Molecular biomarkers of risk in premalignancy and breast cancer prevention.

About 50,000 U.S. women are diagnosed with breast atypical hyperplasia each year, giving them about a six-fold increased relative risk of developing invasive breast cancer (IBC) compared with age-matched controls. Still, only a small fraction of patients with atypical hyperplasia ever progress to IBC, which is a major reason why a large majority do not participate in breast cancer prevention, despite the remarkable effectiveness of currently available risk-reducing therapies. An interesting study reported by Radisky and colleagues in this issue of the journal (beginning on page 1953) evaluated expression levels of p16(ink4a) in atypical hyperplasia for more accurately predicting risk--hoping to identify high-risk patients who will benefit most from therapy while sparing those with lower risk from unnecessary therapy. Unfortunately, p16(ink4a) expression was not prognostic in this particular study, although research to identify powerful biomarkers of risk remains a high priority. Fortunately, there are many other promising biomarkers under investigation, as well as several underutilized experimental strategies which could help promote successful breast cancer prevention.