A role for biomarkers in the screening and diagnosis of breast cancer in younger women.
ABSTRACT 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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ABSTRACT: Breast cancer is the most frequently diagnosed cancer among Turkish women and both the incidence and associated mortality appear to be increasing. Of particular concern is the percentage of young women diagnosed with breast cancer; roughly 20% of all breast cancer diagnoses in Turkey are in women younger than 40 years. Increased DNA methylation in the promoter region of tumor suppressor genes is a promising molecular biomarker, and human milk provides exfoliated breast epithelial cells appropriate for DNA methylation analyses. Comparisons between DNA methylation patterns in epithelial (epithelial-enriched) and nonepithelial (epithelial-depleted) cell fractions from breast milk have not been reported previously.Journal of Human Lactation 08/2014; 30(4). DOI:10.1177/0890334414548224 · 1.98 Impact Factor
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ABSTRACT: Although mammography can reduce breast cancer mortality rates in screened populations, its modest sensitivity, especially in younger women with strong family histories for breast cancer, has prompted the introduction of breast magnetic resonance imaging (MRI) for high-risk screening. Seven prospective screening trials for high-risk patients in which MRI has been added to mammography indicate the sensitivity of MRI to be twice that of mammography alone. The specificity of MRI is lower than mammography in most, but not all studies; however, the specificity of MRI improves to a level comparable to mammography in screenings subsequent to the initial prevalence screen. Although the target populations in breast MRI screening studies have been identified by genetic and familial risks, the superior sensitivity of MRI has been demonstrated at all levels of elevated risk, raising the possibility that MRI screening could benefit women with risk factors other than a positive family history. The published studies on breast MRI screening are reviewed herein, along with new screening guidelines that are currently shaping practice patterns.Seminars in Breast Disease 06/2008; 11(2):67-75. DOI:10.1053/j.sembd.2008.03.002