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Pathways to Discovery: Summer 2013

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UChicago Discoveries Paved the Way for Modern Breast Cancer Treatment

A series of scientific findings made at the University of Chicago in the 1950s through 1980s transformed the way breast cancer is treated. The initial discovery of the estrogen receptor, made by a chemist named Elwood V. Jensen, PhD, in 1958, led to a test that is still used today to determine the best therapy for patients with breast cancer.

In the 1950s, removal of a patient’s ovaries worked for the treatment of some breast cancers, but little was known about the role of the hormone estradiol (also known as estrogen) in tumor growth. Dr. Jensen, then assistant professor of surgery, had been closely collaborating with Charles Huggins, MD, who received the Nobel Prize for Physiology and Medicine for his fundamental work in hormonal therapy for prostate cancer. Dr. Jensen decided to focus his work on identifying the role of estradiol in the growth and development of breast cancer. He devised a method to tag estradiol with a radioactive compound, enabling him to follow the events that occurred when the hormone interacted with tissues in rats. Estradiol appeared to bind specifically to a protein in cells of the reproductive tract.

Dr. Jensen discovered that this protein, called the estrogen receptor, is activated by estrogen and shifts to the cell’s nucleus. Once in the nucleus, the estrogen receptor binds to DNA and changes the expression profile of various genes and proteins that promote tumor growth. Until Dr. Jensen’s discovery, hormones were thought to act via metabolic pathways. “His discovery profoundly changed the thinking of the field,” said Geoffrey Greene, PhD, Virginia and D. K. Ludwig Professor, chair of the Ben May Department for Cancer Research, and associate director for basic sciences at the University of Chicago Medicine Comprehensive Cancer Center.

Next, Dr. Jensen developed a test to detect estrogen receptors in breast cancer cells. As a result, Dr. Jensen and his colleagues discovered that about two-thirds of breast cancers express the estrogen receptor, of which half depend on estrogen for growth. Although the test was effective, it was complicated and laborious, Dr. Greene said. Other researchers in the field soon recognized the importance of the test and began devising simpler methods.

Dr. Greene joined the laboratory in 1974, and together with Dr. Jensen and colleagues, used an emerging technology to develop monoclonal antibodies directed against the estrogen receptor. The technology enabled them to quickly and accurately detect and count estrogen receptors in breast and other tumors. By 1980, this test was incorporated into the standard of care for patients with breast cancer.

“Now, every breast cancer in the Western world and in many other parts of the world is routinely analyzed for the expression of the estrogen receptor,” said Dr. Greene. By determining which tumors have estrogen receptors, doctors can identify who will be responsive to anti-estrogen therapy and who should begin chemotherapy or radiation.

Dr. Jensen is considered the father of the field of nuclear hormone receptors, which play an integral role in the development and progression of hormone-responsive cancers, including breast and prostate cancers. He received the prestigious Albert Lasker Award for Basic Medical Research in 2004 and died in December 2012 at the age of 92.

“Out of all the tumor biomarkers that are around today, the estrogen receptor still stands out as one that is used routinely–– even after more than 30 years,” said Dr. Greene. “It has withstood the test of time, and it is still considered valuable as a therapeutic and prognostic marker.”   

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