Advancing the fight against breast cancer

Identifying genetic subtypes Developing a mammoglobin vaccine Improving mammography screening

Over the past two decades, the range of treatments for breast cancer has improved dramatically and so have the survival statistics. Today, more than 80 percent of patients can look forward to long-term freedom from disease. But that still leaves a group of patients with a persistently poor prognosis who need more therapy than the rest. How can outcomes be improved for these women?

In his research and clinical work, medical oncologist Matthew Ellis, MB, BChir, PhD, approaches breast cancer patients like Martha Christmas with an overarching goal: To provide personalized therapy that improves outcomes and preserves quality of life.
In his research and clinical work, medical oncologist Matthew Ellis, MB, BChir, PhD, approaches breast cancer patients like Martha Christmas with an overarching goal: To provide personalized therapy that improves outcomes and preserves quality of life.

“The answer is to unravel the genetic complexity of breast cancer,” says Matthew Ellis, MB, BChir, PhD, a physician-researcher at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “What we need is a cancer genome atlas to document every single genetic anomaly that occurs in breast cancer so we can delve into the consequences of those changes.”

Ellis, Anheuser-Busch Distinguished Professor in Medical Oncology, is leading a five-year, $8.5 million effort funded by the National Cancer Institute’s Specialized Program for the Evaluation of Cancer Signatures (SPECS) to identify the various subtypes of breast cancer, each with its own molecular characteristics and sensitivity to certain drugs. Working with collaborators from the University of Utah and the University of North Carolina, Ellis hopes to develop an easily administered gene profiling test that can be used in patients with early stage disease.

“If we are successful, this test will provide critical information on patients’ outcomes, particularly identifying those whose outcome is likely to be poor,” Ellis says. “Then we can focus our clinical trials on them and spare women who don’t need more drugs from the side effects of additional therapy.”

This research will dramatically expand the understanding of breast cancer, currently seen as at least four distinct diseases based on past genetic findings. For example, scientists know that the gene HER2 is amplified in about 20 percent of all breast cancers, and drug companies have developed therapies that fight this overexpression and destroy cancer cells bearing the abnormality.

“This subpopulation of breast cancer, HER2-positive disease, was considered to be a poor prognosis subtype, and now it has been transformed into one of the better prognosis subtypes,” Ellis says.

To define other such subgroups, Ellis and his colleagues have gained access to thousands of formalin-preserved breast cancer samples banked over the past decade and more. They are targeting 100 genes in the tumor samples, analyzing their activity and classifying each patient’s disease. Because they know what treatment patients received and what the outcomes were, they also can determine which therapies worked best for each cancer subtype.

This work requires sophisticated analytical tools – including gene expression profiling – and the expertise of research partners like Washington University’s Genome Sequencing Center and new recruit D. Craig Allred, MD, a molecular pathologist. It is supported in part by funding from the Susan G. Komen for the Cure organization and the Fashion Footwear Association of New York.

With help like this, the future of breast cancer diagnosis and treatment will look very different. Ten years from now, Ellis says, clinicians will be using a whole new vocabulary to describe breast cancer subtypes, and newly identified patients will undergo much more extensive work-ups to determine what kind of cancer they have and which therapy is best.

“This individualized, tailored approach to breast cancer will lead to all sorts of marvelous things: improved quality of life, saving women from drugs they do not need, and focusing resources and clinical investigation on patients who need it,” Ellis adds. “And all that will ultimately realize our goal, which is a cure for everyone.”

Breast Cancer Vaccine

Another promising new frontier in breast cancer research at Siteman is the pursuit of a vaccine to shrink or prevent recurrence of the disease. Collaborators on this project include William Gillanders, MD, associate professor of surgery; Thallachallour Mohanakumar, PhD, Jacqueline G. and William E. Maritz Professor of Immunology and Oncology; Timothy Eberlein, MD, Siteman director; Timothy Fleming, PhD, research associate professor of surgery; and Simon Goedegebuure, PhD, assistant professor of surgery. The group is working to develop a DNA vaccine for mammaglobin A, a protein first isolated at Washington University by Fleming and Mark Watson, MD, PhD, associate professor of pathology. While the protein is expressed at low levels in normal breast tissue, it is dramatically overexpressed in some 80 percent of breast cancers.

In earlier research funded by Komen for the Cure, Mohanakumar demonstrated in a mouse model that this DNA vaccine can generate a potent anti-tumor response. Now, with funding from the Cancer Treatment Research Foundation and the U.S. Department of Defense, the team is planning a phase I clinical trial of the mammaglobin vaccine in human patients.

“This is the first time anyone has tried to vaccinate against mammaglobin,” Gillanders says. “If it works, it could ultimately be used with existing patients to prevent a recurrence or even with high-risk patients to prevent the development of cancer.”

New Mammography Van

Joanne Knight Breast Health Center manager Susan Kraenzle says Siteman's new mammography van provides a convenient and potentially lifesaving service by offering breast cancer screening in community settings to women who may not otherwise have access to t
Joanne Knight Breast Health Center manager Susan Kraenzle says Siteman’s new mammography van provides a convenient and potentially lifesaving service by offering breast cancer screening in community settings to women who may not otherwise have access to these services.

Detecting breast cancer as early as possible to increase the chance of survival is a priority for Siteman’s Joanne Knight Breast Health Center and mobile mammography program, which recently purchased a replacement van. Both programs now are outfitted with new digital mammography equipment, making Siteman an all-digital mammography center. The Avon Foundation provided funds to purchase digital equipment for the new van. The vehicle itself was acquired using funds raised by A&E Group, led by CEO Barry Horn, and Celebrate Fitness, an annual exercise event chaired by volunteers Missy Fish and Kris Hansford.

The decision to move into digital imaging came in fall 2005, after the results of the landmark Digital Mammographic Imaging Screening Trial (DMIST) became public. The trial enrolled nearly 50,000 women, more than 3,300 of them at Siteman under the leadership of radiologist Dione Farria, MD, MPH. The results showed that digital mammography can detect breast cancer better in certain cases: in women under 50, in premenopausal and perimenopausal women, and in women with dense breasts.

In addition to digital equipment, the mammography van has a new look, says Susan Kraenzle, Breast Health Center manager. In keeping with the theme “Every Woman, Everywhere,” the sides of the van are decorated with an array of women designed by St. Louis artist Laura Bailey. The van travels as far as Missouri’s Bootheel to screen women, including underserved women who receive free mammograms through a variety of special programs.


Patient “celebrates” her survival

Through their Celebrate Fitness workout event, Missy Fish, left, and Kris Hansford have helped raise thousands of dollars for the Siteman Cancer Center.
Through their Celebrate Fitness workout event, Missy Fish, left, and Kris Hansford have helped raise thousands of dollars for the Siteman Cancer Center.

In March 2006, nearly 1,000 people gathered at Washington University for Celebrate Fitness, a workout event that would improve their health and benefit area women at the same time. Some did strength training or kickboxing, while others tried yoga or water aerobics. More than 100 hardy souls attended a “boot camp” led by a no-nonsense drill instructor.

“It was a killer, but our boot camp participants loved it,” says Missy Fish. She and Kris Hansford are the co-chairs of Celebrate Fitness, which marked its ninth anniversary by raising more than $250,000 for the Siteman Cancer Center through registrations, donations and corporate sponsorships. Proceeds from the 2005 and 2006 events helped purchase a replacement van for Siteman’s mobile mammography program. The new van began screening area women for breast cancer in October.

Fish knows the pain of breast cancer herself, as well as the importance of early detection. In 1991, when she was only 39 years old, she was volunteering at a health fair, urging women to get mammograms, when she decided to schedule one, too. There was no history of breast cancer in her family nor did she have any symptoms.

But that sudden inspiration may have saved her life. On her mammogram, Siteman physicians discovered intraductal breast cancer, caught so early she did not even need chemotherapy or radiation therapy after surgery. In 2005, the same kind of cancer appeared in her other breast, but again, doctors found it early because they were closely monitoring her.

Now Fish is more committed than ever to raising money for cancer care and research at Siteman. This year, she and Hansford again organized Celebrate Fitness. And in November 2006, she helped chair a new event, CUREiosity, a loft party featuring music and a live fashion shoot that raised more than $40,000 for Siteman.

“A lot of people in St. Louis don’t know how important the Siteman Cancer Center is,” Fish says. “It is such an impressive institution, and we are fortunate to have it in our backyard.”