Predicting how far cancer will spread is crucial in determining patients’ treatment, as metastasis points to a deadly progression. Now new research is challenging common diagnostic practices.

A cancer diagnosis is upsetting in its implications and in its uncertainty. How serious is it? How likely is it to spread? Tests currently available can predict tumor growth with some degree of accuracy, but a new study suggests that intravital imaging is a far more effective way to identify metastasis in the most common type of breast cancer.

Researchers at the Albert Einstein Cancer Center of Albert Einstein College of Medicine of Yeshiva University and Montefiore Einstein Center for Cancer Care used microscopy technology to count the number of sites in tumor specimens where cancer cells were prone to attack blood vessels; this helped the researchers better predict the risk of metastasis. A more precise prognosis means a better course of treatment for the cancer patient.

“Tests assessing metastatic risk can help doctors identify which patients should receive aggressive therapy and which patients should be spared,” said Thomas Rohan, M.D., Ph.D., the lead and corresponding author of the study and professor and chair of epidemiology and population health at Einstein and Montefiore.

The research was published in the Journal of the National Cancer Institute.

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By using intravital imaging to view the biological processes within tumors, researchers were able to observe how cancerous cells spread in breast cancer biopsy specimens.

The study was built upon previous research (conducted on rodents) at Einstein that demonstrated how the presence of three specific cells in the same site spurs the metastasis of breast cancer. This meeting point, called a tumor microenvironment of metastasis, or TMEM, is the location where tumor cells can enter blood vessels. Researchers developed a test using intravital imaging to identify these locations and predict the spread of cancer cells.

Tests such as the IHC4, which was used as comparison in the study, measure the levels of certain proteins in breast tumor tissue to determine metastastic risk, but the researchers require more information than what’s uncovered by this measurement.

“Current tests reflect tumor growth, rather than the intrinsic propensity of a tumor to spread,” explained Rohan.

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Breast cancer in particular was studied because of its universality and because of the prior research leading to this discovery.

“Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women worldwide,” Rohan said. “Initial work on multiphoton intravital imaging was done in animal models of mammary cancer development, and we are translating this into a test for predicting risk of metastasis in women with breast cancer.”

Researchers used their test on more than 500 breast cancer specimens collected over a 20-year period. The specimens were taken from women who developed distant metastasis and those who did not (as controls).

Researchers found that the TMEM test was successful at assessing the metastatic risk for the most populous cancer subgroup in the study. When compared with the IHC4 test, TMEM results were highly statistically significant, beating the former’s results, which were deemed borderline significant at best. This gives researchers reason to believe that TMEM testing provides more information than ICH4 testing.

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Intravital imaging is already helping doctors determine the intensity of treatment that cancer patients should receive, especially to prevent overtreatment in cancer’s early stages. Now researchers are exploring other options for the technology. In terms of breast cancer, intravital imaging is being used to assess metastastic risk with MRI-based prognostics. The researchers already have preliminary evidence that could be used in predicting the risk of metastasis in lung cancer, and they envision this methodology being applied to cancer in other body parts.

TMEM assembly is also a subject of further investigation. Preventing the formation of these lethal cell junctions would mean attacking cancer close to its source. The molecular operations involved in the formation and function of TMEMs has been identified in mouse models, and human trials will test TMEM-inhibiting drugs in breast cancer patients.

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