On the Frontier of Breast Cancer Research With Joyce A. O’Shaughnessy, MD

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My sister’s death [from acute lymphocytic leukemia] at age 10 made me passionate about cancer research.
— Joyce A. O’Shaughnessy, MD

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Nationally regarded breast cancer researcher and clinician Joyce A. O’Shaughnessy, MD, was born in upstate New York, just outside of Albany, where she attended grade school before her family moved to Beverly, Massachusetts, a suburban town 26 miles from Boston, where her family’s roots were. Throughout her early school years, she was a lover of science, spending countless hours concocting experiments on her home chemistry set. Although medicine was high on her list of potential careers, it was a family tragedy that planted the seed for her career in oncologic research.

A Family Tragedy

The eldest of four girls, Dr. O’Shaughnessy recalled the life-altering event. “When I was 14 years old, my younger sister, Teri, who was 5 at the time, developed acute lymphocytic leukemia. She was treated at Dana-Farber on a series of pediatric leukemia clinical trials, even as far back as 1970. Teri died when she was 10, and I was a 19-year-old freshman at Holy Cross College in Worcester, Massachusetts. It was a difficult time. My sister’s death made me passionate about cancer research,” said Dr. O’Shaughnessy.

However, for a 19-year-old woman in the early 1970s, doing cancer research was an uncommon goal, but Dr. O’Shaughnessy was undeterred. “I made an appointment with the dean and told him that I needed to begin doing cancer research and asked whether I could do it here at Holy Cross or did I need to transfer to a large university. The dean actually provided my research funding. I was studying tumor virology and wrote a senior thesis on leukemia,” she shared.

Road to Research

Following her graduation from Holy Cross, Dr. O’Shaughnessy entered Yale University to pursue a medical degree. “I chose Yale in part because the school focused heavily on research, even requiring med students to spend time on a project in the lab. It was an influential experience in my career, as I had the opportunity to work in the lab of Edwin Cadman, MD, and he was a superb mentor to me and many other students over the years,” she noted.

The biggest leap forward, in my opinion, has been the explosion of incredibly precise diagnostic technologies, at the tissue, blood, and host levels.
— Joyce A. O’Shaughnessy, MD

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Dr. O’Shaughnessy also had the opportunity to work with another noted researcher who became her mentor, Christopher Benz, MD, who led translational research focused on identifying molecular strategies to improve breast cancer diagnostics and therapeutics. Dr. Benz is currently Director of the Cancer and Developmental Therapeutics Program at the Buck Institute for Research on Aging in Novato, California.

“During medical school, my research centered on what was the exact metabolic effects of the chemotherapies we were delivering, and back then there weren’t that many agents. My earlier research at Yale solidified my decision to pursue a career in oncology,” said Dr. O’Shaughnessy.

National Cancer Institute

After attaining her medical degree from Yale School of Medicine, Dr. O’Shaughnessy began her internship and residency in internal medicine at Massachusetts General Hospital in Boston in 1985. “Mass General was a great clinical experience, but I didn’t have the opportunity to pursue my research interests. So, after my residency, I began my medical oncology fellowship at the National Cancer Institute (NCI) in 1987. I stayed at the NCI for 10 years, and during that time, I became a senior investigator, working with Mr. Joseph Boland, who was also a mentor who greatly influenced my research career,” said Dr. O’Shaughnessy. She added, “At that time, I was studying the oncogene c-Src.”

Dr. O’Shaughnessy’s interest moved from the lab into clinical research. After learning the clinical trials process, she worked with Samuel Broder, MD, PhD, who was a co-developer of some of the first effective drugs for AIDS. “It was one of the most interesting times of my career. I coordinated a 2-year-long effort between the Oncology Division of the U.S. Food and Drug Administration (FDA) and the NCI to develop consensus on new drug approval endpoints,” she explained. “It’s important to note that this was in the early 1980s, and there were basically no drugs approved for cancer. So, you can imagine there was a lot of consternation within the growing oncology community. Vincent DeVita, MD, who hired me, was Director of the NCI at the time, and he was quite vocal, justifiably so, about the need to get cancer drugs approved and out to our patients.”

Dr. Joyce A. O’Shaughnessy: Some Career Highlights

  • Helped bring capecitabine and gemcitabine to the market
  • Developed the School of Breast Oncology
  • Examined clinical trial concepts and protocols during her 2 years at the NCI’s Cancer Therapy Evaluation Program (CTEP)
  • Delineated new cancer drug approval endpoints with NCI and CTEP while Special Assistant to the NCI Director
  • Helped establish the NCI–U.S. Food and Drug Administration Fellowship Training Program
  • Chaired the American Association for Cancer Research Task Force on Treatment of Intraepithelial Neoplasia, which published clinical trial strategies to accelerate development of new agents for this lesion

Dr. O’Shaughnessy continued: “I was first author on a Journal of Clinical Oncology paper that still stands today as an interesting roadmap to new drug approval endpoints. In 1990, I transitioned to the NCI’s Clinical Breast Cancer Division, and that was when my focus on breast cancer was cemented. My mentor at that pivotal time was Kenneth Cowan, MD, PhD, who was Head of NCI’s Clinical Breast Cancer Division. I stayed at the NCI until 1995, and it was an incredibly enriching experience.”

Texas Oncology: Patient Care and Research

In 1997, Dr. O’Shaughnessy relocated to Dallas, Texas, where she joined Texas Oncology and worked within a large statewide medical oncology practice. “I’ve been at Texas Oncology for about 21 years, and about 50% of my time is spent in the clinic, taking care of women with breast cancer. I am also Chair of the U.S. Oncology Clinical Breast Cancer Trials committee. At Baylor University Medical Center, I am Chair of Breast Cancer Research and the Celebrating Women Chair in Breast Cancer at Baylor’s Charles A. Sammons Cancer Center. That’s where I conduct small, translational pilot trials of about 10 to 20 enrollees in a setting where we can test novel hypotheses. So, I’m very busy doing what I love. I have the best of both worlds in that I care for patients with cancer and also have ample time reserved to pursue my interests in the research lab.”

Diagnostics Will Lead the Way

Asked for a closing thought about the state and future of oncology, Dr. O’Shaughnessy said, “I began treating women with breast cancer 32 years ago in 1985, and we were terribly frustrated with a lack of therapeutic options. We now have a large array of therapeutic tools for our patients, but for the most part we have seen only modest benefits. That said, there have been exceptions such as trastuzumab (Herceptin) and a few other agents. However, the biggest leap forward, in my opinion, has been the explosion of incredibly precise diagnostic technologies, at the tissue, blood, and host levels. To move treatments ahead, you need to know everything about the diseases you’re treating. And on that front, we’re seeing great promise.”

DISCLOSURE: Dr. O’Shaughnessy has consulted for Arno Therapeutics, AstraZeneca, Celgene, Corcept Therapeutics, Eisai, Genentech, GSK, Lilly, J&J, Merrimack, Novartis, Pfizer, Roche, Sanofi, Takeda, and Medfusion.