UPMC researchers solving treatment resistance in most common breast cancer

February 07, 2018

PITTSBURGH, Feb. 7, 2018 - At Magee-Womens Research Institute (MWRI) and UPMC Hillman Cancer Center, a large team of clinical and laboratory researchers dedicated to understanding treatment resistance in the most common form of breast cancer have identified a new genetic change in the estrogen receptor (ER) that contributes to therapy resistance. ER-positive breast cancer, diagnosed in two-thirds of breast cancer patients, is fueled by the presence of estrogen in the body. Anti-estrogen therapy is usually successful in treating the disease initially, but ER-positive breast cancers will often recur because tumors develop a resistance to treatment.

Published in the Annals of Oncology, the research identifies the presence of ER gene (ESR1) fusion proteins in treatment-resistant breast cancer. This is the first time that recurrent ESR1 fusion proteins have been identified in human breast cancer, and understanding how they function could lead to improved treatments for the disease.

"We first identified this change in a patient who had ER-positive breast cancer, received anti-estrogen therapy, had her breast cancer recur and eventually passed away from the disease," said senior author Adrian Lee, Ph.D., director of the Women's Cancer Research Center at MWRI and UPMC Hillman Cancer Center, and professor of Pharmacology & Chemical Biology at the University of Pittsburgh. "A member of our lab noticed the mutation while performing posthumous genetic analysis from tissue in our organ donation program, and over time we were able to identify many more cases of this mutation in patients with recurrent disease." This work was performed in collaboration with Foundation Medicine Inc., a genomic testing company that examined ESR1 fusions in close to 10,000 breast cancers sequenced with the FoundationOne CDx test.

According to Lee, ESR1 fusion proteins "outsmart" traditional treatment by splitting in half and eliminating the binding site that anti-estrogen therapy targets.

"Physicians will continue administering anti-estrogen therapy, not realizing this genetic mutation has occurred," said Lee. "Now that we understand the change, though, we can detect it with a blood test and help improve treatments for this form of the disease."

According to Lee, genetic analysis will soon be the dominant field of ER-positive breast cancer research, eventually leading to improved treatments and patient outcomes.

"Genomic sequencing is telling us so much about breast cancer. I believe the research we are doing in the laboratory will have a significant clinical impact in the near future, and the work we are doing will play a large part in improving patient care and survival," said Lee.
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Lead authors on this research are Ryan J. Hartmaier, Ph.D., of Pitt, MWRI and Foundation Medicine Inc., and Sally E. Trabucco, Ph.D., of Foundation Medicine Inc.

This research was funded by U.S. Department of Defense Congressionally Directed Medical Research Programs fellowship W81XWH-11-1-0582, Fashion Footwear of New York and the Breast Cancer Research Foundation. This project used services and equipment supported by National Institutes of Health (NIH) awards P30CA047904, UL1-RR024153 and UL1-TR000005. Additional support is from Scientific Advisory Council award SAC150021 from Susan G. Komen for the Cure and the Hillman Foundation, as well as NIH training grant 2T32GM008424-21 and fellowship 5F30CA203095.

About Magee-Womens Research Institute

Magee-Womens Research Institute (MWRI) is the largest research institute in the US devoted exclusively to health conditions affecting women and infants. The Institute is leading discoveries and advancing knowledge in the field of reproductive biology and medicine, translating this knowledge into improved health, wellness and disease prevention for women, engaging our community in women's health, and training the present and future generations of women's health researchers.

About UPMC Hillman Cancer Center

UPMC Hillman Cancer Center, the region's only National Cancer Institute-designated Comprehensive Cancer Center, is one of the largest integrated community cancer networks in the United States. Backed by the collective strength of UPMC and the University of Pittsburgh School of Medicine, UPMC Hillman Cancer Center has more than 60 locations throughout Pennsylvania, Ohio, Maryland and New York, with seven international cancer centers and partnerships. Consistently ranked by U.S. News & World Report for excellence in cancer care, the more than 2,000 physicians, researchers and staff are leaders in molecular and cellular cancer biology, cancer immunology, cancer virology, biobehavioral oncology, and cancer epidemiology, prevention, and therapeutics. UPMC Hillman Cancer Center is transforming cancer research, care, and prevention -- one patient at a time.

http://www.upmc.com/media

Contact:

Cyndy Patton
Office: 412-586-9772
Mobile: 412-415-6085
PattonC4@upmc.edu

Amy Charley
Office: 412-586-9778
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CharleyA@upmc.edu

University of Pittsburgh Schools of the Health Sciences

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