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From left: BCRF investigators Sherene Loi, MMBS (Hons), FRACP, PhD, FAHMS; Mary-Claire King, PhD; Laura J. Esserman, MD, MBA

BCRF Investigators Honored at the 2020 San Antonio Breast Cancer Symposium

Drs. Mary-Claire King, Laura Esserman, and Sherene Loi were recognized for their pioneering research
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Three BCRF investigators were honored at this year’s San Antonio Breast Cancer Symposium (SABCS), the largest conference dedicated to breast cancer in the world.

SABCS brings the breast cancer research community together to discuss new developments in the field and recognize investigators who have made an outstanding impact. This year’s awards, like the annual meeting itself, were presented virtually.

BCRF congratulates the following investigators.

Mary-Claire King, PhD

Dr. King was awarded the 2020 William L. McGuire Memorial Lecture Award for her groundbreaking research and discoveries in genetics. Dr. King, a BCRF investigator since 1997, first identified and then demonstrated a connection between mutations on the BRCA1 gene and inherited breast and ovarian cancers—a finding that expanded genetic testing as a key breast cancer prevention strategy.

In her William L. McGuire presentation, Dr. King walked through the complex and iterative process of going from identifying BRCA1 and, shortly later, BRCA2, to determining their association with certain cancers. The BRCA genes are called tumor suppressors because mutations in either gene (i.e. loss of function) make the individual highly susceptible to cancer. The paradox, as Dr. King explained, was why a mutation in a gene that is expressed in every cell and known to have vital functions in cell survival (such as DNA damage repair) would only cause cancer in specific tissues—namely hormonal tissues of the breast, ovary, and prostate, as well as the pancreas.

Her lab, in collaboration with others, would go on to resolve the paradox in the case of BRCA1, which is specifically associated with breast and ovarian cancer. In work supported in part by BCRF, they demonstrated that the specificity of BRCA1 mutation for breast and ovarian cancer was due to its role, with another protein called BARD1, in estrogen metabolism, which is highly active in the breast and ovaries. (BARD1 can also be mutated in breast cancer.) They showed that a mutation affecting the function of BRCA1 and BARD1 results in accumulation of an estrogen metabolite that is known to cause a specific type of DNA damage, which ultimately leads to cancer. Interestingly, repair of the DNA damage requires BRCA1, so BRCA1 mutation has a dual effect in cancer—both increasing DNA damage and reducing the cell’s ability to repair it.

Dr. King’s story came full circle in highlighting the success of a new class of drugs called PARP inhibitors that specifically target cells with dysfunctional DNA repair caused by BRCA1 or BRCA2 gene mutations. Currently, two PARP inhibitors, olaparib (Lynparza®) and talzoparib (Talzenna®) are FDA approved for treatment of breast and ovarian cancers caused by BRCA1 of BRCA2 mutations. “It took 20 years from the discovery of BRCA1 and BRCA2 to the development of this therapy, which has dramatically reduced cancer progression or death in ovarian cancer patients,” Dr. King said.

Laura J. Esserman, MD, MBA

Dr. Esserman received the Brinker Award for Scientific Distinction in Clinical Research, which recognizes advances in the clinical management of breast cancer. Dr. Esserman, a BCRF investigator since 1998, was selected as this year’s recipient based on her seminal contributions in clinical research, which are paving the way toward more personalized approaches to breast cancer care. Since 2002, Dr. Esserman has spearheaded the groundbreaking BCRF-supported I-SPY trials based on an innovative clinical trial model designed to rapidly determine the most effective treatments for each patient, thereby accelerating drug approval and enabling new therapies and prevention strategies to reach patients faster.

In her Brinker award presentation, Dr. Esserman described the next of phase of I-SPY. I-SPY 2.2 builds on advances from I-SPY 1 and I-SPY 2 to improve the pace and success of personalized treatments in a precision-based approach that treats the patient based on her tumor biology and adapts therapy to tumor response. Dr. Esserman closed by explaining how the I-SPY approach is now being used to test treatments for COVID-19.

Sherene Loi, MMBS (Hons), FRACP, PhD, FAHMS

Dr. Loi was honored with the American Association for Cancer Research (AACR) Outstanding Investigator Award for Breast Cancer Research, which is underwritten by BCRF. This award recognizes an investigator under the age of 50 whose work in basic, translational, clinical, or epidemiological research has advanced, or has the potential to advance, our understanding of breast cancer and has, or is likely to have, a significant impact on detection, diagnosis, treatment, or prevention of the disease.

AACR recognized Dr. Loi, a BCRF investigator since 2015, for her contributions in immunotherapy for breast cancer patients. In her award presentation, she explained how our understanding of the tumor-immune microenvironment has evolved, particularly in regard to an immune cell type called tumor-infiltrating lymphocytes (TIL), which have been predictive of treatment response to immunotherapy and chemotherapies in breast cancer. Unfortunately, most breast cancers have very few TILs and Dr. Loi’s current effort, involving collaborations around the world, is aimed at devising ways to increase TIL content in breast tumors by furthering our understanding of the biology of the tumor-immune landscape.

Read more of BCRF's SABCS 2020 coverage here.

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