Potential Treatment for Aggressive Triple-Negative Breast Cancer

Identified cancer driver may be key to increasing survival in metaplastic breast cancer patients.

A gene that drives the development of metaplastic breast cancer was identified in a new study published in the Journal of the National Cancer Institute.

Metaplastic breast cancer is a rare and aggressive subtype of triple-negative breast cancer that accounts for less than 1% of all breast cancers, according to the Susan G. Komen Foundation. Unfortunately, due to its aggressive nature and its unresponsiveness to chemotherapy, the 3-year survival rate is only 40%.

In the study, investigators identified the same genetic mutation in 39 of 40 tumor samples obtained from metaplastic breast cancer patients. The mutation in the gene RPL39 is considered an oncogene, because it is overexpressed in 1 of 5 breast cancers, according to the study.

RPL39 regulates the expression of the enzyme inducible nitric oxide synthase (iNOS), and the results of the study showed that patients with a high expression of RPL30 and iNOS had lower overall survival.

The investigators then examined the effects of an iNOS inhibitor on the treatment of metaplastic breast cancer. The results showed that the compound L-NMMA was able to shrink the tumors in mice models with metaplastic breast tumors.

“The results showed elimination of the cancer in nearly all of the mice when combined with standard chemotherapy,” said lead investigator Jenny C. Chang, MD. “Our goal is to turn metaplastic breast cancer from a debilitating disease into a chronic illness.

“We not only uncovered the biological pathway stimulating cancer growth, but we found a compound that blocked it, increasing the survival of mice carrying human metaplastic breast tumors.”

Currently, Houston Methodist hospital is enrolling patients diagnosed with metaplastic breast cancer into a phase 1 clinical trial for L-NMMA, according to the authors.