How Yale is Rewriting the Rules for Breast Cancer Treatment

Breast cancer treatment has come a long way, but for patients with metastatic disease, options remain limited. Now, researchers at Yale Cancer Center and Yale School of Medicine are leading a bold new trial to shift the paradigm. The study, called EVOLVE, will track how tumors mutate and respond to therapy in near real time, allowing doctors to adapt treatments based on how the cancer is changing—not just how it started.

Backed by up to $28 million in funding from the Advanced Research Projects Agency for Health, or ARPA-H, the study will enroll up to 700 patients with metastatic breast cancer. The goal is to make care more precise and more personal by using tumor biopsies, imaging, blood samples, and medical records to monitor cancer progression as it happens.

According to Dr. Eric Winer, director of Yale Cancer Center and physician-in-chief of Smilow Cancer Hospital, this trial will take advantage of a highly collaborative national network. “The TBCRC is uniquely positioned to enroll a diverse patient population and collect biospecimens that will help us develop and refine treatment,” he said.

Winer is one of six principal investigators leading the effort, along with Yale’s Dr. Ian Krop, chief clinical research officer at YCC. The project also involves researchers from the University of North Carolina Lineberger Comprehensive Cancer Center, Johns Hopkins, and other institutions in the Translational Breast Cancer Research Consortium.

What makes EVOLVE different is its design. Most clinical trials test a fixed treatment plan, but this one is structured to shift course. According to Dr. Lisa Carey, the trial’s lead investigator at UNC, the study will “adapt treatment as a tumor changes” using biomarkers, including circulating tumor DNA, to guide decisions.

Nearly 90% of patients with metastatic breast cancer develop resistance to therapy. According to the researchers, this trial will help identify resistance early—before symptoms worsen—and will also work to uncover new biomarkers that can predict whether a treatment will work at all.

“This is about using what we learn in the lab to make better decisions for real people, right now,” said Krop. “When we understand the biology of resistance, we can guide the use of next-generation therapies in smarter ways.”

EVOLVE is one of several projects funded by ARPA-H, a new federal agency created in 2022 to support ambitious, high-impact biomedical research. According to ARPA-H, the broader initiative will also fund the development of new tools, platforms, and models that will support precision oncology across cancer types.

At Yale, other researchers are already contributing to ARPA-H efforts. In 2023, Dr. Richard Edelson helped secure one of the agency’s first grants, focused on using mRNA to direct the immune system to fight cancer, lupus, and other diseases. In 2024, Yale’s Dr. Todd Constable received ARPA-H support to develop an affordable breast MRI alternative designed for use in community clinics.

These investments reflect a growing urgency to close the gap between scientific possibility and clinical reality. According to Winer, “Over 40,000 people in the U.S. die of breast cancer every year. We’ve made real progress, but there’s still a long way to go.”

By combining data, collaboration, and cutting-edge technology, EVOLVE hopes to move breast cancer care into a new era—one where treatment adapts with the disease and where fewer lives are lost waiting for science to catch up.