Proteomic approach to breast cancer

Proteomic studies can clarify the heterogeneity of breast cancer and expand on advances gained from genomics research.

A royal lady admiring her youthful beauty. Kangra miniature, circa 18th century. Reproduced by the courtesy of the Bharat Kala Bhavan, Banaras Hindu University.

Proteomic Approach to Breast Cancer
Christine Laronga, MD, FACS, and Richard R. Drake, PhD
Background: Breastcancer is the most common cancer affecting women worldwide. Despite tremendous advances in screening, diagnosis, and treatment, the causes of this disease remain elusive and complex. Proteomics is a rapidly developing field that can explore the heterogeneity of breast cancer and supplement the wealth of information gained from genomics. Methods: This article serves as an overview of the applicationof matrix-assisted laser desorption/ionization source with a time-of-flight (MALDI-TOF) proteomic techniques as applied to breast cancer. Examples of the clinical applicability of MALDI-TOF mass spectrometry are provided but represent only a fraction of the potential uses yet to be discovered. In addition, a brief summary of the bioinformatics issues that surround proteomics is included. Results:Mass spectrometry has provided new proteomic approaches to unravel the complexities of clinical specimens relevant to breast cancer diagnostics. In particular, MALDI-TOF mass spectrometry analysis has been used to differentiate cancer profiles from benign profiles in samples from sera, plasma, tissue, nipple fluid, and ductal lavage. Some discriminating proteins have subsequently been identified.Conclusions: Mass spectrometry applications to breast cancer diagnostics continue to be developed but are evolving faster than bioinformatics/statistical analysis can adapt. The future of these techniques in terms of clinical investigation is limitless, but in terms of general applicability, these applications are currently cost-prohibitive.

From the Department of Surgery (CL), and theDepartment of Microbiology and Molecular Cell Biology (RRD) at the Eastern Virginia Medical School, Norfolk, Virginia. Submitted February 20, 2007; accepted June 29, 2007. Address correspondence to Christine Laronga, MD, FACS, Comprehensive Breast Program, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, MCC-BRPROG, Tampa, FL 33612. E-mail: Christine.Laronga@moffitt.org Nosignificant relationship exists between the authors and the companies/organizations whose products or services may be referenced in this article.
360 Cancer Control

The editor of Cancer Control, John Horton, MB, ChB, FACP, has nothing to disclose. Dr Laronga is now with the Comprehensive Breast Program at the H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida. Abbreviations used inthis paper: MALDI-TOF = matrix-assisted laser desorption/ionization source with a time-of-flight, SELDI = surface-enhanced laser desorption/ionization, MS = mass spectrometry, WCX = weak cation exchange.

October 2007, Vol. 14, No. 4

Introduction
Breast cancer remains one of the leading cancers diagnosed in women worldwide. Great strides have been made over the last 20 years in early detectionand treatment of breast cancer as evidenced by the earlier stage distribution at diagnosis and improved overall survival. With increased awareness and public education, screening mammography according to recommended guidelines is achieved in 65% to 70% of the US population.1 Computer-assisted detection (CAD) and digital imaging have been pioneered in the last few years to improve cancer detectionon mammograms by the radiologist. Additionally, technical advances in breast ultrasonography and breast MRI provide physicians with a full armamentarium of supplemental diagnostic imaging modalities for earlier detection of abnormalities found on clinical breast examination or mammography. Once an abnormality is identified, a tissue biopsy is performed that traditionally involved a surgical...