Antifibrotic drug shows promising effect on breast cancer

The most common breast cancer is HER2-negative. It is so called because it contains small amounts of HER2, one of the proteins that contribute to tumor cell growth. Despite this commonality, HER2-negative cancers develop differently in patients. One goal is therefore to be able to classify tumors more precisely and thus determine the best treatment for each case.

The Clinical Research Unit for Breast Cancer at the Spanish National Cancer Research Center (CNIO) confirms that one feature that helps predict the development of the disease is the rigidity of the substances that provide structure and support to tumor cells – the so-called extracellular matrix. This leads to hardening or fibrosis of the tumor tissue, which in turn affects the way the cells spread.

The CNIO team led by Miguel Ángel Quintela states in a new study published in Clinical cancer research that the prognosis is worse if fibrosis is present.

The connection between fibrosis of the extracellular matrix and tumors, as well as the tendency to metastasize in breast cancer, had already been observed before. But now, “for the first time in a clinical study, the role of fibrosis as a very unfavorable negative prognostic factor has been confirmed,” says Quintela.

An antifibrotic drug for cancer treatment

The study evaluates a new test called MeCo Score®, which analyzes the activity of approximately 1,000 genes in early-stage HER2-negative breast tumor tissue, focusing specifically on genes whose expression is associated with fibrosis.

The test – developed by MeCo Diagnostics, a spin-off of the University of Arizona, based on the work of the study's lead author, Gus Mouneimne – creates a scale for the results. The study confirmed that the higher the score, the more severe the fibrosis and the greater the likelihood of relapse and/or metastasis.

The MeCo Score® also represents an innovative treatment option. Its results show how effective supplementing conventional chemotherapy with the drug nintedanib, which is currently used to treat idiopathic pulmonary fibrosis, can be in these tumors.

This is the first time that a drug with antifibrotic activity has shown efficacy, and very strong efficacy, in cancer.”

Miguel Ángel Quintela, Centro Nacional de Investigaciones Oncológicas

A study with new value

The CNIO's collaboration on this work began because Quintela's group had conducted a study in 2014 in which nintedanib was used in about 130 breast cancer patients. They then investigated whether the drug, when added to chemotherapy, prevented or reduced the formation of new blood vessels in the tumor.

When the group led by Mouneimne at the University of Arizona Cancer Center (Tucson, USA) studied the ability of nintedanib to reduce fibrosis in breast tumors, they found that Quintela's study was the only one in the world that had been conducted on patients. At the request of his American colleagues, the CNIO again requested and received biopsy samples from 73 cases, both before and after experimental treatment with nintedanib combined with chemotherapy. After analysis with MeCo Score®, they found that the cases with a higher fibrosis index had better results in terms of the benefit they were able to obtain from nintedanib.

According to the authors, “this strategy defines a path toward more personalized and cost-effective treatment paradigms for breast cancer and represents the first successful clinical application focusing on tumor fibrosis in oncology.”

Miguel A. Quintela states that this study “could be a first step towards an FDA approval application for the MeCo Score®, although this would require information from many more clinical cases.”