Abstract
It is well established that mutations in the BRCA1 gene are a major risk factor for breast cancer. Induction of cancer cell death and inhibition of survival are the main principles of cancer therapy. In this context, autophagy may have dual roles in cancer, acting on the one hand as a tumor suppressor and on the other as a mechanism of cell survival that can promote the growth of established tumors. Therefore, understanding the role of autophagy in cancer treatment is critical. Moreover, defects in apoptosis, programmed cell death, may lead to increased resistance to chemotherapy. The aim of the present study was to detect BRCA1 gene mutations in order to throw more light on their roles as risk factors for breast cancer in Egypt. Secondly the role of autophagy and apoptosis in determining response to a fluorouracil, doxorubicin, cyclophosphamide (FAC) regimen was investigated. Forty-five female breast cancer cases and thirty apparently healthy females were enrolled in the present study. Serum levels of autophagic biomarkers, Beclin 1 and LC3 as well as the serum levels of apoptosis biomarkers Bcl-2 and Caspase-3 were measured before and after chemotherapy. BRCA1 mutations were found in 5 (16.7%) and 44 (99.8%) of the controls and cancer patients, the most frequent being 5382insC followed by C61G and 185 delAG. The results revealed that chemotherapy caused elevation in serum concentration levels of the autophagic biomarkers (Beclin 1 and LC3). This elevation was associated with a significant decrease in serum concentration levels of Bcl-2 and significant increase in caspase-3 concentration levels (apoptotic markers). The results of the present study indicate a very high level of BRCA mutations in breast cancer cases in Egypt and point to involvement of autophagic and apoptotic machinery activation in response to FAC chemotherapy.
Highlights
As the leading cause of cancer deaths among women breast cancer remains a medical and social challenge, as well as a major public health problem
Inclusion criteria: i) Patients pre-operatively clinically diagnosed as breast cancer patients by clinical mammography; ultrasound; Fine Needle Aspiration Cytology (FNAC) and breast biopsy. ii) Breast cancer patients with stage (II-III) and that were subjected to surgical treatment. iii) Breast cancer patients that did not receive pre-operative neoadjuvant chemotherapy. iv) Breast cancer patients that receive the recommended adjuvant chemotherapy course consists of six cycles of 5-Flourouracil, Adriamycin, and cyclophosphamide (FAC)
In respect to autophagy markers, serum Beclin 1 and LC3 concentration levels in breast cancer patients were significantly elevated after chemotherapy (Figure 4)
Summary
As the leading cause of cancer deaths among women breast cancer remains a medical and social challenge, as well as a major public health problem. Purpose: The aim of the present study was to detect BRCA1 gene mutations in order to throw more light on their roles as risk factors for breast cancer in Egypt. The results revealed that chemotherapy caused elevation in serum concentration levels of the autophagic biomarkers (Beclin 1 and LC3) This elevation was associated with a significant decrease in serum concentration levels of Bcl-2 and significant increase in caspase-3 concentration levels (apoptotic markers). Conclusions: The results of the present study indicate a very high level of BRCA mutations in breast cancer cases in Egypt and point to involvement of autophagic and apoptotic machinery activation in response to FAC chemotherapy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Asian Pacific journal of cancer prevention : APJCP
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
