BEAUTY Combines Sequencing, Avatars

Researchers at the Mayo Clinic Cancer Center in Rochester, MN, have launched a clinical study that pairs whole-genome sequencing with mouse “avatars” in an effort to bring clinical care closer to individualized treatment.

The Breast Cancer Genome Guided Therapy (BEAUTY) study involves 200 women with nonmetastatic breast cancer receiving chemotherapy prior to surgery. Before starting chemotherapy, investigators will sequence both cancerous and healthy cells to identify tumor-specific changes for each patient. For patients with disease that is resistant to standard chemotherapy, tumor cells will also be sequenced to determine which mutations helped them survive.

Study co-leaders, Judy Boughey, MD, a breast surgeon, and Matthew Goetz, MD, an oncologist, expect to find known mutations for which drugs already exist as well as targets for new drugs.

In parallel, the investigators will implant tumor samples taken before and after chemotherapy into 2 immunosuppressed mice, creating individualized mouse avatars, or stand-ins, that represent each patient. The avatars immortalize the tumors in live animals to factor in complexities such as the role of the microenvironment in the progression and metastatic potential of a cancer cell.

For a patient with recurring disease, the researchers plan to increase the number of avatars so that they can test multiple drug candidates at once. Further, if a new drug emerges in the future, it can also be tested in that patient's avatars.

“We're not ready yet to introduce tumor genome sequence-based selection of drugs into the neoadjuvant setting, but the avatars give us a way to prospectively study these patients and rationally move towards more individualized therapy,” says Goetz.

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