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Chemotherapy opens a molecular door for metastasis, and the aggressive spread of breast cancer, according to a new study that promises to prompt some worries – and further research.

The mouse models and biopsies of breast cancers of 20 women showed that chemo improves metastatic conditions at key tumor locations, according to the study in the journal Science Translational Medicine.

“Our finding that chemotherapy, when given in the setting of clinically active disease, may promote cancer cell dissemination is of major concern,” writes the team, from the Albert Einstein College of Medicine and the Montefiore Medical Center.

A crucial site called the tumor microenvironment of metastasis, TMEM, is the focus of the study. The TMEMs are described by the team as the locus of three kinds of cells that are a waystation for the spread of breast cancer. The three are: an endothelial cell from a blood vessel, a Tie2-Hi perivascular macrophage immune cell linked to vascular growth, and a tumor cell producing high levels of the protein Mena that enhances a tumor’s spread.

Together, the three open a pathway to send even shrinking tumors a kind of lifeboat to other sites throughout the body, they report.

The study looked at three mouse models of breast tumors that had been treated with a chemo drug called paclitaxel. The chemotherapy increased TMEM “scores” by as much as a factor of three over the mice which did not undergo the treatment, they report. Similar increases in the metastatic risk were found with the chemo drugs doxorubicin plus cyclophosphamide, they add.

The TMEM sites were also investigated in biopsies from 20 women who had undergone chemo with the three drugs. The TMEM scores increased – and increased five-fold in five of the patients’ tumors, they write.

They also suggest a possible solution: a drug that inhibits Tie2 and essentially blocks the TMEM site dynamic. The drug is called rebastinib.

The two main Einstein authors of the latest study have a patent application pending that “covers methods of detecting and reducing chemotherapy-induced pro-metastatic changes in breast tumors,” the school said in a statement.

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