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Study demonstrates paclitaxel treatment promotes breast cancer dissemination and metastasis

Results from a study published in Science Translational Medicine demonstrates certain types of chemotherapy promote breast cancer tumour cell dissemination and metastasis, including increased circulating tumour cells (CTCs) and TMEM / MetaSite scores (MS), in addition to enhanced expression of pro-metastatic Mena protein isoforms.

Consistent with the known requirements for Mena in breast cancer metastasis, paclitaxel-induced dissemination was found to be dependent on Mena protein expression.

Previous studies had demonstrated that animals grafted with MMTV-PyMT Mena-null breast cancer tumours fail to develop CTCs or lung metastasis, and paclitaxel-treatment did not promote metastasis of Mena-deficient tumours in the current study.

The investigators used the research version of MetaStat’s clinically validated and CLIA-approved MetaSite Breast test to quantify changes in the number of MetaSites before and after chemotherapy treatment.

In tumour samples from breast cancer patients, neoadjuvant chemotherapy (NEC) consisting of paclitaxel after doxorubicin plus cyclophosphamide increased MetaSite scores (MS) and expression of the pro-metastatic MenaINV isoform.

Preclinical studies of patient-derived xenograft and PyMT murine models also demonstrated that chemotherapy increased the density of MetaSites and levels of the MenaINV isoform.

“The ability to accurately define a pro-metastatic phenotype has the potential to provide important and useful information towards the effective management of patients newly diagnosed with breast cancer,” stated Michael J. Donovan, MD, PhD, acting Chief Medical Officer of MetaStat who develop the MetaSite test.

“These data provide insight into why some patients with pathologic complete responses (pCR) following chemotherapy do not derive long-term benefit,” stated Douglas A. Hamilton, MetaStat President and CEO. “As we accelerate our therapeutic program aimed at preventing aggressive cancer from spreading, we are further encouraged by the potential added benefit to patients of combination therapy with taxanes and Mena-targeted drugs to block chemotherapy-induced cancer cell dissemination and metastasis.”

Source: BusinessWire



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