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Breast Cancer Metastases Supported by Bone Microenvironment

The bones are the most common place where metastatic breast cancer cells tend to go. Common treatments for metastatic breast cancer in any location including the bone are chemotherapy, hormonal therapy, targeted therapies, and bone-strengthening medication. Often, bone metastases can be stabilized and managed for long periods of time. However, some breast cancers return after therapy. Now two studies led by Baylor College of Medicine (BCM) may explain why estrogen receptor-positive (ER+) breast cancer sometimes returns in the bone and spreads to other tissues despite effective endocrine therapies directed at ER.

Using animal models that include patient tumor samples, the researchers discovered that the bone microenvironment surrounding ER+ breast cancer cells reduced ER expression in these cells, leading to resistance to endocrine therapy. Their findings were published in the journal Developmental Cell in a paper titled, “The bone microenvironment increases phenotypic plasticity of ER+ breast cancer cells.” In a second study, researchers reported how the bone microenvironment promotes reprogramming of the cancer cells that support their ability to metastasize in the paper titled, “The bone microenvironment invigorates metastatic seeds for further dissemination,” published in the journal Cell.

“Metastasis to other organs is the major cause of cancer-related deaths, and my lab has been interested in this phenomenon for many years,” explained corresponding author Xiang H.-F. Zhang, PhD, the William T. Butler, MD, endowed chair for distinguished faculty and professor of molecular and cellular biology at BCM. “Breast cancer mostly metastasizes to the bone; however, it has remained a mystery why, in more than two-thirds of cases, metastases will not be limited to the bone, but rather subsequently occur in other organs and eventually cause death.”

In the two studies, the researchers applied a series of models and techniques they had previously developed to determine cancer-bone interactions at a single-cell resolution to observe what happens to ER+ breast cancer cells when they metastasize to the bone. They wanted to find out what might contribute to their resistance to endocrine treatment and enhance metastasis to other organs.

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