Searching for Possibilities, Hortobagyi Found Greatness

Gabriel N. Hortobagyi, MD

As a boy growing up in 1940s Budapest, Hungary, Gabriel N. Hortobagyi, MD, devoured as many books as he could— receiving them as gifts and tearing into biographies about physicians and scientists, and learning about how science changed the world. He was prompted by his mother, who had wanted to become a doctor herself but never did since “it was not socially appropriate for women to go into the profession in the 1910s, 1920s, and 1930s.” Her influence was strong, though. “By the time I was in middle school, I knew I would go into the sciences and be a physician,” he said. “I never looked back.”

But social unrest in Hungary created some roadblocks. In 1949, the secret police (backed by the Soviet Union, which had invaded Hungary) forced families like Hortobagyi’s into concentration camps in southeast Hungary. He was 3 years old at the time. They lived there until 1953, when the Soviet leader, Joseph Stalin, died.

“We were given amnesty that year, on the condition that we could never return to Budapest,” said Hortobagyi. “My parents could not get a job in any supervisory positions, and neither my sisters nor I were allowed to finish our education. Had I stayed in Hungary, I would have been a driver or a street sweeper.”

Instead, his family moved to Vienna, Austria, where Hortobagyi, at age 10, didn’t know enough German to attend school, so he remained in a refugee camp. By 1957, his family had emigrated to Bogota, Colombia, where he was able to resume his schooling. He then attended the Universidad Nacional de Colombia, a public medical school in Bogota that offers admission to 120 students out of more than 6000 applicants. His family’s foresight in moving where they might find opportunity serves as just one example of a thread that’s been woven throughout Hortobagyi’s life and career as one of the world’s foremost breast cancer researchers and clinicians: to go where it’s possible to make great things happen.

Curious About Cancer

Hortobagyi’s own journey took him to The University of Texas MD Anderson Cancer Center, where is a professor of Medicine and the Nellie B. Connally Chair in Breast Cancer, and to a stint as president of the American Society of Clinical Oncology. His research accomplishments include the development of presurgical chemotherapy regimens as well as anthracyclines and taxanes. He also helped advance the initial development of gene expression profiling in breast cancer. The irony of his journey is not lost on Hortobagyi. “I was able to surpass what could have been a completely different path in life to help countless breast cancer patients, train hundreds of clinicians in the field, and create lifesaving drug regimens that have helped transform the field of oncology from a hopeless one to one bursting with potential and lifesaving treatments,” he said.After finishing medical school in Colombia, Hortobagyi accepted an internal medicine clinical residency at St. Luke’s Hospital, Case Western Reserve University in Cleveland, Ohio. Why the move from Colombia to Cleveland? The program paid its residents a third more than any other residency program Hortobagyi had considered. The city also boasted a large Hungarian population at the time, giving him “a certain sense of comfort,” he said.

The Case Western residency was the launching pad for Hortobagyi’s earliest interest in oncology. In the 1960s and early 1970s, “there was no such thing as oncology, and I had not given a single thought to cancer,” he said. When physicians went on rounds, patients with cancer “were mostly looked at as ‘here are the people on death row; it’s just a question of time before they die and there is nothing we can do about them.’ If there were patients with cancer on rounds, we would skip to the rooms to someone curable. You didn’t want to tell someone, ‘You’re just going to die of your disease.’ If you’re not trained for that, it’s very difficult.”

But in 1972, his second residency year, Hortobagyi received a flyer about a cancer conference at the Ohio State University in Columbus, Ohio; intrigued, he went. “It was a life changer,” said Hortobagyi. After the “boring talks about how lung and colon cancer kills everybody,” Emil J. Freireich, MD, DSc, a University of Texas MD Anderson Cancer Center researcher and fellow 2015 Giants of Cancer Care recipient, “gave this electrical dynamic speech. He said, ‘We are curing acute leukemia of childhood, and Hodgkin’s, and we are well on our way to fighting cancer. We are going to lick this disease.’” Hortobagyi was transformed.

“This presentation woke me up and knocked the socks off my feet,” he said. “I realized this was the next frontier.” Upon returning to Cleveland, he wrote a letter to Freireich, asking if there were any openings in MD Anderson’s training programs. There were—and Freireich instructed Hortobagyi to come down south. It seemed to be an unusual move, and one he wasn’t entirely prepared for, in at least one sense: “I packed all my belongings in my trunk—I had a ’71 Dodge Challenger that didn’t have air conditioning,” he said. “I was going to die in Texas without air conditioning.” And his colleagues wondered about his motivation, too.

“My training companions in Cleveland asked, ‘Why on earth are you going to Texas? You can’t shoot. You don’t speak proper English.’ I didn’t know, but I cannot tell you the sense of excitement I had—that we are going to take care of this and we are going to cure cancer.”

Before he left Cleveland, though, he oversaw some direct care for two patients with widespread metastatic breast cancer that had also spread extensively to the bone. “There was no way to support them, and they didn’t have good pain medications— it was horrible,” Hortobagyi recalled.

Furthering the Cancer Fight

Then he remembered reading an abstract from a few years before that discussed a cocktail of five chemotherapy drugs that offered a 90% remission rate. “I was very excited for that, but my boss said, ‘Don’t get excited; leave them alone.’ But I wrote a chemotherapy prescription for them, and the assistants shrugged, and gave the patients the chemotherapy. I was almost expelled from my program for it, for being ‘in contempt of court.’ But my saving grace was that both women responded to the treatment and walked out of the hospital. That pretty much sealed my passion for treating breast cancer.”Once at MD Anderson Cancer Center, Hortobagyi took in all he could about breast cancer and knew he had found his passion. “It’s a fascinating disease,” he said. “Some people will die in 6 months and others [will] live the rest of their lives. Some respond to hormones and there’s an endocrine part of it. There were a lot of issues in the development of oncology, with cytotoxic agents and immunotherapy. It brought together a number of disciplines. I never really gave a second thought to brain tumors or cancers of the left big toe. It was so obvious that I was fascinated by breast cancer.”

He moved up through the academic ranks, from instructor to professor and eventually, became the director of the entire breast cancer research program. Throughout that time, he helped pioneer various drug treatments for breast and other cancers. They included giving patients chemotherapy before surgery to remove tumors, rather than afterward; chemotherapy before surgery has since become the standard of care for many different types of cancer. He also helped develop the practice of adding bisphosphonates to treatment regimens to address bone metastases. And he also introduced numerous cancer drugs, including tamoxifen, Taxol, Taxotere, cisplatin, and a number of other hormones now used regularly for cancer treatment.

But he noted that such accomplishments are based on what others have done before him. “It’s hard to think of science in terms of ‘you invented something,’” he said. “We all build on the observations and accomplishments of our predecessors. It’s just that we had the opportunity and ability to synthesize the knowledge that existed at the time.”

His colleagues, however, are more likely to sing his praises. “To my point of view, he is one of the greatest oncologists in the world and THE best specialists in breast cancer,” said David Khayat, MD, PhD, the head of the Medical Oncology Department at Pitié-Salpêtrière Hospital and an oncology professor at Pierre and Marie Curie University, both in Paris, France. “His contribution to this field is tremendous: from primary chemo (neoadjuvant) to the role of platinum in breast cancer. He contributed to the development of a huge number of new drugs in this indication, including the taxanes, vinorelbin, anthracyclines, bevacizumab, pertuzumab.”

Sharing Knowledge

Such accomplishments are a testament to Hortobagyi’s life philosophy of perseverance: If at first you don’t succeed, try, try again. “One of the most important things for progress and for success is to fail,” he said. “If you have not failed, you haven’t tried. And if you haven’t failed, you are not thinking outside the box. Failure is an important part of life and progress and makes life exciting.”Hortobagyi’s days are packed with intention and activity. After arriving in the office between 6:30 or 7 AM, he drinks his third cup of coffee of the day, organizes his thoughts, and decides what his 3 priorities of the day will be. While some days are filled with meetings and/or projects, he sees about 25 patients each week during a 1-day clinic on Thursdays. “When I’m there, I focus entirely on that,” he said.

Patient care is a particular interest, noted colleague Cliff Hudis, MD, chief of the breast service and the institutional vice president of governmental relations at Memorial Sloan-Kettering Cancer Center in New York, New York.

“It is clear he is devoted to the well being of patients and the patient experience is always front and center for him,” he said. “He’s extraordinarily warm and caring. He gets a tremendous pleasure out of sitting with patients, talking, and interacting with them.”

Such empathy and care extends to Hortobagyi’s trainees, too. By his own estimation, he has taught more than 500 oncologists over the years, including a few dozen who “now populate the department that I think is one of the top breast cancer centers in the world, with translational research and superb care for patients,” he said. Such influence extends across the United States and around the world.

“Because of his leadership at MD Anderson Cancer Center and internationally, he is as responsible as anybody for a large cadre of doctors who work in breast cancer and other cancers,” said Hudis. “He is a model, clinically, for hundreds of people. He has had a reach that extends far beyond the walls of his office or institution. He is one of the most recognizable names in cancer medicine around the globe.”

While he has mentored many, Hortobagyi himself cites several mentors who have taught him in different ways over his life. “I used to think of mentorship as a giant who takes you under his or her wings, but it turns out there are many forms of mentorship,” he said. “Lots of people influence your career in many ways. Some are peers who unknowingly influence your career or profession, and some are ahead of you and some are younger.”

He cites MD Anderson Cancer Center colleagues such as former president John Mendelsohn, MD, and head and neck oncology physician and professor Waun Ki Hong, MD, FACP, his close friend for decades, as his own mentors. “They have introduced me to many people, and have opened my eyes to different ways of dealing with different people, and being strategic about how to conduct business,” he said.

But even patients can teach physicians. Hortobagyi cited one woman, a breast cancer patient he saw 20 years ago, who would come to see him regularly from Germany. She would ask for his clinical recommendations, but then go against them entirely, “doing exactly what she pleased.” For a decade, this continued, and Hortobagyi grew frustrated. Finally, he asked her why she would waste her time, and his, likely at great expense as she traveled to see him from Germany, to seek his insights. “You obviously don’t care about my opinion,” he said.

But to his surprise, she said he had her all wrong, she greatly respected his opinion, but that she ultimately made her own decisions about her life. “It made me understand that I can serve people in many different ways,” he said. “It is not about me telling people what to do. And she eventually did quite well in spite of not following my clinical advice,” he said.

He also counts his wife, Agnes, 62, a former fashion buyer, radio personality, and a one-time officer for the Harris County (Texas) Medical Alliance, as one of his biggest mentors, as well. They met on a blind date while in Toronto, Canada, at a conference in 1976; Hortobagyi asked her to marry him on their second date, and 6 months later, they were. “She has been a real partner,” he said. Together, they have three daughters, Zsuzsanna, a rheumatologist at Johns Hopkins University, Baltimore, Maryland; Krisztina, a human resources executive in Huston, texas; and Monica, a journalist in Washington, DC. His family has helped play a pivotal role in his success.

“I have been privileged to have a very stable home and emotional life, with full and dedicated support from my family, especially my wife,” he said. “I wonder how people who don’t have that have accomplished what they have—it must be incredibly difficult.”

With such accomplishments supported by a strong family, Hortobagyi is thoughtful about what the future of cancer research holds. “We are accelerating the pace at which we understand the biology of breast cancer and developing treatments based on that,” he said. “For much of my career, we have been using a sledgehammer to treat a fly. Now, we are at a level of a high-quality development of science that is individualized and personal. Treatments will become more effective and less toxic to patients, with a lesser effect on their quality of life. And that is just marvelous.”

He’s honored to be a part of it all, as well—always continuing to seek out opportunities to help make progress happen.

“It is an incredible privilege to spend your career doing what you want to do,” he said. “I would gladly do what I do for free, but I get paid for it. My life has been an incredible privilege, especially for the foresight of my parents—to take me out of where I was. I have great friends, great family. Without all that, I would be collecting garbage or sweeping streets and being bitter about my life.”