HER2 Support Group Forums - View Single Post - Circulating Tumor DNA Detects Metastatic Breast Cancer

gdpawel · 03-14-2013, 12:09 AM

I think the most difficult markers to validate are panels in which a SNP (single nucleotide polymorphism) array or microarray of tumor DNA or RNA are assessed and the goal is to come up with a multifactor signature to predict responsiveness.

Researchers have been focusing on the development of sensitive assays that allow the specific detection of single tumor cells or small amounts of cell-free tumor DNA in the peripheral blood of cancer patients (Annual Review of Medicine Vol. 63: 199-215). Quantification of circulating DNA by real-time PCR may be a good and simple tool for detection of cancer with a potential to clinical applicability together with other current methods used for monitoring the disease (DNA Cell Biol. 2008 Aug;27(8):415-21).

Doctors hope to use this to assess how a patient's tumor responds to treatment. Circulating tumor DNA might give doctors an earlier warning that a drug isn't working. The test might allow patients to stop taking a harsh drug that's not working, sparing them months of side effects. Doctors could then prescribe an alternative drug, although there's no evidence yet that switching drugs sooner would help people live longer.

Is this six of one and a half dozen of the other? The test is "prognostic" and not "predictive."

The biggest point made by Dr. Eric Winer, director of the breast oncology center at Boston's Dana-Farber Cancer Institute, is that cancer patients shouldn't expect their doctors to test their tumor's circulating DNA anytime soon.

Genomics provides a new type of very specific biomarker for monitoring tumors in response to therapy. The mutations that each tumor accumulates are an individual genomic 'barcode' that can then be used to monitor tumor burden and response to treatment.

The researchers use targeted or whole-genome sequencing to identify somatic genomic alterations and design a personalized assay to quantify circulating tumor DNA in serially collected plasma specimens. The also measure CA 15-3 levels and numbers of circulating tumor cells at identical time points.

Circulating tumor DNA was successfully detected in 29 of 30 women (97%) with metastatic breast cancer receiving systemic therapy in whom somatic genomic alterations were identified. In comparison, CA 15-3 was detected in 21 or 27 women (78%) and circulating tumor cells were detected in 26 of 30 women (87%).

Circulating tumor DNA has a greater dynamic range, which correlates with changes in tumor burden. The test also can provide the earliest measure of treatment response in 10 of 30 women tested.

Most laboratories equipped to do molecular testing can do this test using circulating tumor DNA, however, these are usually only located in major tertiary care centers.

The editorialists pointed out that all patients with breast cancer have mutations in their tumor DNA, but without very intensive sequencing strategies, a specific probe or probes for each patient may remain elusive or very costly, and a standard 'panel' is unlikely to work for all patients.

The number of patients in whom an objective response to treatment was seen in circulating tumor DNA was limited, so the effort to compare the usefulness of circulating tumor DNA with circulating tumor cells and measures of CA 15-3 is more encouraging than definitive.

03-14-2013, 12:09 AM	#2
gdpawel Senior Member Join Date: Aug 2006 Location: Pennsylvania Posts: 1,080	Free-floating DNA from tumor could provide early warning? I think the most difficult markers to validate are panels in which a SNP (single nucleotide polymorphism) array or microarray of tumor DNA or RNA are assessed and the goal is to come up with a multifactor signature to predict responsiveness. Researchers have been focusing on the development of sensitive assays that allow the specific detection of single tumor cells or small amounts of cell-free tumor DNA in the peripheral blood of cancer patients (Annual Review of Medicine Vol. 63: 199-215). Quantification of circulating DNA by real-time PCR may be a good and simple tool for detection of cancer with a potential to clinical applicability together with other current methods used for monitoring the disease (DNA Cell Biol. 2008 Aug;27(8):415-21). Doctors hope to use this to assess how a patient's tumor responds to treatment. Circulating tumor DNA might give doctors an earlier warning that a drug isn't working. The test might allow patients to stop taking a harsh drug that's not working, sparing them months of side effects. Doctors could then prescribe an alternative drug, although there's no evidence yet that switching drugs sooner would help people live longer. Is this six of one and a half dozen of the other? The test is "prognostic" and not "predictive." The biggest point made by Dr. Eric Winer, director of the breast oncology center at Boston's Dana-Farber Cancer Institute, is that cancer patients shouldn't expect their doctors to test their tumor's circulating DNA anytime soon. Genomics provides a new type of very specific biomarker for monitoring tumors in response to therapy. The mutations that each tumor accumulates are an individual genomic 'barcode' that can then be used to monitor tumor burden and response to treatment. The researchers use targeted or whole-genome sequencing to identify somatic genomic alterations and design a personalized assay to quantify circulating tumor DNA in serially collected plasma specimens. The also measure CA 15-3 levels and numbers of circulating tumor cells at identical time points. Circulating tumor DNA was successfully detected in 29 of 30 women (97%) with metastatic breast cancer receiving systemic therapy in whom somatic genomic alterations were identified. In comparison, CA 15-3 was detected in 21 or 27 women (78%) and circulating tumor cells were detected in 26 of 30 women (87%). Circulating tumor DNA has a greater dynamic range, which correlates with changes in tumor burden. The test also can provide the earliest measure of treatment response in 10 of 30 women tested. Most laboratories equipped to do molecular testing can do this test using circulating tumor DNA, however, these are usually only located in major tertiary care centers. The editorialists pointed out that all patients with breast cancer have mutations in their tumor DNA, but without very intensive sequencing strategies, a specific probe or probes for each patient may remain elusive or very costly, and a standard 'panel' is unlikely to work for all patients. The number of patients in whom an objective response to treatment was seen in circulating tumor DNA was limited, so the effort to compare the usefulness of circulating tumor DNA with circulating tumor cells and measures of CA 15-3 is more encouraging than definitive.