When oncology luminary Joyce A. O’Shaughnessy, MD, was in her early teens, her youngest sister, Teri, developed acute lymphocytic leukemia at age 5. Dr. O’Shaughnessy, the oldest of four girls, recalled that her sister’s struggle with the disease had a profound effect on her worldview.

“Teri went through several pediatric leukemia trials at Dana-Farber, which you can imagine was traumatic for such a young child. Moreover, it was in the early 1970s, when the field was still in its infancy,” she added. “It was a terribly difficult time, but it stirred a passion in me to pursue a career that would enable me to make progress to help vulnerable people, like Teri.”

A Career in Research Calls

Dr. O’Shaughnessy was born in Poughkeepsie, New York, and reared in the state’s capital, Albany, although both her parents were originally from Boston. When Dr. O’Shaughnessy was 13, the family returned to Massachusetts, settling in Beverly, a suburb of Boston, where she attended Beverly High School, excelling in her favorite subject: science. Dr. O’Shaughnessy, who was already thinking about medicine, went to Holy Cross College in Worcester, Massachusetts. Her sister’s 5-year battle with leukemia came to a sad end during Dr. O’Shaughnessy’s freshman year—a tragedy that led her to become a physician-scientist focusing on cancer research.

“While at Holy Cross, I was anxious to get into cancer research, so I applied for a program that allowed you to do laboratory work during your senior year. I worked for a year at the Worcester Foundation for Biomedical Research, whose claim to fame was its pivotal work on the first oral contraceptive. I studied tumor virology and wrote my senior thesis on hypotheses about virally induced leukemia. It was a rewarding experience that solidified my desire to become an oncologist,” shared Dr. O’Shaughnessy.

After graduating from Holy Cross, Dr. O’Shaughnessy pursued her medical degree at Yale University, in large part because of the school’s reputation as a research-focused institution. “While at Yale, I worked in the cancer pharmacology laboratory of Edwin Cadman, MD, who was simply a great mentor; he taught me how to focus and be productive in the lab. While there, I worked directly under another terrific mentor, Christopher Benz, MD, a physician and molecular pharmacologist who was exploring biochemically synergistic chemotherapy combinations. Chris is still active; in fact, he’s Director of the Cancer and Development Therapeutics Program at the Buck Institute for Research on Aging in Novato, California,” Dr. O’Shaughnessy noted.

Residency and NCI Fellowship

After attaining her medical degree, Dr. O’Shaughnessy returned to Boston to begin her internship and residency in internal medicine at Massachusetts General Hospital. “Although I didn’t have the opportunity to continue laboratory research, Mass General offered me a great clinical learning experience. After my residency, I started a medical oncology fellowship at the National Cancer Institute (NCI). After clinical training, I worked in the laboratory of Joe Bolen, PhD, trying to identify substrates of the oncogenic Src protein in human colon and breast cancers. I then moved to the NCI’s extramural Cancer Therapy and Evaluation Program, where I worked for 2 years, learning how cancer trials are conducted across the country and how to structure and develop clinical trial protocols,” she said.

Dr. O’Shaughnessy continued: “After that, I worked with Sam Broder, MD, PhD, who helped develop the first effective antiviral agents for HIV/AIDS. Sam was an inspirational mentor, and working with him when he was NCI Director turned out to be one of the most interesting parts of my 10 years in Bethesda. It was in the 1980s; Sam and others like Vince DeVita, Jr, MD, were frustrated that the U.S. Food and Drug Administration (FDA) wasn’t approving many cancer drugs. It was escalating into a public war, in fact. Sam asked me to coordinate an NCI-FDA Working Group that he established; we met monthly for more than 2 years, debating challenges and issues around cancer drug development and approval. We published our white paper in the Journal of Clinical Oncology in 1991, which served as a blueprint regarding cancer drug-approval endpoints¹ and led to greater NCI and FDA communication.

In 1990, Dr. O’Shaughnessy’s moved her focus into breast cancer, working with another valued mentor, Kenneth Cowan, MD, PhD, who at the time was Chief of the NCI’s intramural Breast Cancer Program. “I spent 5 years with Ken doing breast cancer patient care, teaching fellows, and developing and conducting tissue-based, translational pilot trials as a Senior Investigator, ,” noted Dr. O’Shaughnessy.

Texas Oncology Calls

Dr. O’Shaughnessy thought her NCI training as a breast cancer clinician and clinical investigator would find a perfect career fit with Texas Oncology, a large innovative practice that had developed community-based clinical trial networks in the late 1980’s. However, there were no opportunities available at the time, so Dr. O’Shaughnessy went to Louisville, Kentucky, and teamed up in practice with another NCI colleague. The plan was to set up a Texas Oncology–style clinical trials network, but resources were difficult to assemble, and things progressed at a frustratingly slow pace.

Less than a year into the project and her practice there, Dr. O’Shaughnessy received an offer from Texas Oncology; a position for a breast cancer clinician and investigator had become available, orchestrated by two superb mentors and supporters, Stephen Jones, MD, and the founding President of Texas Oncology, Merrick Reese, MD. She jumped at the opportunity and headed to Dallas to join Texas Oncology (now US Oncology), where her career as a clinician-researcher has flourished for 23 years.

Balancing Practice and Research

Dr. O’Shaughnessy is currently Celebrating Women Chair of Breast Cancer Research at Baylor University Medical Center and Chair of the Breast Cancer Program, Texas Oncology and the US Oncology Network. In these roles, she conducts investigator-initiated phase II/III trials and aids in the development and execution of pharmaceutical industry-sponsored trials within the US Oncology Network.

“In addition to the US Oncology trials, at Baylor I am conducting a series of small, translational pilot trials in metastatic triple negative breast cancer patients aimed at increasing DNA damage repair deficiency, and thus sensitivity to chemotherapy and immunotherapy. I have had a few patients who were exceptional responders in previous trials with similar approaches, so I’m trying to recapitulate their success and understand it at the molecular level, Dr. O’Shaughnessy said.

Describing her current work, Dr. O’Shaughnessy said: “I see patients 2 days a week, which are long days, and I enroll as many patients as I can into clinical trials that may improve their outcomes. The other days involve meetings, teleconferences with Baylor, Texas Oncology, and US Oncology research colleagues, translational research colleagues at TGEN and around the country, and with industry collaborators. I enjoy helping other oncologists’ patients by sharing the clincial experience I’ve gained. Seventeen years ago, together with about 25 very dedicated multidisciplinary faculty, I began serving as the coordinating director of the annual School of Breast Oncology, which is a 3-day deep-dive boot camp into all the practical aspects of breast cancer management. Over this time it’s been incredibly interesting and gratifying to see the progress that’s been made in the application of molecularly based diagnostics and therapeutics in the clinic. Poor prognosis breast cancers that were heretofore indecipherable can increasingly be understood in the context of their molecular drivers, and the explosive availability of targeted therapies makes this the most fascinating and gratifying of times.”

Renaming Burnout ‘Moral Injury’

When the conversation turned to ASCO’s work with physician burnout, Dr. O’Shaughnessy said: “The main way I decompress is being with family and friends. Nearly all of my family still live around Boston and in beautiful coastal New Hampshire, and I always look forward to trips back home.”

Dr. O’Shaughnessy mentioned that she resonates with those who “have reframed the clinician’s distress and unnecessary clericalwork as moral injury, not burnout. I agree because I feel that how I’m able to treat my patients is increasinglyin the hands of the cost-containment intermediaries of insurance companies. Oncologists suffer this moral injury not being able to offer patients the best care, due to sometimes inflexible care guidelines, even when cost is neutral or less We are in a challenging transitional period, moving steadily to science-based therapeutics, generating data that will create wholly new standards of care. Knowing that these efforts will bring major benefits and cures to patients we can’t help now keeps me energized and focused on doing the best I can each day and not dwelling on the frustrations.”

Why should a bright young student thinking about medicine chose the challenging career of oncology? “My daughter is beginning her internship in internal medicine and aspires to a career in oncology,” shared Dr. O’Shaughnessy. “Naturally, I’m proud and thrilled she’s pursuing such a meaty and meaningful field. Oncology offers two rewards that sustain practitioners for decades: deeply caring long-term relationships with patients as they battle frightening and potentially lethal disease; and the endlessly fascinating science and technologies that are completely changing how we understand and treat cancer.”

Any advice for a young oncologist? “First, develop an area of deep clinical expertise, and then find another related area of interest, such as epidemiology, clinical, translational, or laboratory science, informatics, drug development, teaching, etc., to balance the demands of the clinic and to give you tools to apply to the problems we haven’t yet solved. Oncology is such a compelling field, I can’t imagine doing anything else.” 

REFERENCE

1. O’Shaughnessy JA, et al: Commentary concerning demonstration of safety and efficacy of investigational anticancer agents in clinical trials. J Clin Oncol 9:2225-2232, 1991.