The role of BRCA1 in sporadic breast and ovarian cancers remains elusive. Direct involvement of BRCA1 in the development of breast and ovarian cancer is suggested by the finding that the BRCA1 promoter region CpG island is methylated in a proportion of breast and ovarian cancers. The aim of this study was to compare the incidence of BRCA1 promoter region methylation in tumours in which loss of BRCA1 has been shown to play a role in pathogenesis (breast and ovarian carcinomas) with the incidence in tumours in which BRCA1 is unlikely to play a role in pathogenesis. Promoter region hypermethylation was significantly more common (P < 0.008) in breast and ovarian cancer (6/38 tumours methylated) than in colon cancer (0/35 tumours methylated) or in leukaemias (0/19 samples methylated). The restriction of BRCA1 promoter region hypermethylation to breast and ovarian cancer is consistent with a pathogenetic role of BRCA1 promoter methylation in these tumours. We suggest that the rarity of observed BRCA1 mutations in sporadic breast and ovarian cancer is due to the greater likelihood of BRCA1 inactivation by non-mutational mechanisms such as methylation.
Based on the National Breast Cancer Audit of the Royal Australasian College of Surgeons an association between patient age and type of breast cancer surgery received has already been demonstrated. The aim of this study is to assess the patterns of surgical treatment for women with early breast cancer in relation to socioeconomic and insurance status. Data on patient demographics, diagnostic, and surgical procedures and cancer characteristics in 115,872 episodes of early breast cancer reported to the National Breast Cancer Audit between 1998 and 2012 is used for this study. Tumor size, histologic grade, number of tumors, lymph node positivity, and lymphovascular invasion are the major prognostic factors adjusted for. Reconstruction following mastectomy is the most likely surgical procedure for the higher socioeconomic and privately insured patients. Mastectomy alone is the most likely surgical procedure for the lower socioeconomic and for public patients. No surgery is the most likely surgical outcome for the lower socioeconomic and the least likely for the higher socioeconomic population. Open biopsy is the most likely diagnostic procedure for the lower socioeconomic and fine needle aspiration for the higher socioeconomic population. Socioeconomic and insurance status, are both independently associated with the types of treatment and diagnostic procedure for women with breast cancer. Opportunities present to investigate an association of these factors with morbidity and survival outcomes.
Survivals appear to be increasing and treatment trends are broadly consistent with guideline directions, and the earlier research on which these recommendations were based.
BackgroundImmunomagnetic enrichment followed by RT-PCR (immunobead RT-PCR) is an efficient methodology to identify disseminated carcinoma cells in the blood and bone marrow. The RT-PCR assays must be both specific for the tumor cells and sufficiently sensitive to enable detection of single tumor cells. We have developed a method to test RT-PCR assays for any cancer. This has been investigated using a panel of RT-PCR markers suitable for the detection of breast cancer cells.MethodsIn the assay, a single cell line-derived tumor cell is added to 100 peripheral blood mononuclear cells (PBMNCs) after which mRNA is isolated and reverse transcribed for RT-PCR analysis. PBMNCs without added tumor cells are used as specificity controls. The previously studied markers epidermal growth factor receptor (EGFR), mammaglobin 1 (MGB1), epithelial cell adhesion molecule (EpCAM/TACSTD1), mucin 1 (MUC1), carcinoembryonic antigen (CEA) were tested. Two new epithelial-specific markers ELF3 and EphB4 were also tested.ResultsMUC1 was unsuitable as strong amplification was detected in 100 cell PBMNC controls. Expression of ELF3, EphB4, EpCAM, EGFR, CEA and MGB1 was found to be both specific for the tumor cell, as demonstrated by the absence of a signal in most 100 cell PBMNC controls, and sensitive enough to detect a single tumor cell in 100 PBMNCs using a single round of RT-PCR.ConclusionsELF3, EphB4, EpCAM, EGFR, CEA and MGB1 are appropriate RT-PCR markers for use in a marker panel to detect disseminated breast cancer cells after immunomagnetic enrichment.
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