Abstract
Detection of breast cancer at an early stage is the key for successful treatment and improvement of outcome. However the limitations of mammography are well recognized, especially for those women with premenopausal breast cancer. Novel approaches to breast cancer screening are necessary, especially in the developing world where mammography is not feasible. In this study, we examined the promoter methylation of six genes (SFN, P16, hMLH1, HOXD13, PCDHGB7 and RASSF1a) in circulating free DNA (cfDNA) extracted from serum. We used a high-throughput DNA methylation assay (MethyLight) to examine serum from 749 cases including breast cancer patients, patients with benign breast diseases and healthy women. The six-gene methylation panel test achieved 79.6% and 82.4% sensitivity with a specificity of 72.4% and 78.1% in diagnosis of breast cancer when compared with healthy and benign disease controls, respectively. Moreover, the methylation panel positive group showed significant differences in the following independent variables: (a) involvement of family history of tumors; (b) a low proliferative index, ki-67; (c) high ratios in luminal subtypes. Additionally the panel also complemented some breast cancer cases which were neglected by mammography or ultrasound. These data suggest that epigenetic markers in serum have potential for diagnosis of breast cancer.
Highlights
Breast cancer is a complex and heterogeneous disease and one of the leading causes of death among women
We examined the promoter methylation of six genes (SFN, P16, hMLH1, HOXD13, PCDHGB7 and RASSF1a) in circulating free DNA extracted from serum
We assessed the promoter methylation of an six-gene panel (SFN, P16, hMLH1, HOXD13, PCDHGB7 and RASSF1a) in serum samples by using MethyLight, to investigate whether it could be used for diagnosis of breast cancer or not
Summary
Breast cancer is a complex and heterogeneous disease and one of the leading causes of death among women. Detection of breast cancer at an early stage is the key for successful treatment and improvement of outcome. A significant decline in breast cancer mortality between 1992 and 1996 is believed to be due, in part, to early diagnosis by screening mammography, the limitations of mammography [1] are well recognized, especially for those women with premenopausal breast cancer. The extensive laboratory and clinical infrastructure required for mammographic screening, as well as the high cost of mammography precludes such an approach. Given that the majority of women in many developing countries are under the age of 40 years, the problem of detecting premenopausal breast cancer is of particular important in such settings. Developing novel approaches for the early diagnosis of breast cancer has important clinical implications
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