Molecular Analysis of Nipple Fluid for Breast Cancer Screening

Abstract

Lack of sensitivity and specificity of image-based breast cancer screening has urged the exploration of alternate screening modalities. Nipple fluid, which contains breast epithelial cells, is produced in small amounts in the breast ducts of nonlactating women and can be collected by noninvasive vacuum aspiration. After administration of nasal oxytocin, nipple aspiration yields sufficient material for molecular analysis in the large majority of women. Whereas nipple fluid cytology appears to have only a moderate correlation with breast cancer development, methylation holds promise as a more appropriate biomarker, since methylation aberrations occur as an early and frequent event during carcinogenesis. Using quantitative multiplex methylation-specific PCR, methylation can be detected in minute amounts of DNA extracted from nipple aspirates, precluding the need for more invasive intraductal approaches such as ductal lavage and random periareolar fine needle aspiration. The application of genomic and proteomic diagnostics to nipple aspirates therefore provides unprecedented opportunities for early breast cancer diagnosis amendable to population-based screening.

Novel Methylated Biomarkers and a Robust Assay to Detect Circulating Tumor DNA in Metastatic Breast Cancer

“…The cMethDNA assay is a refinement of the QM-MSP method used extensively by our laboratory and others (6, 7, 9, 10, 14). Here, a low fixed physiological level of recombinant gene-specific standard reference DNA is introduced into a constant volume of serum (50 copies of gene-specific standard in 300 μl serum) prior to purification of the DNA.…”

Clinical significance of promoter hypermethylation of DNA repair genes in tumor and serum DNA in invasive ductal breast carcinoma patients

“…Methylated genes were identified in body fluids (Taback et al 2006;Euhus et al 2007;Suijkerbuijk et al 2008) and serum (Fiegl et al 2005;Mirza et al 2007;Sharma et al 2007) of breast cancer patients. However, much work remains to be done to prove unequivocally which methylated CpG islands are important in breast cancer, to definitively establish the relationship between epigenetic changes in tumor and serum and to demonstrate a tumor type-specific pattern (Costello et al 2000).…”

Successful oxytocin-assisted nipple aspiration in women at increased risk for breast cancer

“…A screening method that gives access to the tissue in which breast cancer arises could add value to the existing methods and increase the rate of breast cancer detection at an early stage [4]. Nipple Aspirate Fluid (NAF), containing breast epithelial cells, free DNA, secreted proteins and hormones is produced in the breast ducts of non-lactating women.…”