The Terri Brodeur Breast Cancer Foundation has awarded grants to three scientists working in the field of breast cancer research. Each will receive $100,000 for their two-year fellowship.

One of the recipients works at the Dana-Farber Cancer Institute, one from the Massachusetts General Hospital Cancer Center and one is from the Fred Hutchinson Cancer Research Center. This is the 13th year TBBCF has awarded grants to scientists working toward a cure for breast cancer. Since 2006, TBBCF has awarded 40 breast cancer researchers $4 million in research grants. These awards are intended to support PhD, MD/PhD and MD physician scientists at early stages of their research careers to enable them to develop independent careers in breast cancer research. The Foundation seeks to fund broadly across all relevant disciplines and as such focus areas can include basic, preclinical and clinical research.

This year’s recipients are:

Arko Dasgupta, PhD

Fred Hutchinson Cancer Research Center

Breast cancer is a major killer in the United States and metastases are the primary cause of breast cancer-related deaths. Approximately 30% of breast cancer patients will develop metastases during their lifetime. Few prognostic factors predict metastases as well as the presence of dormant disseminated tumor cells (DTCs) – cells that have escaped from the primary breast tumor early in the disease and exist in a dormant state in distant organs until they develop in some patients as overt metastases. Clinical evidence suggests that eradication of DTCs would prevent metastasis, however, currently no therapies specifically target these metastases-initiating cells. Indeed, DTCs are resistant to chemotherapy and other targeted therapies, and very little is known about what enables DTC survival despite multiple rounds of chemotherapy.

Breast DTCs reside in a perivascular niche (PVN) – areas within a tissue that are occupied by blood vessels – of distant tissues such as lung, bone marrow, brain, liver and lymph node. Importantly, chemotherapy itself has been show to elicit responses that alter the tumor microenvironment that also contribute to chemo-resistance in other cancers such as prostate cancer.

This may be associated with the induction of DNA damage and the consequent change in factors released by blood vessels – a phenomena that remains unexplored in the context of breast DTCs. Preliminary data generated by Dr. Dasgupta suggests that the PVN protect DTCs from chemotherapy. Accordingly, eradicating DTCs for metastasis prevention will require a much deeper understanding the dynamic relationship between DTCs and their microenvironment (PVN).

As a Terri Brodeur Fellow, Dr. Dasgupta will couple novel, biologically relevant, in vivo models with high throughput technologies to discover key targets in the PVN that can be translated into curative therapies in patients. He first aims to describe how the PVN responds to chemotherapy in vivo and identify if targeting factors that change in response to chemotherapy can chemo-sensitize breast DTCs. Additionally, he will identify the signaling that is active in the PVN in a chemotherapy setting; the goal here is to discover signaling pathways that can be muted to prevent chemo-protective responses from the PVN. Lastly, he will perform proof-of-concept studies in pre-clinical mouse models of breast cancer dormancy. His overarching goal is to design better treatment regimens to eradicate chemo-resistant DTCs to prevent metastatic breast cancer-associated mortality.

Dr. Arko Dasgupta earned his Ph.D. in Genetics and Biochemistry at Dartmouth College, under the supervision of Dr. Jay Dunlap and Dr. Jennifer Loros. During his Ph.D., he studied the circadian control of gene expression, as well as photo-biology of light receptors that play a key role in control of circadian rhythms. He discovered that rhythmic, time of day-specific, gene expression is finely tuned to phase-specify metabolic activities in organisms and that post-transcriptional control plays a key role in circadian gene expression. Dr. Dasgupta is currently a post-doctoral fellow at Fred Hutchinson Cancer Research Center in the lab of Dr. Cyrus Ghajar.

Sheng Sun, PhD

Massachusetts General Hospital Cancer Center

The majority of breast cancers express hormone receptors, and therapies that antagonize hormonal signaling via these receptors are the most effective treatments for hormone receptor-positive metastatic breast cancer (HR+ MBC). Unfortunately, for the vast majority of patients with hormonal therapy-refractory MBC, the mechanisms of resistance remain poorly understood. Thus, identifying new mechanisms of hormonal therapy resistance and understanding how to overcome them will have direct and immediate relevance to the therapy of patients with MBC. We have identified novel gene fusions in 14% of patients with HR+ MBC and provided strong evidence that these tumor-specific genetic rearrangements are powerful drivers of treatment resistance and poor outcomes. Successfully tracking and therapeutically targeting these fusions could thus have a major impact on patient outcomes. We hypothesize that patient-derived circulating exosomes (tiny cell-derived vesicles that circulate in the bloodstream) are likely to contain unique nucleic acids and proteins corresponding to the fusions that could potentially serve as novel biomarkers.

We propose to credential these patient-specific rearrangements as blood-based markers of disease burden, clinical response and treatment outcome in MBC. This work will pave the way for effective disease monitoring that will facilitate the clinical development of targeted therapeutics to overcome treatment resistance mediated by these genetic drivers.

Dr. Sheng Sun obtained his Ph.D. in Biomedical Sciences at The University of Texas MD Anderson Cancer Center. During his doctoral studies, Dr. Sun investigated the function and regulation of ESCRTs (Endosomal Sorting Complex Required for Transport), the protein complexes involved in endosomal sorting and exosome biogenesis. Dr. Sun is currently a postdoctoral research fellow at the Massachusetts General Hospital Cancer Center/Harvard Medical School in the laboratory of Dr. Leif W. Ellisen.

Adrienne Gropper Waks, MD

Dana-Farber Cancer Institute

Following many important advances in treating HER2-positive breast cancer over the past two decades, a large majority of patients with non-metastatic HER2-positive tumors are cured with today’s treatments. For this majority of patients who do well in the long-term, we must begin to identify ways to cure HER2-positive breast cancer with less toxic treatments.

Modern treatment regimens for stage II and III non-metastatic HER2-positive breast cancer consist of multiple chemotherapy agents plus HER2-directed therapy with trastuzumab (Herceptin, H) and sometimes pertuzumab (Perjeta, P). Scaling back the number of chemotherapy agents used may allow patients to maintain better quality of life while on treatment, as well as decrease the chance of rare but serious chemotherapy complications.

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As a Terri Brodeur fellow, Dr. Waks plans to conduct a clinical trial investigating a new treatment approach in stage II and III HER2-positive breast cancer, with the goal of allowing select patients to receive less chemotherapy

We know that in patients who receive breast cancer treatment before breast surgery, those who have all cancer eradicated from the breast and lymph nodes at the time of surgery (“pathologic complete response”) have an excellent prognosis. In our clinical trial, patients will be treated before surgery with paclitaxel, trastuzumab, and pertuzumab (“THP”), and those who achieve pathologic complete response at surgery—and have an excellent prognosis on that basis—will go on to receive further HP post-surgery, without any additional chemotherapy. Our primary goal in the trial is to assess the acceptability of this treatment approach to patients and their doctors. We hope that this trial, which is a precursor to a large international trial investigating the same approach, will be a step toward establishing HER2-positive breast cancer treatments that are highly effective for a select patient group, and also maximize patient quality of life.

Dr. Waks conducted her undergraduate studies at Princeton University and then obtained her M.D. degree at Harvard Medical School. She completed residency training in internal medicine at Brigham and Women’s Hospital in Boston, MA, where she was selected to serve for an additional year as a Chief Resident in internal medicine. She is currently a clinical and research fellow in medical oncology at Dana-Farber Cancer Institute, where she will shortly join the staff as an attending physician in breast oncology at the Dana-Farber Susan F. Smith Center for Women’s Cancers, and an instructor at Harvard Medical School.

About TBBCF

In 2005, two friends, Norma Logan (1958-2006) and Sandy Maniscalco started the Terri Brodeur Breast Cancer Foundation (TBBCF). The desire to establish a non-profit organization was from frustration at seeing successful fundraising efforts being diverted from research to cover organizational overhead. Determined to address this issue and ensure money was directed at finding a cure, these women established a unique non-profit organization, which through sponsorship and volunteerism, is able to direct 100 percent of total gross fundraising efforts to breast cancer research. The organization’s name was chosen to honor a dear friend, Terri Brodeur. Terri presented with Stage IV breast cancer in 2003. Effective treatment options did not exist to help Terri, and after a two-year battle she succumbed to the disease leaving behind a beloved husband and three young children.