A Journey of a Lifetime: Noted Breast Cancer Researcher in Far-Flung Pursuit of a "Cure"

Beth Fand Incollingo @fandincollingo | February 12, 2013
Dr. Brian Leyland-Jones
Brian Leyland-Jones, MB BS, PhD
Brian Leyland-Jones is committed to eradicating cancer—and he’s willing to go anywhere to do it.

During a career spanning more than 30 years, that philosophy hasn’t been easy on the doctor’s personal life. But it has given the renowned oncologist and translational scientist the opportunity to conduct groundbreaking laboratory and clinical research, and to treat patients, at a half-dozen of the world’s top cancer institutions— not to mention becoming a citizen of two countries besides his native England.

In April 2012, Leyland-Jones, MB BS, PhD, made his latest move into the directorship of Edith Sanford Breast Cancer Research in Sioux Falls, South Dakota, a new genomic research program and treatment center. In that role, he is overseeing the use of a $100 million gift from Denny Sanford, a credit and banking industry entrepreneur whose mother died of breast cancer when he was 4 years old. The center will explore the application of genomics in matching targeted treatments to patients.

At the same time, Leyland-Jones is serving as a senior scientist at the related Sanford Research, an integrated health system headquartered in Sioux Falls and in Fargo, North Dakota. In his lab there, the doctor uses model systems to discover pathways that drive cancer and find therapies that suppress them.

Although accepting the position at Edith Sanford meant leaving a tenured professorship at Emory University, in balmy Atlanta, Georgia, to move to snowy South Dakota, the 63-year-old doctor didn’t hesitate.

“When the CEO of Edith Sanford asked me how I’d feel about living here, I said that I would go anywhere I felt the mission could be achieved,” he recalled. “I want to leave this world in a better state than how I found it, and this is the greatest opportunity I have of making a significant difference. I truly feel that breast cancer is going to transform, in the next four to seven years, into an extremely chronic disease, and that we will come as close to the word ‘cure’ as we possibly can. It’s an absolutely transformative time.”

Changing the Course of Treatment

An expert in pharmacodynamics, pharmacokinetics, and pharmacogenetics, Leyland- Jones has contributed to that change by designing and running an array of clinical trials, most of them in patients with breast cancer. Along the way, he helped develop the anthracycline, antimetabolite, and platin families of drugs that are now mainstays of oncologic treatment, as well as the targeted therapies trastuzumab and bevacizumab.

Leyland-Jones has also helped to disprove some theories about how best to treat breast cancer patients. He was a major contributor to the design of the phase III HERA trial (ESMO 2012: Abstract LBA6), which demonstrated that two years of adjuvant trastuzumab was no better than the standard one year of treatment for women with HER2-positive, early-stage breast cancer.

In the ATAC (Lancet. 2010;11[12]:1135- 1141) and BIG 1-98 (J Natl Cancer Inst. 2012;104[6]:441-451) trials, Leyland-Jones and colleagues cast doubt on the use of the cytochrome CYP2D6 as a biomarker for the benefits of tamoxifen in patients with hormone receptor-positive breast cancer.

“When I first joined the cancer world, something like 70% of the treatments we administered to patients did not benefit them,” Leyland-Jones said. “Over the years, there have been a number of markers postulated to guide therapies much better; two of these were serum HER2 testing and CYP2D6. In doing larger trials and overviews, we’re showing that some of these postulates don’t work, and trying to come up with really genuine biomarkers to direct which patients should get which drugs.”

The doctor also left his mark on the cancer community by running the Developmental Chemotherapy Section of the National Cancer Institute (NCI), in Bethesda, Maryland, which at the time was testing between 70 and 80 potential anticancer drugs in settings from the laboratory to phase III clinical trials. In addition, he built oncology programs into comprehensive cancer centers at McGill University in Montreal, Canada, where he served as the Minda de Gunzburg Chair in Oncology, and at Emory University, where he was executive director of the Winship Cancer Institute.

As Leyland-Jones moved through those experiences, he became increasingly convinced that he needed to focus his attention on exploring genomics in cancer treatment.

At Sanford, he’ll start that quest with a small trial that will select treatment for patients with metastatic breast cancer based on an analysis of the full genomic sequence of their tumors. Ideally, future trials at Sanford will add to the evidence that genomically guided medicine is superior for treating breast cancer patients compared with nongenomically guided medicine, the doctor said.

“I’d not be here at Sanford, preparing with our partners to run full genomic trials over the next two, three, or four years, if I did not think the proudest accomplishments are yet to come,” he said.

Taking the Lead at Edith Sanford

As excited as Leyland-Jones is about the project, it represents only part of what he does as director of Edith Sanford Breast Cancer Research.

Since he began there, the doctor has divided his working hours about equally between tumor boards or clinically related activities, time in his own lab—whose staff moved with him from Emory—and other national or international biomarker research efforts in large cooperative groups, including the Eastern Cooperative Oncology Group (ECOG), the International Breast Cancer Study Group (IBCSG), and Breast International Group (BIG). Having recently secured his South Dakota license, he has also started seeing breast cancer patients twice a week.

In addition, the doctor teaches residents and fellows. “If there’s one simple message that I always try to get across to them,” he said, “it’s that every decision that is made about any patient outcome is a completely shared experience. You have to respect what the patient wants to do.”

At the same time, oncologists must guide their patients, he said.

An example of what can happen when the culture of an area has a strong effect on patient attitudes, Leyland-Jones said, is the high rate of mastectomy among patients with breast cancer in South Dakota, as compared with that in other states.

“Patients in this area of the country often come in and say, ‘I’ve got this cancer, and I don’t care—I’ll have a mastectomy,’ ” he said. “But there are so much kinder and more precise methods, like lumpectomy or radiation, so the continued education of our patients is really important. It allows you and the patient to make the absolute best decision together.”

Another of Leyland-Jones’ goals at Sanford is helping to shape it as a model of sophisticated cancer-care delivery to a rural community.

Sanford’s network reaches into such areas, in part, by sending out mammography vans, the doctor said. In all, the network provides nearly 65,700 mammography screenings each year.

Including 35 hospitals, 36 long-term care facilities, and 140 clinic locations, Sanford has more than 1200 physicians who care for patients in 126 communities within eight states, and also conducts national and international collaborations through the Sanford World Clinic, according to a spokesman.

“Our health network covers more, in terms of land mass, than any other,” Leyland-Jones said.

Sanford also boasts a growing patient biobank, the doctor added. “The idea is that, as we accumulate more and more knowledge on genomic medicine, one can go to the biobank and use DNA, RNA, and protein aberration patterns to individualize both risk assessment, and also what interventions are needed in patients,” he said. “We’re making this a key part of the total health experience.”

Brian Leyland-Jones, MB BS, PhD . . .

Dr. Brian Leyland-Jones
  • Is 63 years old.
  • Enjoyed the book Who Says Elephants Can’t Dance? Inside IBM’s Historic Turnaround, by Louis V. Gerstner, Jr. “It’s about leadership, transformation, and how to implement a visionary direction to a large organization,” he said.
  • Cites The Bridge on the River Kwai as one of his favorite movies. “Most importantly,” he said, “it teaches that, if we are too set in our ways and blinded by a particular goal, we can miss the obvious.”
  • Especially as it applies to cancer research, appreciates a quote from Albert Szent Györgyi: “Discovery consists in seeing what everyone else has seen and thinking what no one else has thought.”
  • Held his most boring job ever—counting nuts and bolts for an engineering company—when he was 11 or 12 years old.
  • Enjoys scuba diving and playing tennis.
  • At one time considered becoming a concert pianist, and still plays the instrument.
  • Because he held long-term medical posts in several countries, is a citizen of the United States and Canada, as well as his native England. “I’ve always said that my heart belongs to the US, but my soul to England,” he said.
  • Over the years, has held leadership positions in many large medical organizations, including the Eastern Cooperative Oncology Group; the Cancer and Leukemia Group B; the International Breast Cancer Study Group; the National Cancer Institute of Canada; and BIG-North American Breast Cancer Groups.
  • Within the last decade, has been honored with the Vivian Saykaly Visiting Professor Award by the Cedars Cancer Institute in Montreal; named an Eminent Scholar by the Georgia Research Alliance and a Distinguished Cancer Scholar by the Georgia Cancer Coalition; and, as director, achieved NCI Cancer Center designation for Emory University for the first time in 30 years.
  • Is a member of the executive steering committee of a Tissue Bank Consortium in Asia run by the National Foundation for Cancer Research. The bank contains tissues collected during clinical trials during the last 30 years, potentially offering information about cancer’s drivers, therapies, and outcomes. “We met with the Chinese minister of health last year in New York,” Leyland-Jones said, “and are beginning to reach an understanding about transfer of materials from their outstanding tumor banks to analyze in our own facilities, with sharing of all information between the countries. It’s part of a larger picture of collaboration and partnership-building in research.”

Determined to Make a Difference

Leyland-Jones didn’t start out aspiring to be a doctor or a scientist.


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