Effect of treatment with chemotherapy alone or in combination with an anti-inflammatory drug on some angiogenic factors in breast cancer patients

الملخص EN

Breast cancer is a major health problem.

In Alexandria, Egypt, in the last ten years, breast cancer constituted 33 % of all cancers The aim of this study was to investigate the effect of treatment with 5-fluorouracil (5-FU), Doxorubicin (adriamycin), and cyclophosphamide (FAC) on two angiogenic parameters, vascular endothelial growth factor and epidermal growth factor, and to study the role of sulindac (Anti-cyclooxygenase) (COX) when combined to the chemotherapy.

This study included 60 females, divided into three groups.

The first group included 25 females with recently detected breast cancer of clinical stage II who received 6 cycles of FAC as adjuvant chemotherapy after surgery.

The second group comprised 25 females of similar clinical stage to group I, they received sulindac (400 mg / day) by oral administration, together with the same regimen of chemotherapy given to group I.

The third group, included ten healthy females matched in age and menstrual status with the patients (control group).

Patients were followed up to six cycles and blood samples were drawn before surgery, after two weeks of surgery (before starting chemotherapy), after 3 and 6 cycles of treatment with FAC alone or in combination with sulindac.

Serum vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) were mentioned in each blood sample drawn.

This study revealed that the levels of serum VEGF and EGF were significantly increased in all studied groups (I, II) when compared to their corresponding control values.

VEGF serum level was significantly elevated after 6 cycles of treatment in patients treated with FAC alone, while EGF level decreased by the end of the treatment course, compared to their corresponding values before treatment.

The levels of VEGF and EGF showed significant association with different histopathological parameters.

Both parameters were associated with lymph node status, which suggest that VEGF and EGF may play a role in lymphangiogenesis, and maybe considered as novel predictive factors for lymph node metastasis.

Disease free survival analysis, revealed a decrease in relapse probability in patients receiving FAC in combination with sulindac (group II), than those receiving FAC alone (group I), however ; this difference was not significant, a possible reason could be a small sample size.

The dramatic decrease in VEGF and EGF in patients receiving FAC in combination with sulindac, compared to their corresponding values before starting the treatment, could be explained on the basis of the action of sulindac in increasing the chemosensitivity of cancer cells and inducing their apoptosis.

From the results obtained in the present study, it could be concluded that breast cancer is associated with elevated VEGF and EGF, which contributes to a more aggressive disease and poorer prognosis.

This suggests the importance of using drugs that interferes with production and signaling of VEGF and EGF, which could lead to inhibition, at least in part, of tumor angiogenesis and to reduce the risk of recurrence in the postsurgical FAC-treated breast cancer patients by lowering VEGF and EGF levels.