الفهرس 
BREAST CANCEROnly 14 pages are availabe for public view
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Abstract
Worldwide, breast cancer is the most common malignancy in women. It is the second leading cause of cancer death in females, exceeded only by lung cancer, but it is the first in women under the age of 55. In Egypt, it accounts for 31% of all female cancers, and is responsible for 15% of cancer deaths in women .
Breast cancer is commonly diagnosed using clinical breast examination, mammography, and fine needle aspiration cytology referred to as “triple test”. The triple test is accurate and can replace open surgical biopsy for diagnosis when all three components are concordant; that is, all benign or all malignant. However, early-stage breast cancer typically produces no symptoms when the tumor is small and most treatable. It is therefore very important to detect breast cancer at an early stage, as this offers the best chance for its successful treatment.
The need for additional dignostic indicators to improve the identification of breast cancer patients has led to the use of a plethora of potential markers in the last ten years such as carcinoembryonic antigen (CEA), cancer antigen (CA) 15-3, and HER- 2. Unfortunately, the currently available markers for breast cancer lack sensitivity for early stage disease, precluding their use in both screening and diagnosing early breast cancer. Moreover, these markers show a low specificity, which is essential to protect patients with false positive results from unwarranted diagnostic evaluations. In addition, most available prognostic markers require tumor tissue. Consequently, it would be desirable to have a circulating marker for breast cancer which improves the identification of breast cancer patients and provides prognostic information.
Nectins -4 is a cellular adhesion molecule involved in Ca2+-independent cellular adhesion. It has been found that nectin-4 can be found in the serum of patients suffering from breast,ovarian and lung cancers. This has led to speculations that this protein might be involved in some developing cancers and might even have a pharmaceutical potential.
In this regard the present study aimed to evaluate the clinical utility of serum Nectin-4 in comparison to CA 15.3 and CEA in patients with breast cancer. The study was conducted on 80 female patients who presented to the surgery and oncology units of Ain Shams University Hospitals. The patients group was subdivided into 2 subgroups, 40 localized breast cancer patients ,and 40 breast cancer patients with distant metastasis. In addition, 20 healthy subjects were included as controls.
All patients included in this study were subjected to full medical history taking, clinical examination, routine investigations and post operative histopathological examinations of the tumors. Nectin-4 was measured by flow cytometer technique, CA 15.3 and CEA were measured by electrochemiluminescence immunoassay in both patients and control groups.
When breast cancer patients were compared to the control group, this revealed a non-significant difference between the two groups regarding CEA. However, CA 15.3 and Nectin-4 levels differs significantly between the two groups.
In addition the level of CA15.3 was significantly higher in breast cancer patients with distant metastasis compared to localized breast cancer patients. However, there was no statistically significant difference between the two Subgroups regarding Nectin-4 levels and CEA levels.
When breast cancer patients were classified according to tumor grade, the three studied markers showed no statistically significant difference between grade 2 and grade 3 breast cancer patients.
When breast cancer patients were classified according to tumor stage, the only statistical significant difference was recorded by CA15.3 between stage 2 and stage 4.CA15.3 also recorded a statistical significant difference between stage 3 and stage 4 patients. Nectin-4 recorded a statistical significant difference between stage 2 and stage 4 patients.
Correlation study between Nectin-4 and the other parameters in breast cancer patients showed a highly significant positive correlation between Nectin-4, CEA and CA15.3.
Although CA15.3 and CEA showed no statistically significant difference between estrogen and progesterone receptors positive and negative patients, Nectin-4 was statistically significant higher in estrogen receptors negative patients and progesterone receptors negative patients.
Regarding the diagnostic performance of Nectin-4 in discriminating breast cancer patients from the healthy control group , at a cut-off 0.02%, it had a diagnostic sensitivity of 80%, specificity 50%, negative predictive value 38.5%,positive predictive value 86.5%and efficacy 74% .
Regarding the diagnostic performance of CA15.3 in discriminating breast cancer patients from the healthy control group , at a cut-off 6 ng/mL , it had a diagnostic sensitivity of 90%, specificity 30%, negative predictive value 42.9%,positive predictive value 83.6%and efficacy 78% .
Regarding the diagnostic performance of CA15.3 in discriminating localized breast cancer patients from breast cancer patients with distant metastasis , at a cut-off 15 ng/mL , it had a diagnostic sensitivity of 65%, specificity 67.5%, negative predictive value 65.9%,positive predictive value 66.7%and efficacy 66.3% .
Combined use of either increased CA15.3 or Nectin-4 levels proved to have better diagnostic sensitivity than using individual markers separately or using both increased markers at the same time.