A new bio marker for breast cancer metastasis called Tumor Microenvironment of Metastasis (TMEM) has been found by researchers at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

The density of TMEM was found to be associated with the development of distant organ metastasis via the bloodstream, the most common cause of death from breast cancer. The discovery was published in the journal Clinical Cancer Research March 24, 2009 online edition.

The study may result in the first test to predict the likelihood of breast cancer metastasis via the bloodstream. This is a development that has the possibility of changing the way breast cancer is treated.

“Currently, anyone with a breast cancer diagnosis fears the worst – that the cancer will spread and threaten their lives. A tissue test for metastatic risk could alleviate those worries, and prevent toxic and costly measures like radiation and chemotherapy,"

said senior author Dr. Joan G. Jones, professor at Weill Cornell Medical College.

It is estimated that 40 percent of breast cancer patients relapse and develop metastatic disease. Around 40,000 women die of metastatic breast cancer per year.

Better Targeting of Treatment

“If patients can be better classified as either low risk or high risk for metastasis, therapies can be custom tailored to patients, preventing over-treatment or under-treatment of the disease,"

adds author Dr. Brian D. Robinson, of NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

Investigators started out by building on earlier research by co-author Dr. John S. Condeelis of the Albert Einstein College of Medicine. Working with animal models, he recognized a link between blood-borne or systemic metastasis, and a three-part relationship between invasive perivascular white blood cells (macrophages), carcinoma cells, and the endothelial cells which line vessel walls.

For confirming this in humans, Drs. Jones and Robinson developed a triple immunostain for human breast cancer samples that simultaneously labels the three cell types that together they named TMEM (Tumor Microenvironment of Metastasis).

In the case-control study, they did an analysis of tissue samples from 30 patients having invasive ductal carcinoma of the breast who also developed systemic, distant-organ metastases. The samples were then compared to matched controls that had carcinoma limited to the breast only. All patients were female and had undergone primary resection of their breast cancer at NewYork-Presbyterian Hospital/Weill Cornell Medical Center between 1992 and 2003.

They revealed that TMEM was over twice as dense in the group of patients who developed systemic metastases, when compared with the patients with only localized breast cancer (median of 105 vs. 50, respectively). Offering further evidence in support of the TMEM concept, they found that in well-differentiated tumors, where the outcome is generally good, the TMEM count was low.

Tumor Microenvironment of Metastasis density was related positively to development of distant-organ metastasis, independent of lymph node status and tumor grade.

Traditional Diagnosis

“Traditionally, the likelihood of breast cancer metastasis is estimated based on tumor size, tumor differentiation – how similar or dissimilar the tumor is compared to normal breast tissue – and whether it has spread to the lymph nodes. While these are useful measures, TMEM density directly reflects the blood-borne mechanism of metastasis, and therefore may prove to be more specific and directly relevant,” says Dr. Jones.

The next step will be to validate the findings in a larger sample group, researchers say. Also in store is the establishment of a threshold TMEM density for metastasis risk.

Besides non-melanoma skin cancers, breast cancer is the most common malignant disease of women in the developed world. Approximately one in eight women in the United States will be diagnosed with breast cancer at some time in their lives.

Although an estimated 10 percent to 15 percent of patients have an aggressive form of the disease that metastasizes within three years after initial diagnosis, metastasis can take 10 years or longer to occur.

To lessen the risk for the appearance of metastatic tumors, approximately 80 percent of breast cancer patients are treated with adjuvant chemotherapy. The clinical benefit is a 3 percent to 10 percent increase in 15-year survival, depending upon the age of the patient at diagnosis.

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