CPB 69700 RESEARCH SEMINAR

 

DEPARTMENT OF COMPARATIVE PATHOBIOLOGY

 

Munazzah Rahman, MS

Graduate Student in Cancer Research

Purdue University

 

Thurs., April 16, 2009

VPTH 112  -  3:30 pm

 

Metabolomic Analysis of Aggressive

Breast Cancer in African American Women” 

 

Abstract: 

Breast cancer continues to remain the second leading cause of cancer deaths despite increased awareness, early detection and implementation of adjuvant hormonal and chemo-therapies.  This is partly due to the disparity in mortality rates among women of diverse racial and ethnic groups. Age-adjusted mortality rates have been higher among African American women and the divergence is even more pronounced in pre-menopausal women, wherein African American women have a 77% higher mortality rate than Caucasian American women (11.0 versus 6.3 deaths per 100,000).

African American women also tend to present with more aggressive forms of breast cancer which is characterized by higher pathological grade, greater lymph node involvement, and later stage at diagnosis. All of which contribute towards poorer prognosis and worse survival even after controlling for stage at diagnosis. The purpose of this project is to determine the metabolome profile of aggressive, basal-like Estrogen Receptor-negative breast tumor in premenopausal African American women and compare it to that of race-, age- and stage-matched Estrogen Receptor-positive breast cancer.

Methods: Subsequent to IRB approval and patient consent, histopathologically confirmed frozen, invasive, Stage III Adenocarcinoma (estrogen receptor positive, N=20 and negative, N=20) will be collected from premenopausal (<50), newly diagnosed patients that are registered at Indiana University and Clarian Arnett Health.  Patient history (food, alcohol, smoking, and medications) will be obtained.  Exclusion criteria would be prior chemotherapy.

The tissue will be derivatized and subjected to Metabolomic Analysis via a global analytical device (Nuclear Magnetic Resonance, and Gas Chromatography coupled with Mass Spectrometry). The metabolomic process functions by identifying and quantifying metabolomes in a biological matrix.  Metabolomes are the endogenously synthesized, low molecular weight, end product molecules of gene expression, post-transcriptional, post-translational activities and various other biochemical pathways. Therefore, they tend to amplify any alterations that occur due to dysfunction. The multivariate data procured from the process will be scrutinized via software programs that identify patterns and trends of interest and provide a metabolomic phenotype

Significance:  Examining the metabolome variability may provide valuable insights into potential functionally significant variations. It will also provide markers for diagnosis and molecular targets for therapy.

Future Direction:  Subsequent studies will determine the presence of the validated biomarkers in the plasma and will lead to the development of an easy diagnostic screening modality specifically designed for African American women.