Rena Feinman, PhD

Identifying innovative approaches to improve response to therapies for triple-negative breast cancer.

Impact

Triple-negative breast cancer (TNBC) is an extremely aggressive and heterogeneous disease. It accounts for 15-20 percent of all diagnosed breast cancers, and affects young women, particularly African Americans and women with germline BRCA mutations. Although chemotherapy is an effective therapy against TNBC, only 35-40 percent of patients respond to chemotherapy and the majority progress to metastatic disease within three years after diagnosis. There are few targeted therapies for TNBC, making the development of novel and personalized therapies an urgent need. The discovery that the composition of the gut and tumor microbiome, which consist of tens of trillions of bacteria, can influence response to chemotherapy prompted Dr. Feinman and her colleagues to ask if certain types of gut and tumor bacteria increase the efficacy of neoadjuvant chemotherapy by re-activating the patient’s immune system. They aim to identify novel microbiota-associated biomarkers that predict poor outcome—this could lead to the development of personalized microbial-based therapies that harness the immune system of TNBC patients to effectively defeat this disease.

Progress Thus Far

Dr. Feinman and her team are conducting a multi-site prospective observational study in patients newly diagnosed with TNBC and undergoing treatment with standard-of-care neoadjuvant chemotherapy. They have assessed baseline compositions of the gut microbiome in tumor biopsies from 42 participants prior to and after treatment with standard of care neoadjuvant (presurgical) chemotherapy (NAC). Analysis reveals that the composition of the microbiome is predictive of NAC outcome in these patients. Preliminary results showed that the pre-existing composition of immune cells in the tumor microenvironment also influences patient response to NAC. Dr. Feinman and her team are also characterizing the density and spatial relationship between TNBC tumor cells and the specific immune cells that surround them. Initial findings suggest differences in the abundance and localization of tumor infiltrating T cells, macrophages, and bacteria in the tumor microenvironment of successful NAC versus unsuccessful NAC. As a secondary focus, the team also looked at whether the imbalance of beneficial and harmful gut bacterial communities play a causative role in TNBC progression and resistance to therapy. Studies are underway.

What’s next

Dr. Feinman and her colleagues will continue to enroll patients at multiple participating clinical sites and meet their accrual goal of 49 patients. In the coming year, they will complete the sequencing of the gut and tumor microbiome and correlate microbiota profiles with response to NAC in the context of several clinical variables including tumor stage, residual cancer burden, antibiotic use, body mass index, age, and race/ethnicity. Other studies will continue to investigate how imbalances in the gut microbiome affect the biology of TNBC.