Neoadjuvant Chemotherapy May Induce Breast Cancer Metastasis

A neoadjuvant chemotherapy combination used to treat breast cancer increases the risk of disease metastasis, according to recent research published in Science Translational Medicine (published online July 5, 2017; doi:10.1126/scitranslmed.aan0026).


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Metastasis significantly increases the risk of death in patients with breast cancer. Breast cancer cells disseminate through cancer cell intravasation sites – termed tumor microenvironment of metastasis (TNEM). These sites are regarded as prognostic markers for breast cancer metastasis.

George Karagiannis, PhD, department of anatomy and structural biology, Albert Einstein College of Medicine (Bronx, NY), and colleagues conducted a study to examine the effects of a neoadjuvant chemotherapy regimen (paclitaxel with doxorubicin plus cyclophosphamide) in breast cancer tissues. Researchers found that while the combination regimen significantly decreased the size of tumors, there were some unintended and adverse effects as well.

Results of the analysis showed that the chemotherapy regimen increased the density and activity of TNEM sites and MENAINV expression, as well as promoted distant metastasis. Additionally, researchers noted that TNEM score and MENAINV expression pattern were both increased in the residual breast cancer treated with the chemotherapy regimen. This finding, authors of the study assert, suggests that chemotherapy increases the risk of metastatic dissemination, despite deceasing tumor size.

Researchers note that there are ways of minimizing risk of metastasis – including administering the TIE2 inhibitor rebastinib or targeting the MENA gene.

“One approach would be to obtain a small amount of tumor tissue after a few doses of preoperative chemotherapy,” Dr Karagiannis said in an interview (July 7, 2017). “If we observe that the markers scores are increased we would recommend discontinuing chemo and having surgery first, followed by post-operative chemo.”

More extensive trials are in the works to validate this recommendation. Nonetheless, authors of the study concluded that “TMEM score increases and MENA isoform expression pattern changes with chemotherapy and can be used in predicting prometastatic changes in response to chemotherapy.”—Zachary Bessette