the 2015 Rays Of Hope Walk for the Cure Survivor's Photograph
Please see the article concerning $3.5 million grant to fund research on breast cancer risk and environmental exposure to common chemicals available on the Baystate Health Website.
Read articles featuring our work done involving our Researchers and Partners:
The Rays of Hope Center for Breast Cancer Research is inviting research proposals
Submissions addressing two broad categories of research are encouraged. Mechanistic studies are needed to identify how to intervene to prevent and treat breast cancer more effectively. Behavioral studies are equally important as they have the potential to improve the lives of breast cancer survivors as well as identify links to mechanisms driving susceptibility and carcinogenesis. Studies examining how environmental/lifestyle exposures alter cellular metabolism, inflammation, epigenetic changes that promote malignancy are of keen interest as the results can guide lifestyle choices and clinical decisions. Studies that utilize the patient-derived cells and tissues curated by the Biospecimen Resources and Molecular Analysis Core at the PVLSI are a priority as these may more accurately reflect the diversity of the disease in women. More fundamental studies will also be considered where they fill a gap in knowledge or address technical advances that presently limit research. Projects designed to improve care and outcomes for breast cancer patients may include modifications of diets or exercise to speed recovery for after treatment. Collaborative studies among investigators using a common set of resources (patients or tissues) to examine multiple endpoints would be an especially productive use of the grant funds that are available. Therefore, investigators with complementary interests are especially encouraged to submit shared projects or note the overlap among independent submissions. Funding requests should be limited to projects feasible for <$25,000/year for 1-2 years.
Fall 2015 Annual Report ROHCBCR
The Rays of Hope Center for Breast Cancer Research (ROH CBCR), co-directed by D. Joseph Jerry, PhD and Grace Makari-Judson, MD, was created in 2011 to build an integrated framework for breast cancer research. The goal was to create the infrastructure to provide patient characteristics and tissue specimens to researchers to expedite research on current problems facing clinicians and patients. The ROH CBCR includes a Review Board for scientific oversight and an Advocacy Council to provide breast cancer advocates a direct voice in deciding research priorities.
- The Breast Research Registry (http://pvlsi.org/breast-research-patient-registry) was developed as the backbone to the research endeavors.
- Over 470 women have contributed lifestyle interviews and access to their tissues in an effort to build a "portrait of breast cancer in Western Massachusetts". With this success we anticipate reaching our initial goal of 1,000 women in 2017.
- The Registry provides a clear picture and dynamic view of the progress and gaps for breast cancer in Western Massachusetts.
The Center has funded a total of 14 projects totaling $693,446 during the past 3 years to investigators at UMass Amherst, Pioneer Valley Life Sciences Institute (PVLSI) and Baystate Medical Center. The rising prevalence of metabolic disorders such as obesity and type 2 diabetes and associations with increased risk of breast cancer and poorer outcomes caused us to focus the resources of the PVLSI and the Center on these relationships. Preliminary information from the research has been used to apply for larger grants from other sources (see $1 million award below). Two projects have already led to publications crediting ROH. While projects are ongoing, summaries of selected studies provide the breadth of the work as well as the extent of the challenges in understanding breast cancer.
Sallie Schneider: High fat diet-induced metabolic disorders and the role they play in the development of breast cancer
- Dietary fat intake has been linked to both increased incidence of breast cancer and more aggressive disease. However, these associations have been challenging to understand because it is clear that obesity alone is not sufficient to cause breast cancer. Drs Schneider and Gauger (PVLSI) used mice to determine if obesity may influence the behavior of normal cells in the mammary gland when Sfrp1,a gene that regulates normal cell growth, is deleted. They found that obesity dramatically impaired normal cell protective signals when the Sfrp1 gene was not functioning (http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0078320). They are following up this work to determine if obesity increases the incidence of mammary tumors in mice that lack proper expression of this gene.
- Katherine Reeves: Relation of Bisphenol-A in breast adipose tissue to breast cancer
- Bisphenol-A or BPA is found in a host of plastic products. This chemical can act like estrogens and can leach into both foods stored in containers and into soil and water. Large-scale studies of urine samples revealed a wide range of exposures among women in the US. However, no studies have examined the levels of BPA found in breast tissue where it could act to promote growth of cancer cells. Dr. Reeves (Department of Biostatistics & Epidemiology, UMass) is using tissue donated by women enrolled in the ROH Breast Research Registry to determine the exposures of women in Western Massachusetts. As BPA can accumulate in fat tissue, the association of levels with Body Mass Index (BMI) is a key feature of the study. She has collected samples from 10 women without breast cancer and 25 women with cancer. The results are expected in the coming months.
- Zhenhua Liu: Wnt-signaling as a mechanism by which obesity modulates breast tumorigenesis
- The "wingless" mutation was discovered in fruit flies in the 1970's. This proved to have a profound impact as the proteins, collectively known as the Wnt signaling pathway, represent one of the critical causes of cancer. Obesity in rodents can cause this pathway to be stimulated and promote growth and metastatic behavior of cancer cells. Drs Liu (Department of Nutrition, UMass) and Schneider (PVLSI) are collaborating to examine whether Wnt signals differ among women with a high BMI and are testing a drug in obese rodents to limit the Wnt signals and decrease tumor growth. Support from Rays of Hope contributed to a recent publication from his lab (http://jn.nutrition.org/content/early/2014/11/12/jn.114.199117). We look forward to their continued success in the second year of their grant.
- Karen Dunphy: Regulation of proliferation and surveillance by estrogen receptors
- Fat cells in the breast can make their own estrogen, therefore, it is important to determine if there are differences among women who have high and low BMI. Estrogens have paradoxical roles in the breast. Lifetime exposures can increase the likelihood of breast cancer, but the high levels during pregnancy reduces the lifetime risk among women and has been confirmed in rodents. Dr. Dunphy's work suggests that these opposing actions of estrogens are carried out by 2 distinct estrogen receptors. She is testing whether compounds that preferentially target the estrogen receptor beta (ERb) can selectively engage the protective gene surveillance pathways. The preliminary data supported by ROH contributed to the over $1,000,000 award from the Department of Defense Breast Cancer Research Program (http://cdmrp.army.mil/bcrp/awards/14breakthroughawards_L2.shtml) to Drs Dunphy and Jerry (Dept of Veterinary & Animal Sciences, UMass) for the next 3 years. For the studies she selected a drug that can be rapidly adapted for breast cancer treatments because it has already been through Phase 2 clinical trials for another disease. Therefore, success could lead to fast-track use in breast cancer.
- Barry Braun: Differentiating fasting from post-prandial hyper insulinemia in modulating biomarkers for breast cancer
- Fasting levels of glucose and insulin are measured commonly in patients as it provides a measure of type 2 diabetes. As insulin can increase growth of breast cancer cells, insulin levels can have a profound impact. However, >50% of insulin secreted throughout the day is in response to meals. Therefore, it is possible that fasting insulin levels are within normal ranges but individuals have extended high levels of insulin after meals. Dr Braun (Department of Kinesiology, UMass) and colleagues have initiated studies to determine (i) if insulin after a meal may provide a more accurate reflection of the daily exposures and (ii) if modest exercise can reduce the daily exposures to insulin. This work has the potential to dramatically revise the clinical management of patients. Dr. Makari-Judson (Baystate Medical Center) and Dr Walker (College of Nursing, UMass) are also planning a parallel study to determine if activity monitors can be used to help patients manage fatigue and limit the swings in insulin to improve health and reduce the risk of breast cancer recurrence.
ROH Research Update September 2015
New strategies for advanced hormone positive breast cancer
Seventy-five percent of breast cancer is hormone receptor positive, meaning that the cancer growth is influenced by estrogen and that drugs that keep estrogen away from the tumor cells are important in treatment. Despite use of these drugs, however, some women will develop progressive cancer often due to the cells becoming resistant to endocrine therapy.
There are many ways that the cancer cells may develop resistance to previously effective strategies, but thankfully, several new drugs help to overcome this.
In women with metastatic breast cancer, palbociclib, (IBRANCE®) a pill which inhibits a pathway known as cyclin-depent kinase, increases the efficacy of hormone treatments like the aromatase inhibitor, letrozole (FEMARA®). Because the addition of palbociclib significantly improved the length of time a woman would be free from progressive cancer, the drug gained fast track FDA approval earlier this year. Side effects of palbociclib include low white blood cell counts and fatigue and concerns include the high cost of the drug.
Another medication effective in overcoming resistance and enhancing the effect of hormone treatments is called everolimus (AFINITOR®). This pill works by inhibiting an important growth pathway known as mTor and is used in combination with other endocrine treatments. Concerns include a common side effect of mouth sores, a rare lung change and high cost. The pill is approved for use with aromatase inhibitors and frequently recommended in women with metastatic cancer, where it has been shown to delay the progression of cancer. Because of its benefit in women with metastatic cancer, it is currently the focus of clinical trials exploring whether or not its use in early stage cancer can prevent a recurrence in the first place. A clinical trial available at Baystate Medical Center, tests whether or not use of everolimus in combination with adjuvant hormone medication in women at high risk of recurrence can reduce the likelihood of developing metastatic cancer.
Old drugs may have a new role. Estrogen in high doses has been used in the past to treat metastatic breast. A hormone strategy to include possible use of estrogen to sensitize cancer cells to the effects of anti-estrogen aromatase inhibitor drugs is the subject of new clinical trials.
Paying it Forward: How to be a Breast Cancer Advocate
This year’s ROH Survivor’s Day featured an interactive panel discussion which included ROH founder Lucy Giuggio-Carvalho, research advocate and former ROH Chair, Anna Symington, and ROH Center for Breast Cancer Research (CBCR) co-directors, Drs Joseph Jerry and Grace Makari-Judson. Forty-five breast cancer survivors and advocates participated in live polling using an audience response system to query attitudes towards advocacy and research.
Advocates include community educators, fundraisers, lobbyists and research advocates who influence the direction of breast cancer research. Dr Makari-Judson explained that the ROH CBCR Advocacy Council was established to provide our community with a direct voice in deciding research priorities and to promote research advocacy by reviewing, providing perspective and influencing research proposals .Advocates have gained experience in reviewing grants and have been named as collaborators on grants. Dr Jerry reviewed the increasing demand for lay advocates to be included in grant proposals. In fact, any grant proposal for more than one million dollars requires an advocate to be involved. Lack of an advocate on a grant reduces the likelihood of success in obtaining funding. Anna Symington shared her experience as an advocate on a recent Department of Defense grant that resulted in an award of over $1,000,000. Advocates are currently listed on other large grants awaiting review. These represent the important role that advocates play in both research and the community.
The answers are helping organize leaders to action. Drs Jerry and Makari-Judson will be organizing training for individuals interested in serving as research advocates. Two questions from the session and the replies are shown below. We are pleased to see the endorsement of this newsletter as a trusted source of information. Most rewarding however, is the power of an organization like ROH, as more that a walk but a source of community involvement, education and inspiration.
Endocrine treatment: includes tamoxifen and aromatase inhibitors
Aromatase inhibitor: Endocrine treatment for postmenopausal women includes anastrazole, exemestane and letrozole
Patient registry provides scientists and clinicians unique view of breast cancer.
Researchers uncover the biological mechanisms that impact the treatment, prevention of breast cancer.