A role for biomarkers in the screening and diagnosis of breast cancer in younger women
The widespread usage of screening mammography has resulted in an increase in the detection of early-stage disease, particularly in situ (stage 0) and early-stage (stage 1) cancers. However, incidence of stage 2 and 3 disease has not fallen commensurately, suggesting a bias in the detection of indolent cancers rather than aggressive cancers. Improved screening and diagnosis of a broader range of cancers is therefore an important need. Although MRI is a very sensitive breast cancer detection tool that has become standard for women at very high risk, it lacks sufficient specificity and cost-effectiveness for use as a general screen. The greatest opportunity for molecular tools to improve breast cancer outcomes is to better discern biologically aggressive cancers, especially in women under the age of 50 years. In this age group, presentation in stage 2 or 3 is more common and mammographic screening is less efficacious. We propose a multi-tiered triage strategy that uses emerging markers of susceptibility to segment the population for more focused screening with imaging. In particular, it would be helpful to identify a subset of at-risk, younger women who would benefit from intensive surveillance or preventive interventions. It is likely that tests for susceptibility, unless they are highly specific, will need to be combined with indicators of short-term risk. Although the combined sensitivity and specificity of screening must be high, each individual test does not require high specificity. It is important, however, for the susceptibility tests and short-term risk markers to be highly sensitive. If the majority of women under 50 years of age who develop breast cancer are captured with this strategy, then mammography screening for the general population can start at age 50 years. Finally, and perhaps most importantly, biomarkers of susceptibility and short-term risk are likely to provide insight into the biology of tumors that develop, leading to new interventions to support prevention. The most effective preventive strategies will be those where a marker predicts risk for the disease, as well as the benefit from preventive interventions.
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