Role of Cathepsin D in Monitoring Breast Cancer Treatment Using Doxorubicin in Combinations with Cyclophosphamide and 5-Fluorouracil

Background: Over-expression of cathepsin D by reactive stromal cells leads to an adverse clinical course in breast cancer. Its elevated level in breast cancer tissue is highly significant indicator of the potential for recurrence. Aim: To find out the role of Cathepsin D in monitoring breast cancer using Doxorubicin in combinations with Cyclophosphamide and 5-fluorouracil (FAC). Methods: Fifty female patients with breast cancer visited department of Oncology, Sir Ganga Ram Hospital and INMOL Hospital Lahore were selected in this study. Women with estrogen receptor positive breast cancer stage II and III and not received any radiotherapy as yet were included in the study. Estrogen receptor negative patients and Patients who have already received radiotherapy were excluded from the study. Patients are divided into two groups. Group -A including 50 Patients receiving Inj 5flourouracil 500mg/m(2) I/V Day 1 and Day 8. Inj Doxorubicin 50 mg/m(2) I/V Day1. Inj Cyclophosphamide 500mg/m(2) I/V Day1. Course is to be repeated every 21 days x 6 courses. A detailed proforma regarding brief history and examination was filled. In Group B, 20 normal subjects (controls) with no history of any disease were taken. Out of 50 females, 12 were menstruating, 18 were peri-menopausal and 20 were post menopausal. Level of cathepsin D was estimated in three stages. Before starting chemotherapy, in the middle of chemotherapy and at the end of chemotherapy. Cathepsin D was assessed by a standard kit method ("BioVision" company). Results: Level of cathepsin D in breast cancer women with different menstrual status was increased as compared to their controls. This showed highly significant difference (P<0.001). It was observed that the level of cathepsin D was high in menstruating women as compared to perimenopausal and postmenopausal women. In mid of treatment in women with different menstrual status, the levels of cathepsin D were significantly decreased (P<0.001) when compared with initial levels. At the end of treatment levels of cathepsin D were significantly decreased (P<0.001) when compared with initial and mid levels of cathepsin D. We observed that the reduction in the level of cathepsin D in menstruating women was 80.28% and at the end of treatment the reduction was 60.09%. Conclusion: It is concluded that cathepsin D is a good prognostic marker in receptor positive breast cancer women treated with FAC. However, there is a need of more efficacious adjuvant treatments for declining breast cancer mortality especially in developing countries.