Biography
Biography: Indira Poola
Abstract
Numerous clinical studies have established that diagnosis of hyperplastic masses
increases the cancer risk by 2-5 fold. Clinical follow-up surveys have shown that ~20%
and 10% of subjects diagnosed with atypical and non-atypical hyperpalsias respectively
develop cancer subsequently and are the most suitable candidates for preventative therapies.
However, there are no methods for identifying the above high risk subjects who will most
likely develop future cancers and benefit from prophylactic measures. Due to lack of any
risk stratification tools, healthcare providers as well as patients are faced with a dilemma in
undertaking preventative measures. Our study purpose is to investigate a four marker risk
signature, MMP-1, CEACAM6, HYAL1 and HEC1, using 440 hyperplastic tissues with up
to 19 years of clinical follow-up information for risk stratification and identifying high risk
subjects who will benefit from preventative therapies. We have assayed the marker levels in
the hyperplasia tissues and combined their expression levels to obtain a composite value
from 0-10 which we called a ‘Cancer Risk Score’. We demonstrate that the four marker
based risk scores predict subsequent cancer development with an accuracy of 91% and
86% for atypical and non-atypical subjects respectively. We have established a correlation
between risk scores and cancer rates at 5 years, 10 years and beyond by stratifying the
samples into Low (Score < 0.5), Intermediate (Score <= 5.4) and High (Score > 5.4) risk
groups and Kaplan Meier survival analysis. Our results show that the cancer rates in the
first five years among the low-, and intermediate risk groups were 2%, and 15% respectively
among atypical as well as non-atypical subjects. In the high risk group, the cancer rates
were 73% and 34% for atypical and non-atypical subjects respectively. The molecular risk
stratification developed by us assesses a patient’s tumor biology based risk level in terms of
a cancer risk score and categorizes the patient as low-, intermediate- or high risk for making
informed treatment decisions (Figure 1). The outcomes of our study in conjunction with
the already available prophylactic measures could prevent ~20%-25% of sporadic breast
cancers (Grant Support: National Cancer Institute, National Institutes of Health (CA173919
and CA206774) and the National Science Foundation (IIP-1314287) awarded to I. Poola)..