A role for biomarkers in the screening and diagnosis of breast cancer in younger women

University of California, San Francisco, Department of Surgery, 1600 Divisadero Street, Box 1710, San Francisco, CA 94115, USA.
Expert Review of Molecular Diagnostics (Impact Factor: 3.52). 10/2007; 7(5):533-44. DOI: 10.1586/14737159.7.5.533
Source: PubMed


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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    • "Generally, cancer development may undergo the stages of benign proliferation (hyperplasia and low grade dysplasia), precancer (high grade dysplasia and carcinoma in situ) and cancer (invasive and metastatic carcinoma) [2] [3]. Breast cancer if detected early is curable by prevention or intervention of progression of precancer to invasive and metastatic types [4] [5]. Thus, specific biomarker (s) that are expressed in breast precancerous lesions [atypical hyperplasia and carcinoma in situ (CIS)] are required for the early detection of breast cancers. "
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    ABSTRACT: Piwil2, a member of AGO/PIWI family of proteins, has been reported to be expressed in precancerous stem cells (pCSCs), tumor cell lines and various types of human cancers. However, the significance of piwil2 expression in breast cancer has not been investigated. In this study, archival formalin-fixed, paraffin-embedded breast cancer specimens at various developmental stages were prepared as tissue microarrays (TMAs) and examined for the expressions of piwil2, estrogen receptor (ER), progesterone receptor (PR) and a cell proliferation marker Ki67 by immunohistochemical (IHC) staining and human epidermal growth factor receptor 2 (HER2) by fluorescence in situ hybridization (FISH). The correlation of piwil2 expression with ER, PR and Ki67 were analyzed statistically. The piwil2 was detected in all of breast cancer TMA cores. In contrast, ER, PR, HER2, and Ki67 were detected only in 66.1%, 54.5%, 36.0%, and 47% of the TMA cores, respectively. Piwil2 was expressed in cytoplasm (Cyt), nucleus (N) or both cytoplasm and nucleus (C-N). The N pattern was less observed in breast precancers, whereas all three patterns were observed in invasive and metastatic cancers. While the Cyt pattern was significantly correlated with ER expression (p = 0.002); N pattern was significantly correlated with Ki67 expression (p =0.001). ER and Ki67 expressions were reduced and increased, respectively, with the expression patterns being shifted from Cyt --> C-N --> N. In conclusion, piwil2 is expressed in various stages of breast cancers and has the potential to be used a novel biomarker.
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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
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