Medicine Is in His DNA: Giant in Breast Gene Research Draws on Childhood Values

Beth Fand Incollingo
Published Online: Wednesday, May 11, 2011
Dennis Slamon
A Conversation With Dennis Slamon, MD, PhD

Plenty of children are afraid to go to the doctor. Dennis Slamon used to look forward to it.

“A career in medicine was what I wanted since I was 5 or 6, simply because of the remarkable doctor who took care of our family,” said Slamon, remembering the pediatrician who made house calls to treat him for a cold or flu. “He was very caring, very gentle, and very effective. I thought it would be great to be able to help people like that and make a family feel so good.”

Slamon, 62, the son of a coal worker and a homemaker, not only went on to become a physician, but also has realized his dream of helping people—hundreds of thousands of people, in fact. That’s how many patients have been treated with Herceptin (trastuzumab), the first molecularly targeted therapy for breast cancer.

During nearly 40 years spent researching and caring for patients, Slamon, now director of Clinical/ Translational Research at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles (UCLA), conducted the lab work and testing that resulted in Herceptin.

And when it comes to bedside manner, Slamon has lived up to his ideal, said Barbara Bradfield, the first patient to take Herceptin in phase I trials 19 years ago.

When Bradfield initially declined to take part in the trial, she said, Slamon called and begged her to reconsider.

“He worried all night, and he called me the next morning and asked me to go talk with him,” said Bradfield, who has had 12 tumors but has remained cancer-free since completing the trial. “When we met in person, he was so convincing. He’s got these beautiful, brown, soulful eyes, and he spent an hour and a half going through slides explaining everything, so I ended up saying yes—thank goodness.”

HER2-positive tumor cells

The orange staining shows HER2-positive tumor cells. Courtesy F. Hoffmann-La Roche Ltd.

Long Battle, Long Hours on Path to Herceptin

Approved by the FDA in 1998 and manufactured by Genentech, now part of the Roche Group, Herceptin is a monoclonal antibody that helps counteract a mutation of the HER2 gene, found in about 25% of breast cancer patients.

The intravenous drug, given in combination with or following chemotherapy, reduces recurrence rates by half in specific types of early HER2-positive breast cancer and by one-third in metastatic HER2- positive breast cancer, Slamon said. It increases survival by about 35% and 30% in those early and metastatic HER2-positive breast cancers, respectively, the researcher said.

The drug, which doesn’t cause such adverse events as the hair loss and nausea that often accompany conventional therapies, was also approved by the FDA last year for use in HER2-positive metastatic stomach cancer, in combination with chemotherapy.

Slamon fought for 12 years to get Herceptin to patients, keeping the project alive despite a nearly crippling early lack of funding, and ultimately helping to spark an understanding that breast cancer and other cancer types can take a variety of forms, each subtype potentially requiring its own treatment options. It is a principle that will prove true in all other major malignancies, Slamon believes, as the recent rise in targeted cancer therapies picks up speed during the next 5 years.

“We followed the data, and if it’s there and it says your approach is right, it doesn’t matter what anyone else’s preconceived notion is,” said Slamon, who has won nearly 2 dozen national research awards for his work during the last decade. “We never gave up when people said we were wasting our time.”

“We followed the data, and if it’s there and it says your approach is right, it doesn’t matter what anyone else’s preconceived notion is. We never gave up when people said we were wasting our time.”

Slamon is continuing his fight against cancer through his roles at UCLA, where he spends nearly half his time reviewing data and considering where it might lead.

“The highlight of my day is to meet with mid- and junior-level investigators and see this new stuff,” he said. “With colleagues capable of pushing the agenda in a positive way, we can think about exciting ideas.”

Serving as chief of UCLA’s Division of Hematology-Oncology and also a professor of Medicine, Slamon devotes about 30% of his hours to administrative duties, including raising money for research, another 20% to seeing cancer patients, and the remainder to teaching and giving lectures offsite.

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