الفهرس 
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Abstract
Breast cancer (BC) is the most common malignancy among women worldwide and is one of the major contributors to the global death burden. Therefore, it is critical to discover prognostic factors as well as therapeutic targets for breast cancer. Recent epidemiological studies have demonstrated that obesity is associated with an increased risk for BC in women, although the mechanism by which obesity may play a part in the development of BC required clarification. Increased estrogen levels have been suggested as one possible explanation, but this does not fully explain the relationship between obesity and BC. One alternative explanation that has been proposed in the secretion by adipocytes of metabolites, hormones and cytokines collectively known as adipocytokines,which regulate the physiological and pathological processes. Of these, adipokines is adipocyte-fatty acid binding protein (A-FABP).
Aim of the work:
In the present study, we attempted to investigate whether A-FABP and omega 3: omega 6 ratio in serum of obese and non obese BC patients could be used as potential prognostic tools for BC taking into account clinicopathological features and anthropometric parameters.
Subjects and methods:
Sixty female patients who were newly diagnosed with BC (30 obese and 30 non obese) were enrolled into the study as patient groups. Thirty women with normal mammography findings and no previous history of any kind of cancer (15 obese and 15 non obese) with matched age and body mass index served as control group.
Clinical information regarding age, the menopausal status, weight and height of all participants was recorded. BMI was calculated as weight in Kgs divided by the square of height in meters.
The blood samples were collected within a week before surgery. All blood samples we obtained at fasting early in the morning and the serum was immediately separated by centrifugation and stored at -20° until use. Serum A-FABP levels were measured by enzyme linked Immunosorbent assay and Omega 3/Omega 6 ratio was assayed by the use of gas chromatography. Subjects were followed up clinically, radiologically and by laboratory testing for 30 months to assess the prognostic value of the markers.
Results and Discussion:
According to the results of the present study the mean values of A-FABP levels in serum of obese and non obese control subjects, were nearly within the same range and showed insignificant difference. Similar result was observed for the two groups of patients diagnosed with breast cancer. On the other hand, the mean values of that parameter in serum of non obese and obese breast cancer patients were significantly higher than their corresponding control values. According to these results, it seems reasonable to predict that adipocytes are not the main source of A-FABP and their high levels in serum of BC patients.The elevated levels of this parameter may be attributed to its expression and secretion from breast cancer cells and macrophages standing in cancerous tissue,which increase proinflammatory status of cancer
Additionally, statistical analyses of these results showed that there might be a close correlation between A-FABP and breast cancer risk. Based on these findings, the data seems to suggest a possibility that A-FABP levels could be a new risk factor for BC.
Also, the association of A-FABP with clinicopathological parameters of BC patients was evaluated. It was found that high concentration of A-FABP observed in obese and non obese patients group was significantly correlated with histopathological parameters and not with anthropometric measures of obesity (BMI). The effect was clearly seen in the association between A-FABP and tumor histological grade, clinical stage, tumor size, axillary lymph node involvement, ER and PR negativity and Her/2neu positivity, already tested as prognostic markers. In view of these results, it was predicted that alteration of this parameter may affect cell proliferation, tumor invasion and angiogenesis. Thus metastasis of tumor cells is more likely to develop under the high A-FABP condition. This study clearly indicates that serum A-FABP could be an interestingand promising biomarker for BC, independently of (BMI).
Furthermore, the statistical analyses of the results showed that the mean values of omega 3 : omega 6 ratio showed insignificant difference either between obese and non obese control groups or between obese and non obese BC patients. On the other hand, the mean values of omega 3 : omega 6 ratio in both obese and non obese BC patients were significantly lower than their corresponding control values. Of interest, the present study also found that Omega 3: omega 6 ratio in obese and non obese BC groups was negatively significantly correlated with tumor size, BMI and serum A-FABP and not with age, histological grade, clinical stage, ER and PR status and Her/2neu expression. This result suggests that differences in breast cancer incidence rates may be related, in part, to intake of dietary fat. Omega 6 polyunsaturated fatty acids may stimulate both mammary tumor growth and metastasis, whereas omega-3 PUFAs may have a tumor-inhibiting effect. Moreover,omega-3 polyunsaturated fatty acids significantly repressed the basal A-FABP expression and abolished induction of A-FABP expression.
In the present study, it was found that the relationship between serum A-FABP and prognosis was analyzed by evaluating DFS in total group of 60 female patients. The analyses of DFS showed that the higher level of this parameter is significantly associated with poor prognosis in patients with primary BC. The log rank of A-FABP was (8.21). This log rank value indicated that the possibility of metastasis or local recurrence in BC patients with A-FABP levels above its cut off value (8.5 ng/ml) waseight timesfold than in BC female with A-FABP levels below its cut off value during 30 months of follow up. This study supports the finding that serum A-FABP levels may add prognostic information to that obtained from classical prognostic factors.
The preoperative levels of serum Omega 3: omega 6 ratio failed to predict survival or metastasis in primary BC patients. Therefore, we can predict that serum Omega 3: omega 6 ratio cannot be used for monitoring the response to chemotherapy and surveillance.