new test to detect methylated DNA in blood plasma2 detect bc early/followtrtmenteffct

[Lani]

15 September 2006
Plasma biomarkers may reveal breast cancer
Epigenetic markers, such as methylated DNA sequences, may allow the detection of breast cancer without recourse to mammography, although the identification of further breast-cancer specific markers would be beneficial, argue US and Senegalese investigators.

Breast cancer remains the second leading cause of cancer mortality among women, despite a significant decline in death rates during the 1990s that resulted, at least partly, from early diagnosis by screening mammography.

However, mammography is not feasible in developing countries, making novel approaches to breast cancer screening necessary.

Nancy Kiviat, from the University of Washington in Seattle, and colleagues therefore examined the value of blood-based biomarkers. They studied plasma from 93 West African women with predominantly advanced breast cancer and 76 healthy controls using high through-put DNA methylation assay to determine the frequency of aberrant methylation in four candidate genes: APC, GSTP1, Rass1A, and RAR-beta-2.

Dividing the samples evenly into training and validation sets, the team found that the frequency of methylation in plasma DNA of APC, GSTP1, and Rass1A was significantly higher in patients than in controls, at 17% versus 0%, 26% versus 0%, and 32% versus 5%, respectively.

In contrast, the difference in methylation frequency between patients and controls for RAR-beta-2 did not reach statistical significance, at 26% versus 8%.

The methylation of at least one gene for identifying cancer cases had a sensitivity of 62% and a specificity of 87%, and eight of 24 (33%) early-stage cancers were detected using the test, the team reports.

They write: "The detection of occult circulating tumor cells using a combination of epigenetic markers may not only enhance insight into the biologic behavior of a primary tumor of an individual, but may also provide valuable prognostic information that can be easily monitored throughout the disease course."

The researchers add: "One could envision an expansion of the current panel to other relevant and specific tumor suppressor genes to increase the sensitivity of the assay that might... be particularly useful for the diagnosis of early-stage breast cancer."



J Clin Oncol 2006; 24: 4262-4269

http://www.jco.org/cgi/content/abstract/24/26/4262
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