RESUMO
BACKGROUND: Drug resistance remains as a challenge in the treatment of HER2-overexpressed breast cancer. Emerging evidence from clinical studies show relation of oxidized low density lipoprotein (LDL) and very low density lipoprotein (VLDL) level with drug resistance. However, the underlying molecular mechanisms for this effect remain unclear. Therefore, the aim of this study was to determine the effects of oxidized-LDL and VLDL in drug-resistant HER2-overexpressed breast cancer cells. METHODS: An in vitro cell model for tamoxifen-resistant HER2 overexpressed UACC732 cells was created using the pulse method. Cells were exposed to oxidized LDL (oxLDL) and very low density lipoprotein (VLDL) separately. Effects on cell morphology was studied using phase contrast microscopic changes. Percentage of cell viability was measured using proliferation assay kit. Development of tamoxifen resistance was determined based on P-gp expression with flow cytometry. Further analysis includedcell death measurement with flow cytometry method. RESULTS: UACC732 cells exposed to VLDL exhibited fibroblast-like morphology. This was further supported by proliferation assay, where the percentage of cell viability achieved more than 100% with 100 µg/ml of VLDL exposure, indicating cell proliferation. Findings also showed that VLDL caused reduction in expression of Pgp in resistant cells compared to resistant cells alone (p = 0.02). CONCLUSION: Results of this study suggest that VLDL may play a role in growth of drug-resistant HER2-overexpressing cells. Lower expression of P-gp in presence of VLDL need to be investigated further.
RESUMO
INTRODUCTION: Sabah, formerly known as North Borneo, is part of East Malaysia. 52.2 percent of patients with breast cancer in Sabah presented at advanced stages and up to 20.4 percent of patients defaulted proper treatment, opting for traditional therapy. We performed a two-year prospective study looking at the treatment trends of breast cancer in Sabah. METHODS: Our subjects were all newly-diagnosed breast cancer cases seen at the hospital in 2005 and 2006. Type of surgery, chemotherapy, radiotherapy, hormonal therapy and surgical complication for each patient were studied. RESULTS: Out of 186 newly-diagnosed cases, 152 (81.7 percent) had surgery, 126 (67.7 percent) had chemotherapy, 118 (63.4 percent) had radiotherapy and 92 (49.5 percent) had hormonal therapy. 18.3 percent did not have surgery either due to refusal of treatment or advanced disease. They were more likely to be non-Chinese (91.1 percent, p-value is 0.02). Only 15.8 percent had breast-conserving surgery. The most frequent surgical complication was seroma formation (15.0 percent) . The commonest chemotherapy regime and hormonal therapy were anthracycline-based regime (88.1 percent) and tamoxifen (95.8 percent), respectively. CONCLUSION: The proportion of breast-conserving surgery and usage of modern adjuvant therapies are low in Sabah. This can be attributed to lack of breast cancer awareness leading to late presentation and refusal of treatment, coupled with insufficient health service funding.
