Following a clinic visit, patient Christina Klawitter (center) thanks Lee Wilke (left) and Samuel Poore for their roles in helping her decide what treatment options would work best for her.
In 2012, the octogenarian’s oncologist urged her to undergo testing for BRCA gene mutations, which now are known to increase an individual’s risks for breast and ovarian cancer. The result set off a flurry of BRCA 1 testing among her relatives.
While Klawitter happily inherited her grandmother’s tenacity, love of life and strong dedication to her family, unfortunately, she also inherited her BRCA 1 mutation.
Klawitter turned to the UW Health Breast Center, part of the University of Wisconsin Carbone Cancer Center (UWCCC). At the center, Klawitter began a journey guided by experts who dedicate their lives to understanding the mechanisms of cancer.
They translate knowledge into state-of-the-art patient care for women with significant risk factors for developing breast cancer, those who have invasive and noninvasive cancers and benign breast conditions, and survivors.
“The center draws upon everything from basic science research in cell biology, immunology and genetics to engineering, medical physics, pharmacology and many other fields,” says Wilke. “We offer patient and family-centered care that includes support services like social work, nutrition, occupational therapy, integrative medicine and palliative care.”
The Path Toward a Personalized Plan
Klawitter’s first stop was the center’s Prevention, Assessment and Tailored Health Screening (PATHS) program, established by Kari Wisinski, MD, a medical oncologist at the Carbone Cancer Center. Through this program, Klawitter met Amy Stettner, a certified genetic counselor in the Oncology Genetics Clinic, who provided her with extensive information about statistics and treatment options.
“I had never heard of BRCA mutations before. Because of my BRCA 1 mutation, my odds of getting cancer were mindboggling – nearly a 50 percent chance of getting ovarian cancer and an 80 percent chance of getting breast cancer,” shares Klawitter, a vibrant mother of two young sons.
Because BRCA 1 mutations cause no health risks in childhood, Klawitter plans to advise her sons, when they reach adulthood, that they each have a 50 percent chance of carrying the trait.
Learning comes naturally for Klawitter, who is the dean of students for Beloit College in Beloit, Wisconsin. As she dug into researching BRCA 1 mutations, her project management style kicked in. She holds a bachelor’s degree in psychology from Beloit College, and a master’s degree in counseling and a doctorate in educational leadership and policy analysis from UW-Madison. She was an assistant dean in the university’s College of Letters and Science before returning to Beloit College two years ago.
The Breast Center has nearly 50 physicians and more than 75 researchers, who each share joint appointments in other School of Medicine and Public Health and UW-Madison departments. Pictured here, front row (left to right): Mark Burkard, Amy Stettner and David Beebe; back row: Howard Bailey, Amy Fowler, Lee Wilke and Michael Gould.
From her home in Stoughton, Wisconsin, Klawitter traveled to the Breast Center’s location at UW Hospital and Clinics within the Clinical Science Center. There is a second Breast Center location at 1 South Park Street in Madison, and Wilke plans to expand the center regionally so patients will be able to access services at other UW Health locations.
“For patients who have risk factors like Christina does, we coordinate evaluations by a geneticist, medical oncologist, surgeon, plastic surgeon and gynecological oncologist,” notes Wilke. “We combine personal care with the newest technology and leading treatment protocols, as well as clinical trials, when appropriate.”
Through a shared decision-making process, the staff helps each patient create a tailored plan. Some may require only ongoing screening or medicines to reduce the risk of cancer, while others gravitate toward surgical options, explains Wilke. Patients who already have cancer may also receive radiation, chemotherapy or both.
In Klawitter’s case, UW Carbone Cancer Center experts encouraged her to address her high risk for ovarian cancer first. She chose to have her ovaries and fallopian tubes removed in April 2013. UW Health physician Stephen Rose, MD, an associate professor of gynecologic oncology, conducted her surgery.
Tools for Informed Decision-Making
Klawitter says that decision was made easier because she and her husband already have children. Then, while undergoing screening mammography and other imaging, Klawitter delved into her next difficult decision.
“I live an active lifestyle, and I am very aware of my health and wellness, including how those things impact the people I love,” reflects Klawitter. “Dr. Wilke was great at sharing tools to gauge my odds and the implications of my choices without trying to sway me either way. She reassured me that I did not have cancer.
“That was encouraging, but nobody can predict what kind of cancer I would possibly get, or when and where it might appear. This was a very personal decision, and I did not want to take any chances that cancer would develop,” she says. “For me, the right solution was to have a preventive bilateral mastectomy with reconstruction.”
Klawitter adds that she appreciated the approach offered by Wilke and Samuel Poore, MD, PhD, a plastic surgeon at the UW Health Breast Center and an assistant professor in the Department of Surgery. In January 2014, Wilke performed Klawitter’s double mastectomy, and Poore and his team began managing a four-month process of breast reconstruction.
“I am happy that I was able to have the surgery when I was otherwise very healthy, fit and ready,” she notes. “Then again, I played the odds with healthy body parts at a young age. That’s a complicated thing to work through emotionally.”
All along, Klawitter had another drive: to donate her tissue for research that will benefit other women.
“Dr. Wilke explained that my breast tissue would be very valuable for research,” says Klawitter. “These are smart, highly motivated people who see the bad effects of these diseases every day. Without contributions of breast tissue, that research would not be possible.”
Using Microenvironments to Study Cancer
Klawitter’s anonymous tissue began a journey into the UW Carbone Cancer Center BioBank, created with funding from the Wisconsin Partnership Program and the National Cancer Institute (NCI). Among the many Breast Center researchers who study patient tissues are Wilke, David Beebe, PhD ’94, Patricia Keely, PhD, Michael Gould, PhD ’77, and Howard Bailey, MD (PG ’90).
Bailey is the interim director of the Carbone Cancer Center, which is Wisconsin’s only such center deemed comprehensive by the NCI.
Beebe and Keely, professors of biomedical engineering in the UW-Madison College of Engineering, work collaboratively with microenvironments in which cancer cells grow and change outside of the human body. They focus on ductal carcinoma in situ (DCIS), which is Stage 0 cancer, including how and why it sometimes transitions into invasive ductal carcinoma.
“While new imaging techniques make it easy to detect DCIS, only some cases will become invasive cancer. A big problem is that physicians have no way to know which patients will get cancer, so they and their patients are left with a dilemma – to treat or not to treat,” Beebe says.
To aid in these and similar queries, Beebe and his team created microfluidic systems in which they grow small numbers of cells in channels the size of hair follicles to simulate tumor growth. The chambers’ environment closely resembles that of the human body.
Keely’s work focuses on factors that appear to help predict whether the DCIS cells – which grow in dense and non-dense tissue – will progress to cancer.
“For years, scientists have studied genetics to learn about DCIS. We are analyzing the microenvironment around breast cells using three-dimensional collagen gels that instruct and affect the DCIS cells,” says Keely, who is collaborating in this work with Amy Trentham-Dietz, PhD, an associate professor in the Department of Population Health Sciences.
“Microenvironments with a lot of collagen drive the cells to behave like cancer,” Keely explains. “If you place normal mammary cells or early-stage cancer cells into non-dense collagen, the cells form ductal structures that behave normally. However, if you place normal or cancer cells in stiff, dense collagen, they behave like cancer by losing their normal architecture, dividing rapidly and becoming invasive.”
Her team theorizes that when collagen aligns like a bundle of uncooked spaghetti noodles – rather than a bowl of cooked spaghetti – it forms “highways” on which the cancer cells travel.
“Our goal is to determine which patients need to be treated aggressively and which could have less aggressive treatment,” notes Keely, who was recently named the chair of the Department of Cell and Regenerative Biology.
With a similar goal, Beebe’s laboratory looks at variations in soluble-factor signaling among cell types.
“We are discovering that reciprocal signaling between the DCIS cells and the surrounding cells, such as fibroblasts, are important in regulating whether the DCIS cells progress to invasive cancer,” Beebe says. “This is important because most therapy targets cancer cells, but because other cells and the microenvironment heavily influence the cancer’s growth, we are looking into developing drugs that will inhibit signals from the fibroblast.”
An Atmosphere of Collaboration
Along with many Breast Center researchers, a few years ago, Beebe’s laboratory moved to the sixth floor of the Wisconsin Institutes for Medical Research (WIMR) Tower I, which was designed with collaboration in mind. During the first quarter of 2014, many additional colleagues will move to WIMR Tower II.
“By having the right people together, we have been very successful at building teams to attack cancer in more holistic ways,” notes Beebe. “Working nearby others in this field, including those who have direct patient contact, allows us to easily share and build upon each other’s ideas.”
Another of Beebe’s Tower I floormates, Amy Fowler, MD ’07, PhD ’07, earned her dual degree through the School of Medicine and Public Health’s Medical Scientist Training Program (MSTP). Through the program, students complete the first two years of medical school followed by a doctorate degree and the last two years of medical school.
As an assistant professor in the Department of Radiology, she calls on her strong background in cellular and molecular biology. Her research aims to advance the understanding of molecular imaging for estrogen and progesterone receptors – important biomarkers that help predict cancer’s response to endocrine-based therapies.
“Our goal is to use molecular imaging to determine when endocrine therapy alone would be effective and when it should be augmented with chemotherapy and other targeted biologic therapy,” explains Fowler, who splits her time between research and patient care.
Mark E. Burkard, MD, PhD, is the associate director of the Medical Scientist Training Program and an assistant professor in the hematology/oncology division of the Department of Medicine. The Medical Scientist Training Program provides students with opportunities that span the frontiers of biomedical and health sciences.
Like Fowler, Burkard splits his time between patient care and research. He is a co-principal investigator for a research project with Wilke and Beebe. The three-year grant, funded by the Wisconsin Partnership Program, aims to develop a device to test individualized drug therapies for breast cancer patients.
“Cancer doctors have a difficult time predicting which chemotherapy will work for a given patient’s cancer. We hope our device will finally allow us to choose the right chemotherapy for an individual. I want to be able to tell my patients, ‘Yes, chemotherapy is difficult, but at least our test makes us confident that it will work for you,’” says Burkard.
‘How Mother Nature Prevents Breast Cancer’
Michael Gould, PhD, a professor of oncology, views the same health concerns as these other researchers but through a different lens. He focuses on “how Mother Nature prevents breast cancer” by studying natural variations in alleles.
Specifically, he aims to make drugs that mimic a protective allele. He notes that the quest for drugs that prevent or inhibit breast cancer has met with success and limitations.
“Tamoxifen has been shown to prevent about 50 percent of breast cancers, but the drug’s side effects are a problem for many women,” says Gould. “Now that we can detect genomes like BRCA 1 and 2, we are focusing on developing treatments to mitigate the risk in a way that patients find acceptable. For very young women, a mastectomy may not be an acceptable option.”
Gould and Wilke are collaborating with Bailey, a professor in the hematology/oncology division of the Department of Medicine, and Jenny Gumperz, PhD, associate professor in the Department of Medical Microbiology and Immunology, to explore the use of bisphosphonates, a common osteoporosis medication that may have benefits for breast cancer prevention.
“Studying the potential ability of commonly used medications like bisphosphonates to reduce the risk of developing breast cancer is one of the approaches we are undertaking in our efforts to find ways to prevent cancer,” states Bailey.
He leads one of five NCI-sponsored national groups to develop cancer prevention agents. Other approaches being tested at UW-Madison include natural products, such as nutrients and food constituents, vaccines and newly synthesized medications specific to cancer prevention.
Connecting People to Share Ideas
All of these researchers note that the Breast Center exemplifies why collaborative research is the best way to reach goals, and they credit Wilke for connecting people to share ideas.
Beebe adds, “Lee is very dedicated to helping researchers and coordinating tissue donations. She has endless energy related to helping her patients see the long-term vision of our work to foster better care through research.”
This is what Klawitter had in mind upon donating her tissue. Of the rest of her journey, she shares, “I am looking forward to a long, healthy life, one where I get to focus on being a good mom, wife and professional without the cloud of breast cancer hanging over me.”
By Kris Whitman
This article appears in the winter 2014 issue of Quarterly.