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UC's Breast Health Network Expanding Cancer Risk Assessment Protocol, Research

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Athena Breast Health Network, a collaboration involving five University of California medical centers, is expanding the scope of its program to standardize breast cancer risk assessment, which allows doctors to determine which patients should receive additional interventions such as genetic counseling or follow-up testing.

The network this week announced it would implement its risk assessment protocol for breast cancer patients who are part of the Edith Sanford Breast Cancer Initiative launched by Sanford Health system. Athena and Edith Sanford will conduct a pilot study that will investigate SNPs implicated in breast cancer risk.

Ultimately, the institutions in the Athena network – mostly California-based entities, including UC Davis, UC Irvine, UC Los Angeles, UC San Diego, UC San Francisco, and other private and public members – aim to recruit 4,000 women to participate in a large trial seeking to characterize the genomic underpinnings of breast cancer.

"The University of California Breast Health Network is interested in expanding its vision for patient-tailored prevention and treatment by combining care and research. Athena is designed to learn from every patient that enters the system and can adapt based on new findings," Laura van 't Veer, UCSF principal investigator of the Athena Breast Health Network, told PGx Reporter over e-mail this week.

Toward this goal, Athena has developed a screening questionnaire that patients complete at home before coming into the clinic. The survey asks patients about their personal history with breast and ovarian cancer, family history of diseases, medical information, genetic predisposition, lifestyle, demographics, and other medical information. Those patients that healthcare providers deem high-risk are referred to specialists or genetic counselors, or are enrolled in risk reduction programs.

Currently this questionnaire, as well as BRCA1/2 testing for hereditary breast and ovarian cancer risk, is part of the standard of care for patients in Athena's network. "The health questionnaire asks every patient to answer questions on known genetic/family risk; however, not all patients are aware that genetic predisposition [testing] and counseling could be of benefit to them," van 't Veer said.

Across Athena's five university medical centers, more than 45,000 women have been enrolled in the network. Of these, doctors referred 15 percent of women to breast health specialists, a portion of which had a family history of breast cancer and a smaller subset had known BRCA1 or BRCA2 mutations.

"Testing for larger panels is currently considered by the genetic counselors at the medical centers, but is not yet a standard," van 't Veer added. The network plans to eventually integrate breast density information and SNP testing into its risk assessment framework.

Before providing SNP testing across the network, however, Athena will use the Illumina OncoChip platform to conduct a pilot study involving 3,000 women to better characterize the SNPs associated with breast cancer risk. Van 't Veer cited a study led by Douglas Easton of the University of Cambridge and published in Nature Genetics last year that identified SNPs at 41 new breast cancer susceptibility loci with genome-wide significance. The authors concluded there were more than 1,000 additional loci involved in breast cancer susceptibility.

Most of these SNPs confer a low or intermediate risk on carriers, unlike BRCA1/2 mutations, van 't Veer noted. "The pilot study will allow us to investigate the impact on risk distribution and consequences for tailoring prevention (i.e. frequency of mammographic screening," she said. "This step needs to be completed first, before the larger implementation."

When Athena integrates breast density and SNP testing with its standard risk models, including family history and hormonal risk factors, researchers hope to be able to better pinpoint the appropriate age when doctors should start screening patients for breast cancer and how frequently, she explained. The network hopes to roll out this integrated risk-based screening protocol in the third quarter of 2014.

Athena will conduct this 3,000-patient pilot study with the Edith Sanford Breast Cancer Initiative, its first partner outside of California, before attempting a larger genomic study in 4,000 patients. The larger trial is still in the planning stages.

Van 't Veer noted that Edith Sanford and Athena became partners because the groups share a common vision to improve breast cancer prevention and treatment. In 2011, Sanford Health — the largest rural non-profit healthcare system serving 126 communities through 39 hospitals in nine states — launched the Edith Sanford Breast Cancer Initiative to boost the state of the science around breast cancer by spurring genomic research and funding.

In partnership with the University of South Dakota, Sanford Health also operates a research facility in Sioux Falls. Through its collaboration with Edith Sanford, Athena has the opportunity to expand its research efforts to a large community-based setting, van 't Veer noted. "As a movement this has the potential to grow even larger," she added.

In the next few months, Sanford Health will start implementing the Athena screening and risk assessment model in pilot locations. Last year, healthcare providers within Sanford Health saw 660 new breast cancer patients across its 39 hospitals, and this year they expect to see a similar number of patients.

One of the main hindrances to conducting research around breast cancer risk, however, is the dearth of patient samples, particularly tumor tissue. Athena has collected 7,900 biospecimens from women in California, which researchers will use for the pilot and other studies.

Currently, women who come to Edith Sanford for breast cancer screening have the option of submitting a blood sample that will be stored in a biobank and used for research. To date, Edith Sanford researchers have collected blood samples from more than 2,000 patients and healthy subjects, 329 of which are breast cancer patients.

Some ongoing research projects at Edith Sanford are collecting tumor tissue from cancer patients as well. By implementing Athena's risk assessment protocols, David Pearce, chief operating officer and VP for Sanford Research, is hoping that more women will see the importance of research in this area and donate tissue and blood samples for research.

"This study will be able to give us a much more far-reaching understanding of the other mutations that might potentially be contributing to the development of breast cancer," Pearce told PGx Reporter. "The best treatment for breast cancer is prevention."

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