Poola I, et al. - In order to develop a tool to detect high-risk patients diagnosed with atypical and nonatypical hyperplasias who will benefit from preventative therapies, researchers sought to discover a four marker risk signature, MMP-1, CEACAM6, HYAL1, and HEC1. They used 440 hyperplastic tissues. A “Cancer Risk Score” comprising a composite value from 0–10 was obtained by assaying the markers via IHC and combining their expression levels. Subsequent cancer development was predicted with an accuracy of 91% for atypical subjects and 86% for nonatypical subjects by using the four marker-based risk scores. In the first 5 years, the average cancer rates were 2% and 15% among low- and intermediate-risk groups, respectively. At 5 years, the average cancer rates were 73% for atypical subjects and 34% for nonatypical subjects among the high-risk group. With the proposed molecular risk stratification, informed treatment decisions can be made and a patient's tumor biology–based risk level can be evaluated as low, intermediate, or high. Nearly 20%–25% of sporadic breast cancers could be avoided considering the outcomes of this investigation combined with the available prophylactic measures.