Breast cancer research makes possible the development of new therapies for breast cancer. Through clinical trials and work in research labs, including those at Dana-Farber Cancer Institute, treatments and drugs are explored — and if successful, are later able to be offered to patients who need them.
Breast cancer today is seen as not one, but multiple different diseases. Any patient’s cancer is distinct, not only in the molecular makeup of the tumor cells, but also the patient’s response to prior therapy and the state of their immune system. As a result, “the future of breast cancer therapy is tied to the idea of individualizing treatment for each patient, and research being done today is increasingly making that possible,” says Sara Tolaney, MD, MPH, chief of the Breast Oncology Program at the Susan F. Smith Center for Women’s Cancers at Dana-Farber Brigham Cancer Center.
Hot areas of breast cancer research
Some of the hot areas of research in breast cancer include:
New anti-cancer weapons such as drugs that use antibodies to target cancer cells
Dana-Farber researchers have been involved in the development of drugs made up of an antibody linked to a chemotherapy drug. These so-called antibody-drug conjugates, or “smart bombs,” use the antibody to home in on receptors on the surface of cancer cells and deliver the chemotherapy drug to the tumor, bypassing normal cells.
One such drug is T-DM1 (Kadcyla), a combination of the drug Herceptin and a chemotherapy compound, emtansine. It is approved to treat HER2-positive metastatic breast cancer in patients previously treated with Herceptin (trastuzumab) and taxane chemotherapy, and to treat patients with early stage HER2-positive breast cancer who have residual disease after preoperative HER2-directed therapy.
Another recently approved drug of this type is sacituzumab govitecan (Trodelvy) for some patients with triple-negative breast cancer. This compound is an antibody-drug conjugate containing a monoclonal antibody linked to a metabolite of the chemotherapy drug irinotecan. The antibody selectively binds to a tumor-associated protein, TROP2. Dana-Farber investigators are now studying its safety and effectiveness in combination with other therapies, including immunotherapy agents.
Other antibody drugs are recently approved or in development, “and a lot of these agents look exciting,” says Tolaney.
The HER2-directed agent trastuzumab deruxtecan is a novel antibody drug conjugate that has been approved for patients with pretreated metastatic HER2-positive breast cancer and has demonstrated unprecedented activity in this space. Work is now ongoing to see if it can be used as a first line treatment for metastatic HER2-positive disease, and to see if it could be used after surgery in patients with early stage HER2-positive breast cancer.
Immunotherapy, which harnesses the patient’s immune system to attack the cancer
Enormous amounts of research are going into immunotherapy, which has become a pillar of treatment for several types of cancer, including melanoma, lung, kidney, head and neck, liver cancer, and leukemia. Efforts to harness the patient’s immune system to treat breast cancer have lagged because in general, breast tumors have fewer cancer-associated mutations that distinguish the cancer cells from normal cells.
“In breast cancer, there are not a lot of immune cells in the tumor itself, and the tumor mutational burden is lower, which makes it more difficult” for the immune system to recognize and attack the cancer cells, explains Tolaney.
However, one immunotherapy drug has been approved to treat triple-negative breast cancer, and Dana-Farber researchers are investigating the use of immunotherapy combinations to prod the immune system into action against breast cancer.
Identification of patients who may be able to receive less treatment and still have excellent outcomes
An important part of individualizing breast cancer care is to take advantage of better therapies that are now available, some of them with fewer side effects than traditional treatments.
“We are now starting to understand which biomarkers allow us to ‘right-size’ therapy, matching the treatment to the patient and decreasing side effects,” explains Tolaney. “We have several studies that are aiming to use treatments such as antibody-drug conjugates” which may enable some patients to be spared more-toxic side effects.
Studying mechanisms that cause breast cancers to become resistant to drugs, so that future therapies can be designed to overcome resistance
Breast cancers can become resistant to chemotherapy and other treatments, and this is the reason for disease progression among patients with metastatic breast cancer. The study of resistance and ways to prevent it is a major focus of breast cancer researchers everywhere.
“One thing our group is trying to do is to get tumor biopsies at the time the cancer progresses and study these samples to understand what the mechanism of resistance is,” says Tolaney. “This will help us figure out future therapies.”
About the Medical Reviewer
Dr. Tolaney received her undergraduate degree from Princeton University in 1998 and her medical degree from UC San Francisco in 2002. She subsequently completed her residency in Internal Medicine at Johns Hopkins University, and fellowships in hematology and medical oncology at Dana-Farber Cancer Institute. She obtained a Masters in Public Health from the Harvard School of Public Health in 2007. In 2008, she joined the staff of Dana-Farber Cancer Institute and Brigham and Women's Hospital, where she serves as Chief of the Division of Breast Oncology. She is a breast medical oncologist whose research focuses on the development of novel therapies in the treatment of breast cancer. She has been instrumental in developing several treatment approaches for breast cancer, including approaches focused on tailoring therapy for early stage HER2+ disease, use of cdk 4/6 inhibitors, antibody drug conjugates, and immunotherapy.
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