Breast Hyperplasias, Risk Signature, and Breast Cancer

Abstract

We address the dilemma faced by oncologists in administering preventative measures to "at risk" patients diagnosed with atypical and nonatypical hyperplasias due to lack of any molecular means of risk stratification and identifying high-risk subjects. Our study purpose is to investigate a four marker risk signature, MMP-1, CEACAM6, HYAL1, and HEC1, using 440 hyperplastic tissues for identifying high-risk subjects who will benefit from preventative therapies. We assayed the markers by IHC 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 nonatypical subjects, respectively. We have established a correlation between risk scores and cancer rates by stratifying the samples into low risk (score 0.5); intermediate risk (score 5.4), and high risk (score >5.4) groups using Kaplan-Meier survival analysis. We have evaluated cancer rates at 5, 10, and 15 years. Our results show that the average cancer rates in the first 5 years among low-and intermediate-risk groups were 2% and 15%, respectively. Among highrisk group, the average cancer rates at 5 years were 73% and 34% for atypical and nonatypical subjects, respectively. The molecular risk stratification described here assesses a patient's tumor biology-based risk level as low, intermediate, or high and for making informed treatment decisions. The outcomes of our study in conjunction with the available prophylactic measures could prevent approximately 20%-25% of sporadic breast cancers.

Stromal lymphocytes are associated with upgrade of B3 breast lesions

“…Many efforts to identify predictive biomarkers of upgraded B3 lesions have failed because of either a lack of sensitivity: the “low risk” group still has a considerable risk of upgrade [ 33 ], the predictive feature is not reproducible [ 34 , 35 ] or the feature is only prognostic after full excision [ 32 , 36 ]. Overall, predictive features are inconsistent across studies and many of the features require highly experienced pathologists and radiologists to interpret the available data.…”

Utility of stromal lymphocytes in diagnosis and predicting upgrade of B3 breast lesions from core biopsies

“…Many efforts to identify predictive biomarkers of upgraded B3 lesions have failed because of either a lack of specificity: the “low risk” group still has a considerable risk of upgrade [29], the predictive feature is not reproducible [30, 31] or the feature is only prognostic after full excision [28, 32]. Overall, predictive features are inconsistent across studies and many of the features require highly experienced pathologists and radiologists to interpret the available data.…”