Currently available breast cancer screening tools such as mammography and breast examination miss up to 40% of early breast cancers, are least effective in detecting cancer in young women whose tumors are often more aggressive, and requires that an invasive needle or surgical biopsy be performed when an area of suspicion is identified to confirm the presence of malignancy. Our goal is to develop a noninvasive method to assist in the early detection of breast cancer or precancerous changes. The primary focus of this study is to detect promising markers in nipple aspirate fluid (NAF) by performing a comprehensive analysis of the proteins that are expressed (protenomics). SELDI (Surface Enhanced Laser Desorption/Ionization) mass spectrometry methods will be used for the analyses. We have compelling preliminary data using protenomic analysis of NAF that proteins of a given molecular weight can be identified which are highly expressed in women with breast cancer and are expressed little or not at all in women without disease. These analyses can be performed using one microliter of NAF. We wish to study women scheduled to undergo diagnostic breast biopsy. This population would be well served if we could determine whether someone has breast cancer without submitting them to an invasive procedure. Specifically, in the feasibility aspect of the study (R21 component, Phase I), we will: 1) determine the protein expression pattern in NAF among women with and without breast cancer using SELDI and 2) identify promising candidate markers in NAF that can be used in screening for the presence of breast cancer. We will establish quantifiable milestones which must be attained in order to proceed to further development of a predictive model among women scheduled to undergo breast biopsy. Specifically, in the second stage of the study (R33 component, Phase II), we will use the markers identified in Phase I, along with a number of other clinical measures, to predict the presence of both precancer and invasive breast cancer. In addition, we will accurately quantitate and identify the sequences of the proteins identified by SELDI and the majority of proteins present in NAF using tandem mass spectrometry (MS/MS) methods in combination with the use of isotope-coded affinity tags (ICATs) and microbore liquid chromatography/MS/MS. Our long term goal is to develop and validate the use of markers in NAF to noninvasively evaluate the breast for cancer, which we hope will serve as an adjunct to currently available methods of risk assessment and disease detection.
| Sauter, Edward R; Davis, Wade; Qin, Wenyi et al. (2009) Identification of a beta-casein-like peptide in breast nipple aspirate fluid that is associated with breast cancer. Biomark Med 3:577-88 |
