous mastitis and 1 patient with periductal mastitis with fibrosis. All patients were recruited from General Surgery Department, Assiut University Hospital and Surgical Oncology Department, South Egypt Cancer Institute, Assiut University. The study also included 15 age matched apparently healthy individuals who were selected as a control group for comparison and 20 female individuals with risk factors for breast cancer development mainly family history (first degree relatives). Practical work was carried out at Clinical Pathology Department, Assiut University Hospital. All participants were subjected to the following: Full medical history. Full clinical examination.The following investigations were done for patients only as appropriately indicated:Chest x-ray. Abdominal ultrasound. Breast ultrasound or mammography. Histopathological examination of breast mass specimens (Tru cut or fine needle aspiration cytology). MRI and Bone scan. Laboratory investigations for all participants: Routine laboratory investigations: Hematological investigations: - Complete blood count (CBC). - Prothrombin time, concentration & international normalization ratio (INR). Chemical investigations: - Random serum glucose. - Kidney function tests. - Liver function tests. - Calcium. Special laboratory investigations: - Serum carcinoembryonic antigen (CEA). - Serum cancer antigen 15-3 (CA 15-3). Both were done by chemiluminescence immunoassay. - Plasma miR-27a by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The current study showed the following findings: BC biomarkers among the studied groups: Regarding CEA: There was no statistical significant difference of serum CEA levels in high risk group compared to control group. There was also no statistical significant difference of serum CEA levels in patients with benign breast lesions compared to high risk group. There was statistically significant elevation of serum CEA levels in breast cancer patients compared to control group, high risk group and patients with benign breast lesions. Also there was statistically significant elevation of serum CEA levels in patients with benign breast lesions compared to control group. Regarding CA15-3: There was no statistical significant difference of serum CA 15-3 levels in high risk group compared to control group. There were statistically significant elevation of serum CA 15-3 levels in breast cancer patients compared to control group, high risk group and patients with benign breast lesions. Also there was statistically significant elevation of serum CA 15-3 levels in patients with benign breast lesions compared to both control and high risk group. Regarding miR-27a: There was no statistical significant difference of serum miR-27alevels in high risk group compared to control group. Also there was no statistical significant difference of serum miR-27alevels in benign group compared to both control group and high risk group. There was statistically significant elevation of serum miR-27alevels in breast cancer patients compared to control group, high risk group and in patients with benign breast lesions. Relation of BC biomarkers to TNM stages: In the present study plasma miR-27a levels showed a statistically significant positive association with the TNM stages of BC. Plasma miR-27a was significantly higher in late BC (TNM stages III & IV) compared to early BC (TNM stages I & II) with (P-value < 0.05) for each. There was also statistically significant elevation of serum CEA and CA 15-3 levels in patients with late BC compared to early BC. Diagnostic performance of BC biomarkers for malignant cases (Control, High risk group, Benign cases VS malignant Cases): In this study, we constructed ROC curve for diagnosis of BC vs. healthy controls, high risk group and benign cases. Plasma miR-27a was 100% sensitive and 80% specific, with AUC of 0.983. These results are better than that of serum CEA, which was 87.5% sensitive and 87 % specific, with AUC of 0.943 and that of serum CA 15-3, which was 85% sensitive and 89% specific, with AUC of 0.955. Diagnostic performance of BC biomarkers (Early BC vs. Control): In order to early detect BC, we constructed ROC curve for diagnosis of early BC (TNM stages I & II) vs. healthy controls. Plasma miR-27a was 95% sensitive and 100% specific, with AUC of 0.993. Serum CEA was 75% sensitive and 100% specific, with AUC of 0.952. Serum CA 15-3 was 85% sensitive and 100% specific, with AUC of 1.0. Diagnostic performance of BC biomarkers (BC vs. benign cases): Also, we constructed ROC curve for diagnosis of BC vs. patients with benign breast lesions. Plasma miR-27a was 98% sensitive and 80% specific, with AUC of 0.969. These results were better than that of Serum CEA, which was 87.5% sensitive and 70% specific, with AUC of 0.905 and that of serum CA 15-3, which was 85% sensitive and 70% specific, with AUC of 0.878. In conclusion miR-27a detected by Real time PCR provides a non invasive method that can be useful in diagnosis and early detection of breast cancer. It could be satisfactory molecular biomarker for the prognosis of breast cancer. Measuring miR-27a at the time of diagnosis and during treatment can be useful in improving prognosis and survival rates. Conclusionfrom the present study, we concluded: 1. Plasma miR-27a level was significantly elevated in breast cancer patients compared to patients with benign breast lesions, females at high risk for breast cancer and healthy controls. 2. Measuring miR-27a in peripheral blood is a promising novel approach for diagnosis and early detection of breast cancer that has the advantages of being convenient, non-invasive and it may provide new diagnostic information. 3. Plasma miR-27a was significantly elevated in late breast cancer patients compared to early breast cancer patients, so they could be satisfactory molecular biomarkers in the prognosis of breast cancer. 4. No statistically significant difference in miR-27a level in patients with benign breast lesions and females at high risk for developing breast cancer compared to healthy controls. 5. Plasma miR-27a level had potential value for discrimination of malignant cases from non malignant cases (patients with benign breast lesions, females at high risk for developing breast cancer and healthy controls) and it had better diagnostic performance than serum CEA and CA 15-3. from the present study, we recommend: Plasma miR-27a may serve as non-invasive molecular biomarkers for early diagnosis of breast cancer. Follow up of patients with risk factors for breast cancer (e.g. family history of breast cancer) by serial measuring plasma miR-27a for early detection of breast cancer. The patient’s number is a potential limitation of our study. Further studies with larger number of patients will offer more detailed knowledge about the diagnostic role of plasma miR-27a in breast cancer diagnosis. Follow up study for breast cancer patients during and after treatment by plasma miR-27a to evaluate efficacy of the therapeutic interventions and detect recurrence. Perform miRNA profile analysis in whole plasma samples from breast cancer patients to discover more dependable microRNAs markers for diagnosis. Furthermore, studies should be carried out targeting microRNAs as an anticancer gene therapy.