IBC Research Grants Awarded

Dr. Robert J. Schneider of New York University, 2015 Grant Recipient

The Inflammatory Breast Cancer Research Foundation is honored to support the work of Dr. Robert J. Schneider with our 2015 research grant for $40,000. Dr. Schneider’s project will build on his research identifying potential therapeutic targets in inflammatory breast cancer (IBC) following neoadjuvant chemotherapy. Thirty percent of IBC patients have metastatic disease at diagnosis and another thirty percent have progression to mets during the course of their disease. This metastatic spread can be particularly difficult to treat and more research is needed to identify therapeutic targets. Too little research is focused on metastatic disease leaving this patient population with few options.

Dr. Schneider is not new to the IBC community. This is Dr. Schneider’s second grant from our organization. He received a grant in 2010 and continues to be a leader in translational IBC research working with an outstanding group of collaborators. He has numerous publications to his credit and has had a special interest in understanding the molecular underpinnings of IBC. Dr. Schneider serves as Associate Dean in the Office of Therapeutics Alliances, is Co-director of the Breast Cancer Program and Albert Sabin Professor of Molecular Pathogenesis at NYU School of Medicine.

Our thanks to our Medical Advisory Board for reviewing the proposals and guiding the grant process. With high ranking and comments like, “tightly focused…potential for clinical value….proven target and excellent track record of PI [principal investigator],” Dr. Schneider stood out as the winning candidate.

The focus of our 2015 grant, metastatic triple negative IBC, is a particularly challenging form of the disease. This is an area of high interest for the Milburn Foundation whose generous support will help fund this work.
Photo of Doctor Mark Dewhirst

Mark Dewhirst, DVM, PhD, 2013 Kathleen Livingston Memorial Grant Recipient

Mark Dewhirst, DVM, PhD., has been chosen to receive $50,000 to support the research, “HIF-1 driven therapeutic resistance mechanisms in chest wall recurrences of inflammatory breast cancer (IBC)”. The Inflammatory Breast Cancer Research Foundation is pleased to fund this important research with the potential, if successful, to move quickly to improve patient care and outcomes.

Dr. Dewhirst is Co-Director, Radiation Oncology/Imaging Program, Gustavo S. Montana Professor of Radiation Oncology in the School of Medicine, and Professor of Pathology at Duke University’s Duke Translational Medicine Institute.

About this grant: September 20, 2011, the Inflammatory Breast Cancer Research Foundation lost an amazing research advocate and dynamic friend. Kathleen was petite in frame but a giant when it came to her passion to end breast cancer. As her initial inflammatory breast cancer began to spread across her chest, she sought out clinical trials to try and contain the disease so she could maintain her active lifestyle. As is often the case the skin metastasis defied containment and would soon flare and Kathleen would search for yet another new treatment option, again and again. Until the disease took her life, Kathleen was remained a strong voice for quality research and clinical trials.
Photo of Doctor Milan Radovich

Milan Radovich, PhD, Assistant Professor of Surgery at Indiana University School of Medicine, 2012 Grant Recipient

Dr. Radovich has been chosen to receive grant funding from the Inflammatory Breast Cancer Research Foundation. Dr. Radovich, and his lab, have been working with Dr. Bryan Schneider on a next-generation sequencing project funded in 2009 by the Inflammatory Breast Cancer Research Foundation and the Milburn Foundation. Since the start of that project Dr. Radovich has completed his PhD and has a faculty position with the university and a lab next door to Dr. Schneider.

Dr. Radovich’s lab is focusing on the use of next-generation sequencing to identify new therapeutic targets for the treatment of inflammatory and triple negative breast cancers.  Having access to the Komen Tissue Bank at Indiana University allows Dr. Radovich to compare next-generation sequencing findings in cancers with those data from sequencing normal breast tissue.  Little is known about “true normal” breast tissue making it important to compare potential therapeutic targets found in cancerous breast tissue to those found in normal breast tissue. It’s important to identify appropriate biomarkers for treatment that can be measured. Clinical trials that match patients to treatment based on expressed biomarkers will allow translational research advances more quickly and benefit patients.
Photo of Doctor Deborah Silvera

Deborah Silvera, PhD, Receives 2012 Research Award

In recognition of her outstanding work, the Inflammatory Breast Cancer Research Foundation has awarded Deborah Silvera, PhD, Research Assistant Professor, New York University School of Medicine, a grant to continue her study of triple negative inflammatory breast cancer (TN IBC). Dr. Silvera presented a poster at this year’s San Antonio Breast Cancer Symposium focusing on mRNA translation to enhance the radiosensitivity of IBC stem cells. Her research has high translational potential, moving from bench to bedside to benefit patients. In spite of dedicated research in recent years little progress has been made, especially in TN IBC, to improve overall survival. The statistics are a painful reminder of the need to fund quality research that will change those numbers. We’ve asked Dr. Silvera to share, in lay terms, about her research for our readers. Here is that summary.

“At least 35% of IBCs are triple negative (TN) breast cancers, a subtype that has proven particularly resistant to existing therapies. There has been little progress in increased survival for IBC patients for the past two decades. Despite progress in the standard of care for IBC, overall survival remains low, (approximately 30%, with an average 45% 5-year survival and a median 2.5 year disease-free survival post-treatment,) thus new therapies or therapies that will synergize with existing treatments are sorely needed. The current standard of care in the treatment of IBC is combined-modality treatment consisting of neo-adjuvant systemic chemotherapy, with or without radiation therapy (RT), followed by surgery and adjuvant systemic chemotherapy. Radiotherapy is an important component of tri-modality therapy for IBC, which improves disease-free and overall survival when given concurrent with or following chemotherapy. An attractive target for therapy in IBC and other cancers is the inhibition of protein synthesis, this work tests the hypothesis that control of protein synthesis is critically required for progression and maintenance of IBC and, more importantly, the cancer stem cells within IBC tumors, which are likely responsible for recurrence after remission, invasion and metastasis, and that inhibition of translation could lead to radio-sensitization of IBC tumors and cancer stem cells. The availability of several drugs in different stages of development targeting eIF4F components provides us with a rapid way to test the possibility to sensitize IBC tumors to radiotherapy in anticipation of these inhibitors entering the clinic.”

The Inflammatory Breast Cancer Research Foundation is dedicated to supporting quality research that will both increase knowledge of IBC and improve survival for those currently diagnosed. Dr. Silvera’s research meets both these criteria, focusing on an IBC sub-type with unique and unmet needs.
Photo of Doctor Heather Cunliffe

Heather Cunliffe, PhD, Receives Additional Funding for 2012 Triple Negative IBC Research

The Inflammatory Breast Cancer Research Foundation is pleased extend additional grant funding to Dr. Heather Cunliffe, of Translational Genomics (TGen), Phoenix, AZ, to continue her study of triple negative inflammatory breast cancer (TNIBC).

Dr. Cunliffe received a grant of $50,000 in 2011 to pursue molecular characterization of TNIBC. In a recent conversation Dr. Cunliffe shared her excitement about this research and her hopes to publish data in the coming months.

Our thanks to Dr. Cunliffe for her diligence, dedication, and desire to improve the lives of those facing inflammatory breast cancer through quality research. Important research like this, by Dr. Cunliffe is only possible through the continued support of our generous donors.
We asked Dr. Cunliffe to share a overview of her research and future plans with this added funding.

“Our 2011 proposal funded by IBCRF addressed a significant technical challenge faced by researchers investigating the molecular underpinnings of IBC; that IBC does not commonly present as a solid mass, but instead as diffuse clusters of tumor cells throughout the breast and dermal lymphatics. This is a confounding factor for genomic investigations of IBC. Funding from the IBCRF allowed us to leverage novel technology developed at TGen that would overcome this barrier. We were successful in isolating purified populations of IBC tumor nuclei away from normal cells of breast tumor specimens. 10 purified IBC tumor samples were subsequently profiled with technology called aCGH, which identifies cancer-specific changes in the genomic landscape at the DNA level. All 10 tumors were of the “triple negative” subtype. At least 5 cancer pathways were identified as strong candidate drivers of disease biology in more than one case, and druggable targets identified for each pathway. These observations are being functionally validated in 2 laboratory cell line models of triple negative IBC.

To build a successful extension of this study with the intent to accelerate translation of our findings for clinical utility, we wanted to take full advantage of the remaining successfully purified IBC tumor DNA samples, and sequence the genome from one of these patients. We were fortunate that one of the IBC tumors profiled has a matched sample of peripheral blood from which germline (constitutional) DNA can be obtained. By comparing the tumor DNA sequence with the non-cancerous germline DNA sequence from the same patient, we will be able to define tumor-derived aberrations at maximum resolution, shedding additional light on the likely drivers of malignant progression. Importantly, with the recent availability of breast tumor sequencing data from The Cancer Genome Atlas Network (CTGA), cross comparison of our findings is likely to reveal IBC-specific aberrations that are not present in triple negative non-IBC, and frequently present in triple negative IBC. TGen is a center for excellence in application of the ‘next generation’ sequencing technology to be utilized. Thanks to the ongoing support of the IBCRF, and the Milburn Foundationwe are enthusiastic to move forward with this study.”
Photo of Doctor Beth Overmoyer

Beth Overmoyer, MD, Receives $50,000 Grant from the Inflammatory Breast Cancer Research Foundation in 2011.

For the first time in the history of the foundation, two grant awards were made in 2011. A $50,000 grant was awarded to Dr. Beth Overmoyer of Dana-Farber Cancer Institute to pursue her research project, “Validation of Jak2 as Novel Therapeutic Target in Triple Negative Inflammatory Breast Cancer.”

Dr. Overmoyer explained that “We are geared to correlate the association of upregulated pSTAT3 activity and IBC in the laboratory and translate this understanding into the clinic by using JAK2 inhibition as a means of downregulating pSTAT3. This appears to be a very active method for cancer survival among triple negative breast cancers, and IBC in general, therefore our clinical trial will provide proof of concept that JAK2 inhibition is effective in this virulent disease, and should be part of standard treatment.”

A medical oncologist focusing on the treatment of breast cancer, Dr. Overmoyer is also an Assistant Professor of Medicine at Harvard Medical School. In addition to these duties, Dr. Overmoyer heads the team of specialists for the Dana-Farber/Brigham and Women’s cancer Center’s IBC Program.

Funding for the 2011 grants was made possible through a collaboration of the Inflammatory Breast Cancer Research Foundation and the Milburn Foundation.
Photo of Doctor Heather Cunliffe

Heather Cunliffe, PhD, Head of TGen™s Breast & Ovarian Cancer Research Unit, Recipient of 2011 Inflammatory Breast Cancer Research Foundation Grant

Press Release:
PHOENIX, Ariz. Sept. 7, 2011 The Inflammatory Breast Cancer Research Foundation (IBCRF) has awarded $50,000 to the Translational Genomics Research Institute (TGen) to discover the genetic origins of this rare and most deadly form of breast cancer.

“Unlike other types of breast cancer, Inflammatory Breast Cancer (IBC) is very often misdiagnosed, and rapidly progresses to an advanced stage,” said Dr. Heather Cunliffe, Head of TGen’s Breast & Ovarian Cancer Research Unit. “No one knows what causes IBC and what drives the aggressive nature of this disease,” Dr. Cunliffe said. “You can wake up one morning and out of the blue your breast will be twice its normal size, red and inflamed with full blown Inflammatory Breast Cancer.” As soon as it is diagnosed, patients typically start chemotherapy, even before surgery, to try and reduce the rapid spread of the disease, Dr. Cunliffe said. Still, there is no cure for IBC, which represents less than 5 percent of all breast cancers.

TGen’s interest in IBC began in 2006 after several Phoenix-area women who developed the disease urged the institute to conduct research. “They shared the work of the Inflammatory Breast Cancer Research Foundation and suggested we might work together,” said Ginny Mason, Executive Director of the IBCRF. Since that introduction, there have been many opportunities to partner with Dr. Cunliffe in her research. Dr. Cunliffe’s outstanding grant proposal, High-Resolution Molecular Pathology to guide Rational Therapeutic Approaches for Triple Negative Inflammatory Breast Cancer, addresses an important aspect of inflammatory breast cancer research, and hopefully will lead to identifying new targets for therapy.
Funding for this grant was made possible through a partnership between the IBCRF and the Milburn Foundation, Mason said. The $50,000 award will enable TGen to analyze DNA samples from IBC tumors, to look for underlying genetic similarities that may indicate a therapeutic vulnerability. TGen researchers will zero in on the triple-negative (TN) form of IBC. Triple-negative breast cancers are those that do not express clinically significant levels of estrogen receptor (ER), progesterone receptor (PfR) or human epidermal growth factor 2 (HER2). “It is critical that we discover the molecular and biologic underpinnings driving the highly aggressive behavior of TN-IBC tumors,” Dr. Cunliffe said.

A significant confounding problem in IBC research is that cells within an IBC tumor are mostly diffuse throughout the breast, mixed with normal cells and a significant number of immune system cells, Dr. Cunliffe said. “This makes isolation of tumor-specific DNA samples for research exceedingly difficult,” Dr. Cunliffe said. TGen’s study will leverage a technology developed in the laboratory of Dr. Michael Barrett at TGen that solves this problem, allowing us to purify and examine TN-IBC DNA accurately at high resolution without contamination of DNA from normal healthy cells.

Dr. Cunliffe said she hopes to quickly translate TGen’s laboratory findings into new therapeutic approaches that will benefit TN-IBC patients.
Photo of Doctor Robert Schneider

Robert J. Schneider PhD, NYU Medical Center, Recipient of 2010 Inflammatory Breast Cancer Research Foundation Grant

Through a generous gift from the Milburn Foundation, the Inflammatory Breast Cancer Research Foundation has awarded a $50,000 grant to Robert J. Schneider, Ph.D., of New York University, Langone Medical Center.

Dr. Schneider’s project, Translating mTOR and Translational Regulation to Therapy in Triple Negative Inflammatory Breast Cancerwas chosen from a pool of outstanding applications. “It’s difficult to choose just one project for funding when they are all worthwhile and important projects,” said Executive Director Ginny Mason. Dr. Schneider’s proposal received high marks for relevance and for the translational potential, moving from “bench to bedside” to impact patient treatment.

The grant process involved inviting specific scientists to respond to a request for applications (RFA). Once those materials were received they were reviewed by the Medical Advisory Board and the Board of Directors of the Inflammatory Breast Cancer Research Foundation. Following the review comments were evaluated and one project was chosen to receive the 2010 grant. The announcement of the 2010 grant recipient was delayed to 2011 due to unforeseen circumstances.

Dr. Schneider and colleagues have focused much of their research time and effort in the study of inflammatory and locally advanced breast cancer. Last year’s publication by Dr. Schneider, Essential Role for eIF4GI Overexpression in the Pathogenesis of Inflammatory Breast Cancer, created quite a stir in the inflammatory breast cancer community. The media presented this research as discovering the gene for inflammatory breast cancer (IBC), when in actuality it is a translation factor. It’s important to understand that eIF4GI is a translation factor overexpressed in most IBCs, resulting in its unique pathogenic properties. Understanding this mechanism can aid potential control of the disease.

Dr. Schneider and colleagues have developed a unique understanding of the importance of translational control in the development and progression of inflammatory breast cancer (IBC). This understanding can now be used to help develop novel therapeutic and tailored approaches for IBC in general and triple negative IBC in particular. This research group has identified and developed innovative, targeted and triple negative IBC-specific approaches for treatment of this disease. With this grant, Dr. Schneider will use these insights in animal models to rapidly develop targeted therapeutic intervention, leading to a future pilot Phase I/II clinical trial.

The Inflammatory Breast Cancer Research Foundation is excited to join with Dr. Schneider and colleagues in this important research venture targeting the needs of those patients diagnosed with triple negative inflammatory breast cancer.
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Bryan Schneider, MD., Recipient of 2010 Inflammatory Breast Cancer Research Foundation Grant

Women with a relatively rare but aggressive form of breast cancer may benefit from a unique tissue bank of normal breast tissue at the Indiana University Melvin and Bren Simon Cancer Center.

Bryan Schneider, M.D., and doctoral student Milan Radovich will study the underlying molecular underpinning of inflammatory breast cancer using cutting edge technology called Next Generation Sequencing with the support of a $50,000 grant from the Inflammatory Breast Cancer Research Foundation and the Milburn Foundation partnership. This work will capitalize on the ability to compare genetic abnormalities against normal breast tissue.

Press Release, August 9, 2010, Indianapolis:
Bryan Schneider, M.D.
Assistant professor of medicine
Researcher at the IU Simon Cancer Center
Indiana University Physician Receives Funding for Rare, Aggressive Breast Cancer Research
Women with a relatively rare but aggressive form of breast cancer may benefit from a unique tissue bank of normal breast tissue at the Indiana University Melvin and Bren Simon Cancer Center.

Bryan Schneider, M.D., and doctoral student Milan Radovich will study the underlying molecular underpinning of inflammatory breast cancer using cutting edge technology called Next Generation Sequencing with the support of a $50,000 grant from the Inflammatory Breast Cancer Research Foundation and the Milburn Foundation partnership. This work will capitalize on the ability to compare genetic abnormalities against normal breast tissue.

“To identify the critical molecular changes that distinguish normal from malignant, and to detect the earliest indication of the transformation, researchers must be able to study normal breast cells,” said Dr. Schneider, the recipient of the IBC grant. “Since 2005, hundreds of women have donated tissue to the Susan G. Komen for the Cure Tissue Bank® at the IU Simon Cancer Center to make it possible for researchers to identify abnormalities in cells. We are hopeful that the information contained in the Bank will direct scientists to cures for the many forms of breast cancer.” Dr. Schneider is an assistant professor of medicine at Indiana University School of Medicine and a researcher and clinician at the IU Simon Cancer Center.
Photo of Doctor Diane Palmieri

Inflammatory Breast Cancer Research Foundation Awards Grant to Study Brain Metastasis of IBC (Oct 2009)

Diane Palmieri, Ph.D, National Cancer Institute scientist in the Laboratory of Molecular Pharmacology, Women’s Cancers Section, has been chosen to receive a grant from the Inflammatory Breast Cancer Research Foundation. The award, in support of her proposal Development of Mouse Models of Inflammatory Breast Cancer Brain Metastasis, will seek to further the understanding of progression of this unique, aggressive form of breast cancer.
Inflammatory breast cancer, a less common and potentially deadly form of breast cancer, remains a poorly understood disease. While general breast cancer research has provided some insight, specialized study of inflammatory breast cancer and its aggressive metastatic nature is essential. Dr. Palmieri’s proposal was selected from a pool of outstanding submissions receiving high marks for its relevance and translational potential.
Dr. Palmieri is a Co-PI on a Department of Defense Center of Excellence Award entitled Studies Directed toward the Eradication of Brain Metastasis of Breast Cancer. A comprehensive website has been developed to disseminate research results from this exciting project (http://www.brainmetsbc.org.) Advocates are an integral part of this Center of Excellence (COE) project and are responsible for developing the website, providing a resource for those seeking information on brain metastasis of breast cancer. Dr. Patricia Steeg, Head of the Women’s Cancer Section and long time friend and supporter of the Inflammatory Breast Cancer Research Foundation, has assembled an amazing group of researchers and advocates to escalate the development and implementation of new treatments for patients dealing with brain metastasis from breast cancer.
In addition to her research, Dr. Palmieri is a faculty member of the National Breast Cancer Coalition Fund’s Project LEAD advocate science training program. She gave an outstanding presentation, entitled Understanding Cell Signaling, to Project LEAD graduates attending the San Antonio Breast Cancer Symposium in 2008.
Dr. Palmieri received her B.S. in Biotechnology from Rochester Institute of Technology and her Ph.D. from the University of North Carolina. She began her career in the Women’s Cancer Section in 2002 as a research fellow, moving into the position of staff scientist in 2005. Dr. Palmieri has numerous peer-reviewed publications to her credit and has given poster and other presentations at a variety of cancer venues.
This grant award is made possible through a partnership of the Inflammatory Breast Cancer Research Foundation and the Milburn Foundation. The Inflammatory Breast Cancer Research Foundation, a non-profit incorporated in 1999, is dedicated to facilitating research and raising awareness of inflammatory breast cancer. The Milburn Foundation, a private charitable foundation, was created to support leaders who are making a difference in the fight against critical health care challenges.