Good news at Fred Hutch

Celebrating our achievements
Joseph Unger, Gary Lyman, Andrew Hsieh
Recent notable accomplishments: Dr. Joseph Unger (left) was the lead statistician in finding new hope for preserving fertility during breast cancer chemotherapy; Fred Hutch health economist Dr. Gary Lyman edits essential reference book for clinical oncologists; Dr. Andrew Hsieh discovers new type of biomarker showing promise in predicting prostate cancer recurrence Photos by Bo Jungmayer / Fred Hutch News Service

We want to recognize the excellent work and achievements of our staff and faculty and will be regularly highlighting them in this space. Here are some recent notable accomplishments:

New hope for preserving fertility during breast cancer chemotherapy

Dr. Joseph Unger, a biostatistician in Public Health Sciences, was the lead statistician on an international clinical trial, published March 4 in The New England Journal of Medicine, which found a hormone-blocking drug given during chemotherapy prevents premature menopause and ovarian failure and helps preserve fertility in breast cancer patients.

“Anywhere from one third to two thirds of premenopausal women receiving standard chemotherapy agents experience premature menopause,” said Unger, who led the data analysis on behalf of SWOG (formerly known as the Southwest Oncology Group), whose statistical center is based at Fred Hutchinson Cancer Research Center.

Until now, the only proven way to preserve fertility was to harvest a woman’s eggs prior to the beginning of chemotherapy treatment, Unger said.

The Prevention of Early Menopause Study, or POEMS, led by researchers at Cleveland Clinic, found that a woman’s chance of coming through chemotherapy with her fertility intact is greatly improved if she is given a medication called goserelin, a synthetic version of a naturally occurring gonadotropin-releasing hormone. The drug works by temporarily putting the ovaries in a “resting” state and preventing their normal cycle, which makes them less vulnerable to the toxic effects of chemotherapy.

The study involved 218 premenopausal women worldwide diagnosed with early stage, hormone-receptor-negative breast cancer who were randomized to receive standard chemotherapy with or without goserelin every month for the duration of treatment.

Those who received goserelin experienced an 8 percent ovarian failure rate compared to a 22 percent failure rate in the control group two years after treatment. In addition, 21 percent of women in goserelin arm became pregnant within the first five years post-treatment compared to only 11 percent in the control group during the same time frame.

The study also found that goserelin might actually make chemo work better – an unexpected benefit.

“Although the study was not powered to examine cancer outcomes differences, we explored cancer outcomes to ensure there were no detrimental effects from the goserelin treatment,” Unger said. “To our surprise we found that women receiving goserelin with their chemotherapy had both better disease-free and overall survival than women receiving chemotherapy alone.”

Fred Hutch health economist Dr. Gary Lyman edits essential reference book for clinical oncologists

Oncologist and health economist Dr. Gary Lyman, co-director of the Hutchinson Institute for Cancer Outcomes Research at Fred Hutchinson Cancer Research Center, is editor of the second edition of the Oxford American Handbook of Oncology released Feb. 25 from Oxford University Press, a nonprofit run by Oxford University.

The textbook is considered an essential reference for medical students, residents, and clinical oncologists seeking a current resource on state-of-the-art cancer care. The reference is designed to help guide clinical decision-making, from treatment choices to best-practice guidelines.

“This represents an updated and expanded edition of the handbook, which continues in the popular bulleted style that the Oxford handbooks have made popular across a range of medical disciplines,” said Lyman, a member of the Public Health Sciences Division at Fred Hutch. The book is available in both hard-copy and digital formats.

The 864-page textbook covers cancer biology, genetics, prevention and screening, treatment complications, and supportive care. The handbook also provides background on molecular cancer biology, etiology, and epidemiology.

More than 50 oncology professionals from Duke University and other institutions contributed to the reference guide. Lyman, a professor of medicine at the University of Washington, also served as editor of the first edition, which was published in 2009 while he was on the faculty at Duke.

New type of biomarker shows promise in predicting prostate cancer recurrence

Many men experience prostate cancer as a curable disease. But in those whose disease recurs and metastasizes, or spreads to distant organs, death is inevitable. Pinpointing patients at high risk of relapse is imperative to giving them early treatment options when they are more likely to be effective.

Dr. Andrew Hsieh, a researcher in the Fred Hutch Human Biology Division, has identified two biomarkers that may improve oncologists’ ability to predict which patients’ prostate cancer will recur after surgery, long before the development of visible cancer elsewhere in the body. According to Hsieh, “once clinically verified, biomarkers like these have the potential to help clinicians identify patients who are more likely to relapse and therefore may benefit from additional therapy after surgery.”

In a paper published March 3 in Oncotarget, Hsieh’s team showed that the levels of two proteins are closely linked to prostate cancer outcomes. In collaboration with groups at the University of California, San Francisco, and the University of California, Los Angeles, Hsieh found that patients with higher levels of proteins called YB-1 and MTA1 were much more likely to suffer prostate cancer recurrence and three times as likely to require treatment such as hormone-blocking drugs or radiation therapy.

Moreover, adding YB-1 and MTA1 levels to clinical factors currently used to predict prostate cancer recurrence improved their predictive potential.

The search for prognostic biomarkers has primarily focused on changes in DNA and messenger RNA, the intermediate molecule that enables the genetic message encoded in DNA to be translated into proteins. But Hsieh suspects that a whole field of potential biomarkers remains little studied: proteins whose levels are altered in the absence of gene mutations or changes in messenger RNA expression. In pursuing this hypothesis as a physician-scientist, Hsieh is navigating uncharted waters.

Proteins are cells’ “work horses,” Hsieh explained. They underpin how cells live, behave and die. But the process of producing proteins from RNA messenger molecules is not static, he said. “It’s not like a factory that does the same thing every time. There are levels of regulation.” Changes in how key proteins are produced, independent of alterations to the proteins’ genes or messenger RNA, have been shown to drive cancer. YB-1 and MTA1 are just two of potentially hundreds of such proteins, and they would never have been discovered if Hsieh had not ventured beyond traditional DNA and RNA biomarker discovery techniques.

Hsieh previously identified YB-1 and MTA1 as potential protein biomarkers in a groundbreaking study conducted at UCSF with Dr. Davide Ruggero, using new technology that measures changes in protein production that occur independently of any changes in messenger RNA. “This work is the clinical application of that finding,” he said.

Hsieh aims to uncover how differences in the levels of specific proteins — without accompanying DNA or RNA changes — can give clues to how cancers develop and potentially recur. Such mechanisms that control these phenomena could also be the target of drugs, currently in development, which block the key steps in which RNA messages are translated into proteins.

The findings not only have the potential to improve care for prostate cancer patients but strengthen the hypothesis that the control of protein abundance produces a potentially rich source of biomarkers for many types of cancer. “We have the opportunity to revisit the topic of biomarker discovery in a completely new way,” Hsieh said. “It’s great to be working at the forefront of basic research and clinical medicine here at the Hutch.”

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