Breast Cancer Metastasis Could be Predicted

In the US alone, 12,5% of women are diagnosed with breast cancer at some time in their life and this is the most common malignant disease of women living in the developed world, 10 to 15 percent of them having an aggressive form which metastasizes within three years after initial diagnosis, normally metastasis taking 10 or more years to occur. While adjuvant chemotherapy decreases the risk of developing metastatic tumors for about 80 percent of patients (with a 3 to 10 percent increase in 15-year survival, depending on their age at diagnosis), an approximate of 40 percent of the patients relapse and develop metastatic disease.

About 40,000 women die of metastatic breast cancer every year, distant organ metastasis via the bloodstream being the most common cause of death. A recent study which could lead to a test to predict the likelihood of this type of metastasis could change the way breast cancer is treated.

The study was carried on by researchers at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and identified a new marker for cancer metastasis, called TMEM (Tumor Microenvironment of Metastasis). Senior author Dr. Joan G. Jones, professor of clinical pathology and laboratory medicine at Weill Cornell Medical College and director of Anatomic Pathology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and first author Dr. Brian D. Robinson, resident in Anatomic Pathology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center state that a tissue test for metastatic risk could alleviate worries of metastatic cancer and prevent toxic and costly measures like radiation and chemotherapy and could also offer a better way to classify patients as either low risk of high risk, preventing over-treatment or under-treatment of the disease.

The study was based on the previous findings of co-author Dr. John S. Condeelis of the Albert Einstein College of Medicine who had previously identified a link between blood-borne or systemic metastasis and a three-part association between invasive carcinoma cells, perivascular white blood cells (macrophages) and the endothelial cells that line vessel walls in animals. Jones and Robinson worked on confirming these findings in humans, developing a triple immunostain for human breast cancer samples that simultaneously labels the three cell types which they called TMEM. In the case study that followed, they proved that TMEM density was associated with the development of distant-organ metastasis, independent of lymph node status and tumor grade, being more than double in the group of patients who developed systemic metastases compared with the patients with only localized breast cancer.

“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 team is currently working on a way of measuring TMEM with more accuracy and working on a way to identify a threshold of TMEM density for metastasis risk after validating their findings on a larger sample group (the current experiment was carried on tissue samples from 30 patients with invasive ductal carcinoma of the breast who developed systemic, distant-organ metastases and compared to matched controls that had only localized disease (i.e., invasive ductal carcinoma limited to the breast or with regional lymph node metastasis only).