Komen Funding Launches One Investigator’s Career as He Works to Prevent Breast Cancer Metastasis to the Brain
Blog post by Jamie Stanford, Ph.D., Komen Scientific Grants Manager
Susan G. Komen has funded over $135 million in research grants for young investigators. These research dollars are vital as funding for scientific research from the U.S. government becomes more limited, cut by more than $1 billion in the past 4 years. Young investigators are some of the hardest hit by funding cuts. In 2014, the National Cancer Institute funded less than one third of the grant applications submitted by young investigators. Taking on novel research ideas and working with fewer resources and years of experience, young investigators typically have lower success rates than senior investigators. Therefore, many are turning to non-government funding agencies like Susan G. Komen to jump-start their careers. To address this issue, Komen has dedicated itself to ‘Sustaining Progress in Cancer Research’ by funding nearly $16 million for young investigators alone in 2014.
Dr. Bisrat Debeb is just one of hundreds of young investigators whose careers were launched from Komen research funding. As a postdoctoral fellow in the laboratory of Dr. Wendy Woodward, Dr. Debeb’s Komen-funded project focused on understanding how small pieces of RNA (ribonucleic acid), called microRNAs, affect breast cancer metastasis to the brain. Under this fellowship, his training and successful results became the foundation for his career.
During his fellowship, Dr. Debeb and his Mentor, Dr. Woodward, developed new models of brain metastasis and discovered that when breast cancer cells express a microRNA called miR-141, they are more likely to spread (metastasize) to the brain. Likewise, reducing levels of miR-141 prevented breast cancer cells from spreading to the brain. Furthermore, they found that high levels of miR-141 in patient’s blood were associated with poor brain metastasis-free survival and low overall survival.
These studies indicate that miR-141 levels in a patient’s blood could be used to monitor cancer progression in patients diagnosed with metastatic breast cancer, and that reducing levels of miR-141 could help prevent metastatic spread to the brain.
Now, in his role as Assistant Professor in the Department of Radiation Oncology at The University of Texas MD Anderson Cancer Center, Dr. Debeb’s research is a continuation of this Komen-funded project. His studies focus on evaluating the therapeutic benefit of reducing miR-141 levels in order to prevent brain metastasis. Dr. Debeb and his colleagues have also begun to more specifically unveil how miR-141 causes breast cancer to spread to the brain.
Dr. Debeb’s contributions to research will bring more hope and options for patients, and his success, which began with data generated from a Komen-funded grant, has opened doors professionally. In fact, he was recently granted the highly competitive National Institute of Health Exploratory/Developmental Research Grant Award. He is also the recipient of the first Junior Investigator Grant from the Inflammatory Breast Cancer Network Foundation. With this new funding, Dr. Debeb will continue to expand upon the project he developed as a Komen postdoctoral trainee. The Komen Postdoctoral Fellowship award “…has been a critical component for my career development and has laid a solid foundation for establishing myself as an independent investigator in the field of breast cancer,” says Dr. Debeb.
Why do some women develop breast cancer and not others? And why do some women develop breast cancer at a much younger age? We know that factors like weight, alcohol consumption and hormone replacement therapy, among others, may affect breast cancer risk. But some women with one or more risk factors will never get breast cancer, while some women with no apparent risk factors will still develop the disease.
These questions prompted Komen grantee Dr. Clarice Weinberg, and her colleagues Drs. Dale Sandler and Lisa DeRoo, to conduct a study on how a woman’s genes and her environment might affect her risk of breast cancer. In 2008, the researchers launched the Two Sister Study, funded by Komen with a 5-year, $1.75 million grant, along with funding from the National Institute of Environmental Health Sciences (NIEHS).
The Two Sister Study builds upon the work of the Sister Study and focuses on women who developed breast cancer at a young age, with the idea that this group of women can help us learn a lot about the genetic and environmental causes of breast cancer. What makes the Two Sister Study unique is that it gathers data from sisters, who share similar genes and possibly environmental backgrounds.
The Two Sister Study enrolled over 1,400 women recently diagnosed with early-onset breast cancer (under the age of 50), 1,700 of their sisters from the Sister Study (who did not have breast cancer), and parents when possible. Participants provided detailed information about family and medical history, diet, occupation, as well as house dust and DNA samples. After collecting hundreds of samples and surveys from study participants, their sisters and families, Dr. Weinberg and her collaborators identified new potential risk factors for young women. Specifically, the research team found that women who were sensitive to certain hormonal changes differed in their risk for early-onset breast cancer.
They found that reduced risk was associated with:
- Fertility treatments to stimulate ovaries when it does not result in pregnancy.
- Night sweats and hot flashes in pre-menopausal women, which are symptoms typically associated with menopause.
- History of pregnancy-associated hypertension (high blood pressure).
- Hormone replacement therapy with estrogen alone.
Dr. Weinberg also found that women who suffered from menstrual migraines were less likely to develop hormone receptor negative breast cancer (estrogen receptor-negative and progestin-receptor negative). Together, these findings suggest that a young woman’s overall response to hormones during the different phases in her life may be related to her risk of developing breast cancer early.
The initial results from the Two Sister Study about a woman’s response to hormones add to our knowledge of breast cancer risk factors and early-onset breast cancer. Data from the study are still being analyzed in efforts to identify other risk factors for breast cancer. “The rich data (we have) developed through this family-based study offers a unique window on little-studied possible mechanisms,” says Dr. Weinberg. Data on genetic mutations that impact early-onset breast cancer will continue to be mined for years to come as scientists continue to identify both genetic and modifiable (e.g. behavioral) factors related to survival and good health in survivors of young onset breast cancer.
The genetic data collected through this research project are now publically available through the NIH’s CIDR dbGap website for researchers to use at: http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000678.v1.p1.
Jack Taylor: Senior Investigator, NIEHS
Dale Sandler: Chief, Epidemiology Branch and Principal Investigator, NIEHS
Lisa DeRoo: Staff Scientist, NIEHS and University of Bergen, Norway
Clarice Weinberg: Chief, Biostatistics & Computational Biology Branch and Principal Investigator, NIEHS Stephanie London: Deputy Chief, Epidemiology Branch and Principal Investigator, NIEHS
Paula Juras: Project Officer, NIEHS
Guest blog by Komen grantee Dr. Lisa A. Newman, MD, MPH, FACS, Professor of Surgery and Director of the Breast Care Center for the University of Michigan in Ann Arbor, Michigan. Dr. Newman has dedicated her career to fighting breast cancer disparities. Named one of the 2012 Michiganians of the Year, she was also featured on CNN’s 2009 documentary “Black in America 2.” She was even called a “Breast Cancer Hero” in the October 2012 issue of Oprah Magazine.
I am honored to celebrate Black History Month by sharing what I have learned over my career as a surgical oncologist studying the many factors that contribute to disparities in breast cancer outcome, especially as they relate to triple negative breast cancer and African ancestry.
When my training as a surgeon first began (more than twenty years ago), it was widely assumed that the higher breast cancer mortality rates observed in the African-American population were completely explained by the more prevalent socioeconomic disadvantages in this community, with its related diagnostic and treatment delays. Unfortunately, these socioeconomic factors persist today, and they undeniably play a major role in causing tragically higher degrees of pain and suffering from breast cancer.
Over the past few decades, however, we have also made tremendous advances in understanding breast tumor subtypes, and we have learned that African Americans face an increased risk for being diagnosed with more aggressive breast cancers, such as triple negative breast cancer (TNBC). Today, the study of breast cancer disparities related to racial/ethnic identity includes investigations of hereditary genetics and tumor genomics, as well as socioeconomic and health care access inequities.
Although my clinical responsibilities are based in Michigan, my research has led me to sub-Saharan Africa, to learn about the breast cancer burden of women that have shared ancestry with African-Americans dating back to the colonial slave trade era. I have had the privilege of working with the oncology team at the Komfo Anoyke Teaching Hospital in Kumasi, Ghana, for nearly ten years.
What we have learned is striking: similarities indeed exist between the breast cancers identified in Ghanaians and those detected in African Americans. TNBC accounts for approximately 15% of the tumors seen in White American and European patients; approximately 30% of those in African Americans, and the majority of those seen in Ghanaian breast cancer patients. Funding from Susan G. Komen has enabled us to document these patterns and has also supported our studies of novel patterns of expression for molecular markers that are associated with mammary stem cell and TNBC progression, such as EZH2 and ALDH1. This work has also led to a platform for creating a library of patient derived xenografts (PDXs) from TNBC patients of internationally diverse backgrounds. These PDXs are an exciting model for studying the biology of TNBC and treatment sensitivity that can more easily be studied by many scientists for years to come.
Our work at Komfo Anoyke has also provided wonderful opportunities for academic and educational exchange experiences, strengthening our efforts to improve breast cancer survivorship on both sides of the ocean. Students and trainees from the University of Michigan routinely participate in our research trips to Ghana, which have been partly funded by Komen, and our Komfo Anoyke colleagues come to Michigan regularly to participate in research projects and to learn about the latest strategies in breast cancer treatments. One of the Komfo Anoyke surgeons is currently nearing completion of her PhD work in Cancer Biology at the University of Michigan, after which she will return to Ghana to establish an independent Kumasi-based laboratory.
We have also invested in a state-of the-art, internet-based telemedicine conference facility at Komfo Anoyke. This program allows us to host ongoing live weekly meetings and educational conferences, uniting our teams in Michigan and at Komfo Anoyke as one, overcoming the thousand-mile geographic separation to review cases and strategize the treatments that will best benefit our patients.
Our international breast cancer research program now works with three different hospitals in Ghana, and we are also in the process of obtaining approvals for participating sites in Ethiopia, India, and China.
Research has brought us many clues about the origins of breast cancer, and why it may affect some groups of women differently. But there is still much to learn about the biology of breast cancer that affects women of African Ancestry. I am pleased that our work, which began in Michigan, continues to be strong in Ghana and is now spreading to other African countries.
Read a recent Komen Perspectives article on triple negative breast cancer (TNBC).
Learn more about Komen’s work on breast cancer disparities in our Mission Fast Facts.
Guest blog from Komen Scholar Dr. Ann Partridge, Associate Professor, Department of Medicine, Harvard Medical School; Director, Program for Young Women with Breast Cancer, Susan F. Smith Center for Women’s Cancers; Director, Adult Survivorship Program Dana-Farber Cancer Institute
A breast cancer diagnosis can be a really scary thing. Even though doctors and statistics can reassure women that most will be ok in the long run, many women worry that, “they were the one that got breast cancer, and they may be the one that hears from it again.” And, understandably, they may want to do every possible and reasonable thing they can to reduce that chance.
One potential option for reducing the risk of breast cancer that has received increasing attention in recent years is “contralateral prophylactic mastectomy” or CPM. CPM is a procedure where both breasts are removed (bilateral mastectomy) even though breast cancer is only in one breast (unilateral breast cancer).
Rates of CPM have increased dramatically in the past decade, drawing the attention of doctors who care for women with breast cancer, as well as researchers trying to understand this trend. Generally speaking, is CPM good for women in the long run? Or is there something we should do to reverse this trend? There are a number of reasons women may choose to remove or not remove a healthy breast, and women should understand the risks and benefits of CPM in order to make the best decisions for their lives.
So, what has research shown us so far? First, and most importantly, studies have shown that, in the long run, removing a woman’s healthy breast when she has breast cancer in the other does not improve overall survival. This is because the vast majority of breast cancer survivors will not develop a new breast cancer in the other breast (which is essentially the only scenario a woman is preventing when she removes the healthy breast). Exceptions could include women with a known genetic predisposition to breast cancer like those with a BRCA 1 or BRCA 2 gene mutation, whose risk of a new breast cancer occurring in the other breast is higher.
Further, a woman who has been previously diagnosed with breast cancer is generally being watched closely with more frequent follow-up screenings. So, even if a second breast cancer develops in the healthy breast, it is usually caught early, and she will be treated quickly.
Many women I see in my clinic that are making surgical decisions think they are reducing the chances that their breast cancer will come back by removing the other, unaffected breast. But this is not the case. For most women, if a breast cancer is going to come back, it is usually not to the other breast. As women learn this, they often think differently about the idea of removing their healthy breast.
Another thing to consider is that any potential decrease in risk resulting from CPM does not decrease the possibility of the primary breast cancer spreading or recurring elsewhere in the body (metastasizing).
There are a few key things women should know about mastectomy as well. Although mastectomy is a safe procedure and major complications are rare, there are potential negative consequences, including cosmetic concerns, and other potential long-term effects such as numbness of the chest skin, swelling, chronic pain and decreased motion of the upper arm. Given most women also opt for reconstruction, it’s important to consider the extended recovery time, added surgical complications, and decreased strength or function due to muscles being moved or stretched.
On the other hand, women have shared a number of reasons with us that cause them to consider CPM. For some, the idea of having any chance of a new breast cancer in their healthy breast is very anxiety-provoking, as is consideration of follow-up mammograms to screen for new breast cancer in the future. They would prefer to never have to deal with that again and are willing to undergo CPM to prevent it. Cosmetic concerns may also be a driver, with the desire to have two reconstructed breasts that look similar instead of one treated breast and another natural breast. Although, plastic surgeons today can do much to help recreate a more natural look, ensuring both breasts looks similar and symmetrical.
Recent studies have indicated that fear of recurrence and anxiety are strong predictors of whether women will choose CPM. Improved education and counseling about the risks and benefits of CPM, as well as increased awareness and management of anxiety surrounding breast cancer diagnosis and treatment, are likely to help women understand their risks more fully and make decisions consistent with their preferences and values.
Researchers are working on tools called “decision aids” to help women to make the best decisions for themselves, in conjunction with their doctors, which may be particularly helpful for women going through this difficult process in the future.
For any woman dealing with this decision, it is important to learn the facts and discuss their concerns with their doctors in order to make the best decision. I also always recommend that women take their time to be sure. Sometimes this means waiting to take action with the other breast, because once it’s removed, you can’t put it back on!
Ultimately, this is a very personal decision and women need to be supported with information and emotional support to do what is best for them.
Learn more about BRCA1 and BRCA2 gene mutations.
Learn more about breast reconstruction
Learn more about social support and find a list of support resources.
Twelve years ago, when I walked up to the registration table in St. Louis, Missouri, I signed up to volunteer for the upcoming Race for the Cure in memory of my mother-in-law Carolyn Gill who passed away from breast cancer.
But that was only the beginning. My breast cancer journey continued with my mother, my aunt, and then with my own diagnosis in 2011. No one wants to hear, “I am sorry to tell you, you have breast cancer,” but volunteering and being a part of the Komen St. Louis family made hearing those words so much easier! I reached out to Helen Chesnut, Executive Director of Komen St. Louis, right after my diagnosis because I felt lost. My mother was in the midst of her breast cancer diagnosis (her breast cancer surgery came one month before mine), so she could not be there for me – neither physically nor psychologically. She could not handle both our diagnoses.
Helen was always just a phone call or email away. She was by my side, helping me vet my doctors and navigate the healthcare system. She was the first individual I met who was truly a “survivor and a great advocate.”
Helen was one of the reasons I jumped at the opportunity to bea member of Komen’s Advocates in Science (AIS). I am merely giving back the excellence and servant leadership that was given to me four years ago.
As an AIS member, I have participated as an advocate reviewer in the peer review process that Komen conducts each year as to determine which research grants will be recommended for funding. I am completely in awe of the brilliance in the breast cancer research community. We often hear the daunting breast cancer statistics, especially for African-American women, but being around such brilliant and passionate researchers and advocates showed me that all hope is not lost! I came away from the review process simply excited as a survivor and an advocate.
It is important to me that others, particularly African-American and Hispanic/Latina women, have this same hope if they are diagnosed with breast cancer. My mother’s reaction to her diagnosis is how many women in our community react. She is the rule; not the exception. This
passion drove me to found Supporting Our Sisters International, Inc.. Our mission is to support our African-American and Hispanic/Latina sisters with a message of health, hope, healing and quality care. We are dedicated to improving knowledge and access across the continuum of cancer care, and we are helping women adapt healthier lifestyles in order to help reduce the risk
of breast cancer recurrence. Many studies show that weight gain is a risk factor for breast cancer after menopause, and women who engage in regular physical activity have a lower risk of developing breast cancer compared with women who are sedentary. It is our goal to help create informative change within the breast cancer movement.
The best practices Komen incorporates into its work have been highly influential in how Supporting Our Sisters International carries out our mission. We have incorporated many of the great values learned during my years as a volunteer, through my personal experience, as well as from my experience as one of Komen’s AIS members. I am excited to be a part of the survivor advocacy community – both as an individual and through Supporting Our Sisters International. We are excited to develop and implement new resources for women facing breast cancer, and be a voice for survivors.
It will take all hands on deck to save lives and end breast cancer, and I am honored to be on board!