Circulating tumor cells are cells that break off from a cancer tumor and move into the blood stream. Doctors sometimes test for circulating tumor cells to see if breast cancer cells are active in areas of the body beyond the breast. The number of circulating tumor cells also affects a cancer's prognosis. Right now, finding 5 or more circulating breast cancer tumor cells in 7.5 milliliters (ml) of blood suggests a worse prognosis, and finding fewer than 5 circulating tumor cells suggests a better prognosis.
The study reviewed here used a mathematical model to analyze how higher levels of circulating tumor cells affected the prognosis of people diagnosed with breast cancer. The model suggests that the more circulating tumor cells in the blood sample, the greater the person's risk of dying from breast cancer. Some day, doctors may be able to better estimate a person's prognosis based on the specific number of circulating breast cancer tumor cells rather than looking at only whether there are more or less than 5 cells in a blood sample.
The link between higher numbers of circulating tumor cells and worse prognosis was found in various types of breast cancer:
Still, the link between circulating tumor cells and prognosis was stronger in breast cancers with certain characteristics. The link was the strongest in estrogen-receptor-positive, HER2-positive breast cancers. The link was the weakest in triple-negative breast cancers (estrogen-receptor-negative, progesterone-receptor-negative, and HER2-negative).
While these results are interesting, more research is needed before doctors use specific numbers of circulating breast cancer tumor cells to help make treatment decisions.
Stay tuned to Breastcancer.org's Research News to learn more about lab research that may lead to better ways to diagnose and treat breast cancer.
BRUSSELS (MedPage Today) -- Greater numbers of circulating tumor cells predict worse metastatic breast cancer prognosis without a threshold, researchers reported here.
Sophisticated statistical analysis showed a linear increase in mortality with incrementally higher numbers of circulating tumor cells across hormone receptor and HER2 receptor status groups, according to Antonio Giordano, MD, of the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues.
The researchers discussed their findings here at the IMPAKT Breast Cancer Conference.
In women with hormone receptor-positive, HER2-positive metastatic breast cancer for example, the hazard ratio for death rose with the number of these cells per 7.5 ml blood (compared to none), as follows:
These results suggest that the conventional threshold of five such cells per 7.5 ml of peripheral blood "probably does not adequately represent the complexity of this prognostic variable," the researchers concluded.
Still, Giordano did not recommend abolishing the current cutoff based on the results a single study, even though it involved a more powerful statistical analysis that controlled for more covarying factors than previous work.
Thresholds can be useful in making treatment decisions, he acknowledged in an interview. However, he said, the continuous nature of the risk found in the study may open up opportunities for more accurate prognosis at the individual patient level, determining how aggressively to treat.
Conference co-chair Angelo Di Leo, MD, PhD, of the Hospital of Prato, Italy, called the findings important, given the clear heterogeneity among metastatic breast cancers.
"The big hope is that with these new tools -- including circulating tumor cells -- we can better characterize from a biological point of view metastatic breast cancer," Di Leo said at a press conference.
He likewise agreed that this would give clinicians an advantage in determining the duration and most effective treatment.
However, it possible that simply looking at the DNA or other circulating markers might be better than trying to isolate viable cells with a short half-life, commented John Bartlett, PhD, of the Edinburgh Cancer Research Centre in Edinburgh, Scotland, who was the study discussant at the IMPAKT session.
Most centers don't have access to the sort of "Artificial Neural Network" that the authors used for computing in the study, but Giordano said he envisioned it as an online resource which physicians could use to calculate risk for a patient by entering 10 patient characteristics.
The threshold for determining high versus low risk with regard to circulating tumor cells has been debated -- with some researchers thinking about an any-versus-none threshold and others suggesting a plateau above 10 or 15 cells, Giordano explained in an interview.
These cells are seen as a measure of tumor burden, he noted.
His group retrospectively analyzed outcomes for 516 consecutive metastatic breast patients evaluated at M.D. Anderson, all of whom had circulating tumor cells measured by Cell Search before any line of new treatment was started.
The "neural network" assessed the following variables in conjunction with overall survival over a median 11.7 months of follow-up:
The statistical model "trained" using 60% of the patients' predicted survival probabilities matching the Kaplan-Maier estimates for the remaining 40% in the validation set.
The hazard ratios with rising numbers of circulating tumor cells was highest for the estrogen receptor-positive, HER2-positive tumors (up to almost eight-fold), followed by estrogen receptor-negative, HER2-positive tumors, and then estrogen receptor-positive, HER2-negative tumors and triple negative cancers.
All these histologically-defined molecular subtypes showed the same pattern of linear increase in mortality risk with rising numbers of circulating tumor cells.
The researchers reported no external funding and no conflicts of interest.
Bartlett and Di Leo reported no conflicts of interest.
Primary source: IMPAKT Breast Cancer Conference Source reference: Giordano A, et al "Circulating Tumor Cells (ctc) and Artificial Neural Network (ANN) in Metastatic Breast Cancer (MBC) Patients" IMPAKT 2010; Abstract 25O.
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