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ARRA Investments in Breast Cancer

Public Health Burden
Breast cancer is the most common form of cancer in women in the United States, other than non-melanoma skin cancer. In 2009, it is estimated that more than 190,000 new cases of breast cancer will be diagnosed among American women, and it will cause more than 40,000 deaths. Breast cancer is the leading cause of cancer death among Hispanic women. Among white, black, Asian/Pacific Islander, and American Indian/Alaska Native women, it is the second most common cause of cancer death.

Medical imaging techniques (methods of producing pictures of parts of the body) have become essential elements in the early detection and diagnosis of breast cancer. However, the most widely used breast imaging technique, mammography, misses approximately 20 percent of breast cancers (false-negative results) and the frequency of false-positive results (suggesting cancer is present when it is not) is 5 to 10 percent. It is extremely important, therefore, to find ways to improve the performance of mammography and to develop alternative imaging techniques. ARRA funding is enabling researchers to pursue both of these avenues:
  • Researchers are developing an automated reasoning system that uses features found on mammographic images and patient demographic risk factors to classify abnormalities as benign or malignant. The goal is to assist and enhance radiologist interpretation of mammograms.1
  • Three imaging techniques—a three-dimensional version of mammography (digital tomosynthesis mammography or DTM), automated ultrasound scanning (AUS), and a new optical imaging technique called spectroscopic photoacoustic tomography (S-PAT)—will be combined to see if this multimodal approach can reduce false-negative and false-positive breast imaging results.2
Although many effective therapies for breast cancer have been developed, existing treatments can cause serious or debilitating side effects and some breast tumors can be refractory or become resistant to them. Therefore, additional, less-toxic therapies are urgently needed. The ACTNOW (Accelerating Clinical Trials of Novel Oncologic Pathways) program is designed to address this need and holds great promise in shortening the time it takes to move new cancer treatments from discovery, to development, to approval and safe use by cancer patients. ARRA funding is supporting 37 ACTNOW clinical trials, including:
  • A phase I/II trial in which invasive breast cancer is treated before surgery with two new drugs that target different signaling pathways cancer cells use to proliferate and survive.3
  • A phase II trial in which invasive breast cancer is treated before surgery with chemotherapy plus or minus bevacizumab, a monoclonal antibody that inhibits the development of new blood vessels to tumors.4
  • A clinical trial of an anticancer vaccine plus an immune system stimulant in the treatment of metastatic breast cancer.5
Genomic Research
Cancer is essentially a genetic disease. Therefore, identifying the important genomic changes that occur in cancer development and progression will advance our understanding of the disease at the molecular level and improve our ability to diagnose, treat, and prevent it. The Cancer Genome Atlas (TCGA) project was designed with this goal in mind. ARRA funding is allowing the scope of TCGA to be expanded to include more than the original three cancer types and is supporting other cancer-related genomic research:
  • Breast cancer is one of two new cancer types included in TCGA. With ARRA funding the list of cancer types will grow to more than 20.  
  • The Vanderbilt Institute of Chemical Biology (VICB) and the Vanderbilt Ingram Cancer Center (VICC) are collaborating to form the Vanderbilt Molecular Target Discovery and Development Center (VMTDDC), with the aim of exploiting the wealth of existing and future cancer genomic data to develop new treatment modalities for cancer.6
Health Disparities Research
Among U.S. women, black women are more likely to die from breast cancer than women from other racial and ethnic groups. Lack of medical coverage, barriers to early detection and screening, unequal access to improvements in cancer treatment, and differences in tumor biology may contribute to this difference in survival. Nevertheless, as long as such disparities exist, our work to eliminate the suffering and death due to cancer is far from complete. ARRA funding is supporting research to understand and address the causes of cancer health disparities. For example:
  • The Howard University Cancer Center and Johns Hopkins University Cancer Center are extending their partnership to conduct research on cancer screening, diagnosis, prevention, treatment, and supportive care, with a special focus on cancer in African-Americans.7
Comparative Effectiveness Research
There is little evidence from research to support the effectiveness and/or optimal delivery of many healthcare practices used in the United States. The result, therefore, is uneven and sometimes poor-quality care from region to region, as well as unnecessarily high associated financial costs. ARRA funding is helping to address this issue by supporting comparative effectiveness research. For example:
  • The Breast Cancer Surveillance Consortium (BCSC) is conducting research on breast cancer screening intervals (1 versus 2 years), screening modalities (X-ray film mammography, digital mammography, and magnetic resonance imaging), and patient risk factors to determine their influence on breast cancer detection, mortality, and associated costs.8

  1. 3R01CA127379-03S1 -- Machine learning for improved mammography -- Burnside, Elizabeth S. (WI)
  2. 3R01CA091713-07S1 -- Combined digital X-ray, optical, and ultrasound breast imaging -- Carson, Paul L. (MI)
  3. 3U10CA062487-16S1-- A phase I/II dose-escalation and exploratory neoadjuvant study of an oral gamma-secretase inhibitor (GSI) plus hedgehog inhibitor GDC-449 (NSC #747691) administered in patients with breast cancer -- LoRusso, Patricia M. (MI)
  4. 3U01CA031946-28S1 -- Randomized phase II 2x2 factorial trial of the addition of carboplatin +/- bevacizumab to neoadjuvant weekly paclitaxel followed by dose-dense AC in hormone receptor-poor/HER-negative resectable breast cancer -- Schilsky, Richard L. (IL) (Cancer and Leukemia Group B)
  5. N01CM62208 -- Combination immunotherapy utilizing the p53/adenoviral dendritic cell vaccine plus the indeolamine 2,3 dioxygenase inhibitor 1-methyl-D-tryptophan in p53 mutated metastatic breast cancer -- Sullivan, Daniel M. (FL)
  6. 1RC2CA148375-01 -- The Vanderbilt Molecular Target Discovery and Development Center -- Marnett, Lawrence J. (TN)
  7. 3U54CA091431-09S1 -- The Howard University Cancer Center/Johns Hopkins Cancer Center Partnership -- Smoot, Duane T. (Washington, D.C.)
  8. 1RC2CA148577-01 -- Comparative effectiveness of breast imaging strategies in community practice -- Miglioretti, Diana L. (WA) (Group Health Cooperative)

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