Chemotherapy Observed to Increase Metastasis Risk in Breast Cancer

Treatment with chemotherapy was observed to increase the risk of metastasis in mouse models of breast cancer, according to a new study published by Science Translational Medicine.

The authors also found that the cellular changes caused by chemotherapy increased the risk of metastasis among human patients with breast cancer.

In the study, the authors used a novel test that predicts whether breast cancer tumors will metastasize.

They discovered that breast cancer metastasizes when 3 types of cells are in direct contact: an endothelial cell, a Tie2-Hi perivascular macrophage (an immune cell involved with blood vessel growth), and a tumor cell that produces high levels of Mena, which is a protein that increases cancer’s ability to invade blood vessels, according to the study.

These types of cells come in contact at the tumor microenvironment of metastasis (TMEM), which is where tumor cells can enter blood vessels, according to the study. The authors reported that tumors with many TMEM sites are more likely to metastasize compared with tumors with few sites.

The investigators conducted TMEM testing on the breast tissue of 3 mouse models that had been previously treated with paclitaxel. For these mice, the investigators found high TMEM activity.

Notably, mice who had received prior chemotherapy had TMEM scores that were 2- to 3-fold higher compared with the scores of mice who did not receive the treatment, according to the study.

Even when treated with doxorubicin plus cyclophosphamide, the authors found similar results.

In TMEM testing on biopsied tissue from 20 patients with breast cancer who were previously treated with paclitaxel followed by doxorubicin plus cyclophosphamide, the authors found that a majority of patients had an increase in TMEM scores after chemotherapy, according to the study.

The investigators observed that 5 patients had a more than a 5-fold increase in TMEM score compared with scores prior to chemotherapy. This may suggest that chemotherapy can lead to increased risk of metastasis.

Additionally, the investigators found that when mouse models of breast cancer were treated with rebastinib—a Tie2 inhibitor that blocks TMEM function—the drug prevented blood vessel permeability and cancer spread linked to TMEM, according to the study.

The new findings provide greater understanding of the mechanisms of chemotherapy-related cancer cell dissemination, potential therapies to block the occurrence, and potential predictive markers to determine which patients should receive pre-operative chemotherapy, according to the study.

Additional studies are needed to further explore the effects of chemotherapy on a larger breast cancer patient population.