الفهرس 
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Abstract
Breast cancer remains an important public health problem for women all over the world. Breast cancer is considered a systemic disease because micrometastases may be present even in patients with small tumors at early stages. Despite considerable advances in the diagnosis and treatment of solid tumors, distant metastases remain the principal cause of death.
Since multiple bone marrow aspirations from the same patient during follow-up are not easily tolerated, the peripheral blood would be a more convenient source of sampling for such longitudinal follow-up studies.
Circulating tumor cells (CTCs) are rare malignant cells found in the peripheral blood that originate from the primary tumor or metastatic sites.These cells may represent the tumor population that is most likely to develop metastases. The presence of these cells was described through identification of tumor like cells in the peripheral blood of cancer patients.
Detection of circulating tumor cells in the circulation can provide prognostic as well as therapeutic information and help in identifying patients at high risk for developing metastases.
MUC1 and mammaglobin are two molecules that are specifically associ¬ated with breast cancer. In the present study looked for mammaglobin and MUC1 transcripts in the peripheral blood of patients with breast cancer and evaluated their utility as a marker of the response to therapy.
The aim of this study was to detect the expression of circulating tumor cells in blood of breast cancer females as a prognostic marker for breast cancer.
This study included 57 premenopausal females divided into 2 groups: the first group included 25 healthy females and the second group included 32 females with recently detected breast cancer of clinical stages II and III who received FAC as adjuvant chemotherapy after surgery.
Patients were followed up from the start of the research. Three blood samples were drawning: before surgery, after two weeks of surgery and after six cycles of chemotherapy. A forth blood sample was with drawn during a median follow up of 24 months from patients who developed metastasis. In all blood samples, MUC1 and mammaglobin transcripts were analyzed by RT-PCR and level of CA15-3 was evaluated in serum by ELISA.
This study revealed that, none of 25 healthy individual blood samples were positive mRNA expression for either MUC1 or h-MAM whereas, MUC1 transcript was detected in 28 (87.5%) of 32 patients before surgery, 29 (90.6%) of 32 patients after 2 weeks of surgery and 20 (62.5%) of 32 patients after 6 cycles of chemotherapy.
Mammaglobin transcript was positive in 87.5% of breast cancer patients at diagnosis. Furthermore, the detection of h-MAM mRNA expression in blood samples of breast cancer patients after 2 weeks of surgery was (56.3%) and after adjuvant chemotherapy (46.9%). It could then become a surrogate marker for micrometastatic spread and early indicator of disease progression.
Regarding to serum CA15-3, its median level was 14.3 U/ml for all breast cancer patients before surgery. This indicates that it is not a suitable marker for diagnosis of breast cancer. After 2 weeks of surgery there was a non statistically significant decrease in its level (11U/ml).Its median value showed non statistically significant increase after 6 cycles of chemotherapy (17.5U/ml).
After a median follow up of 24 months, disease progression was observed in 16/32 (50%) of breast cancer patients who displayed MUC1 and h-MAM mRNA positive expression. Regarding to serum CA15-3, its level was markedly elevated in the metastatic patients.
After a median follow up of 24 months, we classified our malignant group into metastatic and non-metastatic groups and we found that the percent of positive axillary lymph nodes was significantly higher in metastatic group (66.7%) than non-metastatic (33.3%) (p=.002). Also, we observed that the percent of the presence of vascular invasion was significantly higher among metastatic than non-metastatic group (p=.001).
We did not gain from the combination of the markers even when we combined the best performing markers at different times .By consequence, we can more or less suggest that there is no need to combine markers ,unless widely proven otherwise.