Trial Information

A Phase II Study of the Beta-blocker Propranolol Alone and With Chemotherapy in Patients Receiving Neoadjuvant Treatment for Newly Diagnosed Breast Cancer

While a number of therapeutic options exist for patients with breast cancer (BC), breast
tumor biology is differs across tumors and not all BCs respond to treatment. Identifying a
marker predicting response could spare non-responders unnecessary side effects, cost, and
time. A recent example in BC is bevacizumab, an expensive anti-angiogenic monoclonal
antibody, for which the FDA revoked approval for patients with metastatic BC. While this
targeted therapy may benefit some patients, no appropriate predictive marker has been
identified in the drug development process. An ideal biologic marker would be easy to
perform, reliable, low-cost and non-invasive. A limitation of assessing tumor-based markers
in metastatic BC is the inability to procure tumor tissue at different treatment times. To
circumvent this issue, anti-cancer agents can be assessed pre-operatively, where women with
newly diagnosed BC receive a study drug, alone or with chemotherapy, between diagnostic
breast biopsy and surgical resection. In addition, tumor changes can be directly compared to
modulation of non-invasive markers, such as functional radiographs or blood, to identify a
non-invasive marker predicting tumor response.

The investigators are conducting a neoadjuvant single-institution trial with the
non-selective, inexpensive β -blocker propranolol alone and with chemotherapy in locally
advanced BC. β-blockade regulates angiogenesis in primary breast tumors. In these trials,
the investigators plan to evaluate treatment-related microvascular response via changes in
breast Diffuse Optical Tomography (DOT), a non-invasive, fast, safe, and inexpensive breast
imaging tool. As the optical property contrast from endogenous chromophores (oxyhemoglobin,
deoxyhemoglobin, water, and lipid) provides information on tissue vascularity, it can
monitor response to anti-angiogenic agents. DOT changes occur as early as 1 week after
starting pre-operative therapy. The dynamic DOT system incorporated in these trials is
unique to Columbia University Medical Center (CUMC), as it has been designed by Columbia
biomedical engineers. CUMC's laboratory collaborators have measured this DOT system with
anti-angiogenesis agents in animal models, demonstrating the translational nature of this
project. While non-dynamic DOT has been assessed in other neoadjuvant trials with small
cohorts receiving heterogeneous chemotherapy agents, none have evaluated DOT response to
anti-angiogenic agents.