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Executive Summary

During 2009, the California Breast Cancer Research Program (CBCRP) funded 53 new single- and multiple year research projects that will advance scientific knowledge about breast cancer. With these new awards, we are investing almost $16 million at 22 California institutions. This annual report summarizes the studies that were completed during 2009 and lists the newly funded and ongoing studies.

Table 1. Research Projects Funded in 2009 by Subject Area

	Number		Percentage of
	of Research projects	Amount	Total Funding
Community Impact of Breast Cancer	11	$2,068,006	13.0%
Etiology and Prevention	8	$8,581,176	53.8%
Detection, Prognosis and Treatment	15	$2,222,312	13.9%
Biology of the Breast Cell	19	$3,072,094	19.3%
Totals	53	$15,943,588	100%

Designed to push breast cancer research in new, creative directions, the CBCRP is funded primarily by a California state tax on tobacco. Breast cancer activists have played a leading role in the CBCRP from the beginning. They helped write and pass the statewide legislation that created the Program in 1993. Since then, the CBCRP has provided over $205 million for research in California to prevent, treat, and cure breast cancer.

Women with breast cancer and survivors of the disease are involved in all levels of the CBCRP’s decision making, including decisions about which projects get funded. With input from these advocates, the CBCRP has established a record for funding cutting-edge studies and jump-starting new areas of research. The Program’s goal is to fund the projects that will lead most rapidly to the end of the breast cancer epidemic.

The need is urgent. Every two hours, on average, a California woman dies of breast cancer. More than 272,000 Californians are living with the disease, and over 22,000 more will be diagnosed this year. Over the past three decades, some progress has been made. The rate at which California women got breast cancer climbed steeply from 1973-1988 and stayed near the 1988 rate for more than a decade. Since then, the breast cancer incidence rate has dropped by eight percent. Between 1988 and 2005, the breast cancer death rate in California dropped by 29 percent.

In November 2009, the US Preventive Services Task Force (USPSTF) announced new recommended guidelines for screening for women with normal risk of developing breast cancer. They advised that: women in their 40s of average risk for breast cancer should not get routine mammograms; women who are between 50 and 74 should get mammograms every other year. The panel based their recommendations on their analysis of the efficacy of mammography in reducing breast cancer mortality balanced by the harms of over treatment (including scarring, radiation and drug side effects) and psychological distress due to false positives. The resulting analysis led the committee to conclude that as a general screening tool, the harms outweighed the benefits of mammography for screening pre-menopausal women.

The recommendations highlight how critical it is to develop better screening and prevention strategies for breast cancer. This debate arises because we are dealing with an imperfect technology that forces us to make tough choices. The true challenge to the CBCRP and researchers is to make the debate irrelevant by finding an accurate, non-toxic way to identify life threatening breast disease, prevent it, and cure it.

This report has been prepared by the University of California pursuant to Article 1 of Chapter 2 of Part 1 of Division 103 of the California Health and Safety Code, Section 104145; and the Revenue and Taxation Code Sections 30461-30462.1 and 18791-18796 amended by AB-28 Oct. 11, 2008. The following required reporting elements will be addressed in this report:

The number and dollar amounts of research grants, including the amount allocated to indirect costs. The CBCRP awarded almost $16 million for 53 single- and multiple-year research projects, funded in the form of 60 grants to 22 California institutions in 2009. A complete list of newly funded grants can be found in Table 2.
The institutions and campuses receiving grant awards. All funded grants are listed with the recipient institutions in Table 2 and in the Research Progress and Results section of this report.
The subject of research projects. All of the investigator-initiated projects funded by the CBCRP involve key questions in one or more of the following research areas:

Basic Biology of the Breast (normal breast biology and breast cancer pathogenesis)
Breast Cancer Causes and Prevention
Earlier Detection, Diagnosis, and Treatment of Breast Cancer
Community Impact of Breast Cancer (sociocultural behavioral studies and health policy)

The CBCRP is also devoting 30 percent of program funding to its Special Research Initiatives, which is a program-initiated endeavor to investigate two of the most challenging and under-researched areas in breast cancer: the role of the environment in breast cancer and the reasons why some groups of women—based on characteristics such as ethnicity or race—bear a greater burden of the disease.

The relationship between federal and state funding for breast cancer research. The CBCRP takes several steps to avoid duplication of funding at the individual research project level and in the Program’s research priorities. We identify and attempt to fill important gaps in knowledge about breast cancer. We review priorities yearly in light of changes in the research field, successes and failures of previous funding initiatives, and the results of previous funding. Additionally, as founding members of the International Cancer Research Portfolio and participating members of the Collaborative Summit on Breast Cancer Research, we are able to ensure that CBCRP funding complements, rather than duplicates, grants bestowed by other funding organizations.

The CBCRP’s Breast Cancer Research Council sets the Program’s funding priorities, taking into account:

Opinions from national breast cancer experts
Opinions from California advocates and activists, healthcare providers, public health practitioners, community leaders, biotechnology scientists, and academic researchers
Current literature on breast cancer and current gaps in knowledge
Comparisons with portfolios and programmatic goals of other funding agencies
In-house evaluations of the efficacy of CBCRP grant mechanisms and topic areas in fulfilling program goals

The relationship between each project and the overall strategy of the research program. The following ten goals are used to set overall programmatic research priorities and calls for applications.

California Specific: Fund research that utilizes resources particular to California and/or addresses a breast cancer need that is specific, but not necessarily unique, to the burden of breast cancer in California.
Career Development: Fund research that helps recruit, retain, and develop high-quality California-based investigators who engage in breast cancer research.
Collaboration: Fund research that uses multidisciplinary approaches and helps foster collaboration among California scientists, clinicians, advocates, community members, patients, survivors, and others.
Disparities: Fund research that addresses disparities, inequalities and/or underserved populations in California.
Innovation: Fund innovative research (i.e., new drugs, new strategies, new paradigms, new applications of tested strategies in new populations and contexts).
Non-duplicative: Fund research that complements, builds on, and/or feeds into, but does not duplicate, other research programs.
Outcome Driven: Fund research that will improve public health outcomes (e.g. preventing breast cancer, detecting breast cancer, effective treatments, and quality of life).
Policy: Fund research and evaluation that will have policy implications for breast cancer in California.
Responsive: Fund research that is responsive to the perceived breast cancer research needs, opportunities, and expectations of the CBCRP as identified by scientists and the public in California.
Translation: Fund research that is on a critical path for practical application and leads to more effective products, technologies, interventions, or policies and their application/ delivery to Californians.

The review of each individual grant application is also designed to ensure that the research projects funded by the CBCRP have both high scientific merit and programmatic interest. Each individual application is evaluated by external scientific review committees for specific aspects of scientific merit including, but not limited to, impact on breast cancer, innovation, feasibility, and approach. All applications of sufficient scientific merit undergo a programmatic review by our Breast Cancer Research Council for responsiveness to program priorities, including whether it fits the goals of the award type, integrates advocacy issues, and is an under-funded research question.

A summary of research findings including discussion of promising new areas. Summaries of all of the research projects completed in 2009 are included in the body of this report. Listed below are just a few of the findings:

Irene Yen, Ph.D., at the University of California, San Francisco, studied the association between neighborhood environment and obesity in pre-adolescent girls. She identified the types of city planning policies and neighborhood conditions (food store availability, fast food chains, parks, traffic conditions) that can improve girls’ diet and physical activity, influence their pubertal changes, and, potentially, decrease their breast cancer risk as adults. See page 34.
Joan Bloom, Ph.D., at the University of California, Berkeley, and colleagues investigated the quality of life of young breast cancer survivors 10 years after their initial diagnosis to determine how long problems persist. They found that young breast cancer survivors are aging prematurely with respect to certain treatment related problems. However, in general, at this point in their lives, their quality of life was comparable to that of women without cancer. See page 35.
Resistance of breast cancer stem cells to treatments may be responsible for a cancer recurrence or metastases. Frank Pajonk, M.D., Ph.D., at the University of California, Los Angeles, and colleagues explored how breast cancer stem cells respond to radiation treatments. In addition to verifying that these cells were less likely to be susceptible to radiation, Dr. Pajonk and his team discovered a new breast cancer stem cell marker that can be used to identify, track, and more effectively target breast cancer stems cells. See page 42.
Michael Press, M.D., Ph.D., at the University of Southern California, in Los Angeles, investigated whether it is possible to predict whether a HER2-positive tumor will respond to anthracycline therapy based on the presence of extra copies of the TOP2A gene. His findings could lead to better targeted anthracycline therapy. See page 43.
Steven Artandi, M.D., Ph.D., at Stanford University, in Palo Alto, and colleagues extended their work probing the role of telomerase, an enzyme that protects chromosomes during cell division, in relation to breast cancer stem cells. They found that telomerase is a cofactor in the Wnt pathway, an important circuit in cancer and stem cell division. The findings from this research could lead to the development of new and potentially less toxic breast cancer treatments based on telomerase inhibitors. See page 49.
Florence Shaffner, Ph.D., at the Scripps Research Institute, in La Jolla, showed that blocking the activity of targeting tissue factor (TF), a molecule involved in blood clotting and wound healing, reduced spontaneous tumor development and growth in mice. This suggests that TF signaling plays an important role in breast cancer by regulating how a tumor develops blood vessels and gains the ability to metastasize. See page 49.

Inclusion of women and minorities in research studies. The CBCRP issued 60 grants to pursue 53 research projects in 2009. Forty-three percent (23 of 53) of the research projects that the CBCRP funded in 2009 studied either women or tissues from women. The remaining 57% were laboratory studies that did not directly involve women or human tissues.

Of the 23 research projects that involved women or tissues from women, 91% (21) had women as participants in the study.

Out of the (21) studies that included women:

Ninety percent (19) include minority women in the study.
Thirty-three percent (7) are focused on minority women.
Thirty-eight percent (8) are focused on underserved women.

The CBCRP’s activities, goals, and progress during 2009 are described in this report, along with the challenges that must be confronted in order to decrease the economic burden and human suffering caused by breast cancer in California.