A team of scientists from University of California San Francisco, University of Texas at Houston, and University of Toronto have a promising lead on distinguishing between the two subtypes of luminal breast cancers, which make up approximately 60% of breast cancers. Luminal A breast cancer accounts for 40% of cases and generally leads to better treatment outcomes than luminal B, where women usually have recurrence and are less likely to respond to hormone therapies such as tamoxifen. Poor distinction between the two has led to overtreatment of many women with luminal A breast cancers, according to Valerie Weaver, PhD, from the Center for Bioengineering and Tissue Regeneration at UCSF.
Motivation for the scientists’ recent study published in Nature Medicine came from previous associations between tumors and altered tissue-level cell mechanics. Using a mouse model of breast cancer, Weaver and Janna Mouw, PhD, found that the extracellular matrix in tumors became stiffer. Cells were able to sense the stiffness of their environment using integrin receptors, and outside-in signaling mechanisms led to the production of miR-18a, which is known to be tumor-promoting. The specific function of miR-18a is to affect the production of the tumor-suppressor protein PTEN, which is often disabled in cancerous cells. Weaver commented on the results: “This discovery of the molecular chain of events between tissue stiffening and spreading cancer may lead to new and more effective treatment strategies that target structural changes in breast cancers and other tumors.”
This is not the first time Weaver’s laboratory has made impactful discoveries. She was the first to recognize that extracellular matrix structural elements become cross-linked prior to cancer progression. Implications of her current findings may reduce the time and cost commitment of distinguishing breast cancer subtypes luminal A and luminal B. “The work provides early evidence that miR-18a is a strong predictor of metastasis and poor survival in women with luminal breast tumors, and that it may be used to distinguish luminal A breast tumors from luminal B breast tumors,” said Laura Van’t Veer, head of the breast oncology program at UCSF. What’s more, the authors of the paper wrote that their findings may explain frequent miRNA alterations across multiple cancer types, giving their work implications beyond breast cancer.