Anti-fibrotic Drug Shows Promise in Breast Cancer Treatment

The most prevalent type of breast cancer is known as HER2-negative breast cancer, so named because it has low levels of HER2, a protein that aids in the proliferation of tumor cells. Even with this shared characteristic, HER2-negative malignancies develop differently in each patient, therefore one objective is to be able to more precisely classify tumors in order to establish the optimal course of treatment for each individual case.

The Spanish National Cancer Research Center’s (CNIO) Breast Cancer Clinical Research Unit affirms that the extracellular matrix, or the stiffness of the materials that support and structure tumor cells, is one characteristic that contributes to the prediction of the disease’s course. This results in fibrosis, or the hardening of the tumor tissue, which modifies the cells’ ability to propagate.

In a recent study published in Clinical Cancer Research, the CNIO team, headed by Miguel Ángel Quintela, reveals that the prognosis deteriorates with the presence of fibrosis.

It was previously known that tumors and the likelihood of metastasis in breast cancer were related to extracellular matrix fibrosis. However, “for the first time in a clinical study, the role of fibrosis as a very adverse negative prognostic factor has been confirmed,” according to Quintela.

An antifibrotic medication used to treat cancer
The study assesses a novel test known as MeCo Score®, which examines the activity of roughly one thousand genes in tissues from early-stage HER2-negative breast tumors, with a particular emphasis on genes whose expression is linked to fibrosis.

The test creates a scale for the outcomes and was created by MeCo Diagnostics, a University of Arizona spin-off, based on the research of Gus Mouneimne, the study’s primary author. The results of the study have confirmed that a higher score indicates more fibrosis and increases the risk of metastasis and/or recurrence.

MeCo Score® also considers a novel course of treatment. Its findings show how well nintedanib, a medication now used to treat idiopathic pulmonary fibrosis, can work in addition to standard chemotherapy to treat these tumors.

“This is the first time that a drug with antifibrotic activity has demonstrated activity, but also very potent one, in cancer.”- Miguel Ángel Quintela, Centro Nacional de Investigaciones Oncológicas

A study that has fresh significance
The CNIO’s involvement in this effort began when Quintela’s group administered nintedanib to roughly 130 patients with breast cancer in a 2014 research. They then looked at whether the medication prevented or decreased the growth of new blood vessels in the tumor when added to chemotherapy.

The University of Arizona Cancer Center (Tucson, USA) team led by Mouneimne discovered that Quintela’s study was the only one in the world that involved patient participation when examining nintedanib’s capacity to lessen fibrosis in breast tumors. In response to the pleas of his colleagues in America, the CNIO once more gathered biopsy samples, this time from 73 cases, pre- and post-experimental treatment with nintedanib with chemotherapy. Upon utilizing MeCo Score® for analysis, it was discovered that patients with a greater fibrosis index demonstrated superior outcomes with regard to the potential benefits of nintedanib.

According to the researchers, “this strategy defines a pathway toward more personalized and lower-cost treatment paradigms for breast cancer and represents the first successful clinical application targeting tumor fibrosis in oncology” .

“A first step towards the application for approval of the MeCo Score® by the US Food and Drug Administration (FDA), although this would require information from many more clinical cases,” according to Miguel A. Quintela, describes this study.

For more information: High mechanical conditioning by tumor extracellular matrix stiffness is a predictive biomarker for anti-fibrotic therapy in HER2-negative breast cancer, Clinical Cancer Research, https://doi.org/10.1158/1078-0432.CCR-24-1518