Recovery Act Funding Helps Breast Cancer Researchers Continue to Innovate
Funding from the American Recovery and Reinvestment Act has allowed NCI to continue supporting many promising projects in diverse areas of breast cancer research, ranging from prevention to treatment. Below are three examples of the innovative work currently underway using Recovery Act funding.
Downsizing Surgery for Breast Cancer
Modern breast cancer researchers are concerned not only with improving treatment and survival for the disease, but also avoiding the use of aggressive surgery or chemotherapy when less-intensive treatment would provide equal benefit to a patient.
Traditionally, during surgery for breast cancer, doctors performed a procedure called axillary lymph node dissection (ALND): the removal of most of the lymph nodes near the armpit, to check for the regional spread of cancer. Doctors then used this information about whether or not cancer had spread to the lymph nodes to decide if a patient required chemotherapy. ALND has many potential side effects, including pain and numbness in the arm and hand, lymphedema (the build of up lymphatic fluid in the arm), and a reduced ability to fight infections.
“Roughly two-thirds of women who were having this procedure done didn’t have any cancer identified in their lymph nodes, so it was really an unnecessary procedure for them as far as we could tell,” said David Krag, M.D., SD Ireland professor of surgical oncology at the University of Vermont College of Medicine.
Recovery Act funding recently helped Dr. Krag and his colleagues finish a practice-changing clinical trial of less invasive lymph-node surgery. His team wanted to know if using a radiotracer to locate and remove only the sentinel lymph nodes—the first few lymph nodes that tumor cells would have spread to—would be as effective as ALND for guiding further treatment but have fewer side effects.
In that trial, called the National Surgical Adjuvant Breast and Bowel (NSABP-B32) trial, women without cancer cells found in their sentinel nodes were randomly assigned to no further lymph-node surgery or to ALND. The researchers enrolled more than 5,000 women, but ran into funding difficulty near the end of the trial. Because early-stage breast cancer had a very good prognosis overall, patients in a trial like NSABP-B32 must be followed for a long time before potential differences in outcomes can be seen between the groups.
The researchers could not publish their results without this long follow-up, which required continued funding, but the review committee managing their grant was hesitant to renew their funding without published proof-of-progress: a perfect Catch-22. In 2009, Dr. Krag received a Recovery Act grant to finish the trial and publish the results.
“The Recovery Act funding was absolutely critical to finishing the trial—we were just on the verge of closure,” said Dr. Krag. The results, published at the end of 2010, showed that the less invasive sentinel-node biopsy “is not just equivalent, but better” than ALND for women without cancer found in their sentinel nodes, because “it helps achieve the same cure, but with considerably fewer side effects.”
Using Gene Expression to Predict Response to Treatment
A difficulty in choosing the best adjuvant treatment for a patient with breast cancer “is the heterogeneity of disease, both in clinical outcomes and genomic architecture, which make predictive medicine difficult in breast cancer,” said Dr. Matthew Ellis, M.B., B. Chir., Ph.D, professor of medicine at the Washington University School of Medicine.
For several years, researchers have recognized five major subtypes of breast cancer, defined by their gene expression profiles: luminal A, luminal B, normal breast-like, HER2-positive, and basal-like. These five types have different prognoses and vary in response to treatment. For example, only HER2-positive breast cancer responds to treatment with the targeted drug trastuzumab (Herceptin).
With the help of a Recovery Act grant, Dr. Ellis and his group have developed and begun to commercialize a new test based on nanotechnology, which can rapidly and successfully identify the five genetic subtypes, even in archived, paraffin-embedded samples from past clinical trials.
His team used their Recovery Act funds to validate the new test and partner with a company called Nanostring Technologies, who will shepherd the test through FDA approval and bring it to market, hopefully by 2013 or 2014, and with the Cancer and Leukemia Group B (CALGB), a cancer cooperative research group. “Universities and the CALGB aren’t commercial entities—we have to partner with our colleagues in industry to deliver these types of tests to our patients, and the Recovery Act funding allowed us to do that,” said Dr. Ellis. “If the test receives FDA approval, it would secure the future of a startup biotech company, which would employ a lot of people.”
“I’m a firm believer in the personalized oncology agenda, in avoiding overtreatment of patients with chemotherapies that may be ineffective or unnecessary, and bringing new treatments to patients with poor prognosis that are not helped by currently approved agents,” said Dr. Ellis. “I think the Recovery Act should be something that the public should be excited about, because this kind of research looks at clever ways to more cost-effectively deliver healthcare; to produce better outcomes with fewer side effects because we really understand more about the disease, and can therefore design more effective and safer treatments.”
Understanding the Complete Environment to Tailor Prevention Strategies
Dr. Scarlett Lin Gomez, Ph.D., a research scientist at the Cancer Prevention Institute of California, is looking at how the characteristics of individual neighborhoods, including walkability, traffic, crime, access to recreational facilities, and access to healthy food, might interact with socioeconomic status and individual risk factors for breast cancer to contribute to known disparities across and within different racial and ethnic groups, both in the incidence of the disease and in survival.
“I think that cancer disparities are affected by the complex interplay of many factors, ranging from an individual’s biology all the way to the neighborhoods in which we live, which in turn can affect what our behaviors are,” said Dr. Gomez.
Recovery Act funding was vital for getting her project off the ground, allowing the Cancer Prevention Institute of California to recruit two new research scientists, as well as maintain the support of existing staff. “This much needed boost came at a time when I see a lot of talented scientists with really bright ideas give up or think of giving up their careers because it’s just so much more difficult to get grant support. Without the Recovery Act, I don’t know if we would have been able to do our study,” said Dr. Gomez.
The data used in Dr. Gomez’s project were collected by two studies conducted in the San Francisco Bay area, the Northern California site of the Breast Cancer Family Registry and the San Francisco Bay Area Breast Cancer Study, which together comprise a diverse group of women: more than 75 percent are African American, Latino, or Asian. Information on individual risk factors for breast cancer was collected by direct interviews of almost 8,000 women, about half of whom had been diagnosed with breast cancer.
“We hope that by considering these interactions among individual and neighborhood factors we can do a better job of pinpointing the specific populations that might require more interventions, or interventions better tailored toward specific groups,” said Dr. Gomez. “We hope to share our findings and get the thoughts of groups and individuals who can work with us on translating our results into meaningful prevention and intervention strategies.”