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New potential treatment for triple-negative breast cancer identified

New potential treatment for triple-negative breast cancer identified

The drug called 5-aza-2′-deoxycytidine (decitabine) which is approved by the U.S. Food and Drug Administration (FDA) for the treatment of myelodysplastic syndrome may be beneficial for the treatment of triple-negative breast cancer (TNBC), according to a study published in the  Journal of Clinical Investigation.

The study was conducted by Liewei Wang, a researcher at Mayo Clinic and counterparts to identify the relevance of decitabine for treatment of TNBC.

Triple-negative breast cancer (TNBC) is a heterogeneous disease with poor prognosis that lacks targeted therapies, especially in patients with the chemotherapy-resistant disease. It is one of the most aggressive and lethal types of breast cancer.  Testing negative for estrogen receptors (ER-), progesterone receptors (PR-), and HER2 implies the presence of TNBC. These negative results mean that the growth of the cancer is not supported by the hormones estrogen and progesterone, nor by the presence of too many HER2 receptors. Therefore, triple-negative breast cancer does not respond to hormonal therapy or therapies that target HER2 receptors.

Silencing of tumor suppressors induced by DNA methylation is common in cancer. Decitabine is a DNA methyltransferase (DNMT) inhibitor that can cause the reversal of promoter DNA hypermethylation. The drug has proven effective in treating hematological neoplasms. However, its antitumor effect varies in solid tumors, stressing the importance of identifying biomarkers predictive of therapeutic response.

This study was part of the ongoing work from the Breast Cancer Genome-Guided Therapy (BEAUTY) study, co-led by Matthew Goetz, M.D., a Mayo medical oncologist and Judy Boughey, M.D., a Mayo breast surgeon. The BEAUTY study generated patient-derived xenografts (immortalizing breast tumor cells) from patients with breast cancer treated with chemotherapy.

“There is a great need to identify additional treatment options for triple-negative breast cancer, which is one of the most difficult to treat subtypes of breast cancer,” says Mayo researcher Wang, “The study is a demonstration that we can take advantage of many existing FDA approved drugs to expand their usage by better understanding the mechanisms of how they work and applying them to other cancers.”

“Patients whose tumor does not respond well to chemotherapy are known to be at significantly increased risk of recurrent breast cancer and death,” says Dr. Boughey. “Therefore our focus is to identify new treatment options for these patients.”

Key findings:

  • The drug 5-aza-2′-deoxycytidine (decitabine)  could significantly inhibit the growth of triple-negative breast cancers, and importantly this effect was also seen in tumors resistant to chemotherapy.
  • The drug response was dependent on the presence of certain critical proteins called DNA methyltransferase proteins that are present in only a subset of triple negative breast cancers.
  • DNA methyltransferase proteins were present, decitabine showed an effect in triple-negative breast cancer at a low therapeutic dose.
  • The low doses would result in less toxicity and might allow the drug to be used for a longer time, all of which might help to achieve greater therapeutic efficacy.

Dr. Goetz, plans are underway to prospectively study the impact of decitabine in a prospective clinical trial, called BEAUTY2, which is focused on women with triple negative breast cancer that is resistant to chemotherapy.

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Source: With inputs from JCI

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