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Weill Cornell Medicine has been awarded a nearly $6.5 million, four-year grant from the Department of Defense as part of a multi-institutional Transformative Breast Cancer Consortium. The award will fund research on the mechanisms underlying triple negative breast cancer (TNBC), with the hope of one day developing therapeutics for this aggressive and difficult to treat form of breast cancer.

The research initiative, titled "Therapeutic Targeting of Breast Cancer and Host Immune Responses at Inflection Points in the Disease Trajectory," establishes a consortium of researchers who build on one another's strengths to accelerate scientific discoveries in breast cancer and to translate them to breast cancer care, said principal investigator Dr. Silvia C. Formenti, chair of the Department of Radiation Oncology and the Sandra and Edward Meyer Professor of Cancer Research at Weill Cornell Medicine and radiation oncologist-in-chief at NewYork-Presbyterian/Weill Cornell Medical Center.

In addition to Dr. Formenti, consortium members from Weill Cornell Medicine include Dr. Sandra Demaria, professor of radiation oncology and of pathology and laboratory medicine, Dr. Lisa Newman, chief of the Section of Breast Surgery at NewYork-Presbyterian/Weill Cornell Medical Center and Weill Cornell Medicine, Dr. Melissa Davis, associate professor of cell and developmental biology research in surgery, Dr. Eleni Andreopolou, associate professor of clinical medicine at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center, and Helen Schiff, patient advocate.

Dr. Formenti and her team are studying breast cancer as a series of inflection points—events such as diagnosis, the detection of tumor spread, and the response of tumors to treatments—as identified by patient advocates. The research team is then determining where scientists can intervene to improve outcomes.

One such inflection point is the response of the tumor to chemotherapy followed by surgery in women with TNBC. Women with TNBC who have residual disease, meaning cancer cells that are still present in surgically removed breast tissue and lymph nodes upon examination by a pathologist, have poorer survival rates than women whose disease has completely responded to treatment.

“These women do not have a lot of treatment options,” said Dr. Formenti. “No clinical trials have really changed the outcome of patients who have residual disease.”

To better understand how to advance treatment in women with TNBC, Dr. Formenti and her research team are in the process of creating organoids, which are three-dimensional structures grown in the laboratory to model disease processes.

Some of the organoids will be grown from residual disease cells collected from patients. “You can treat these organoids like a little preclinical experiment,” she said.  For example, scientists can study how immune cells from the blood interact with the organoid, which is currently not possible with other cell culture models. “Maybe immune cells engage with tumor cells but aren’t capable of killing them,” she said.

Growing organoids from tissue samples from women who do not have residual disease is also possible. “You can then ask a lot of questions about what went right and wrong in the disease process and with treatment,” Dr. Formenti said.

The goal is to have a large repository of tissues from which to build a variety of organoids, Dr. Formenti said. Researchers will then be able to study these tissues to answer questions about gene expression, epigenetic changes—or how environmental factors and behaviors alter how genes signal and affect the immune response, and the process of metastasis.

Members of the Transformative Breast Cancer Consortium include researchers in molecular biology, cancer genetics, cancer epigenetics and signaling, and immunotherapy, and patient advocates from Harvard Medical School and Brigham & Women’s Hospital, Cedars-Sinai, Los Angeles and Duke University School of Medicine. 

In addition to two other large Department of Defense grants received since she joined Weill Cornell Medicine, “this Department of Defense award really contributes to the joint effort among departments here, including medical oncology and surgical oncology, to build a center of excellence in breast cancer,” Dr. Formenti said.

This article first appeared on WCM Newsroom.