Web Exclusive: Q&A with Dr. Dennis Slamon

Dennis Slamon, MD, PhD, talks about his involvement in the history of Herceptin.

Talk about this article with other patients, caregivers, and advocates in the Breast CURE discussion group.
Dennis Slamon, MD, PhD, talked with CURE’s Elizabeth Whittington about his involvement in the history of Herceptin. A full transcript of their conversation follows.

Why was your HER2 research considered non-traditional at the time?

A lot of places were still using traditional approaches to treating cancer, which was to use various chemotherapeutic drugs and radiation—essentially poisons of one type or another—in the hopes of killing more bad cells than good cells. It was a one-size-fits-all approach for a lot of different cancers. All cancers within a classification essentially got the same chemotherapy regimen, but it became clear that the outcome with those regimens was very different. Some patients did very well, but many did very poorly. And once the patient had metastatic disease—meaning the disease traveled outside the primary site and beyond where the surgeon could remove it—then the patient almost always succumbed to the disease. Using chemotherapy really didn’t make an impact on survival at that point. So, a number of groups were frustrated with that and thought about backing up and beginning to study the basic science of the cells to see what converts a normal cell to a malignant cell to see if we could treat that specifically.

Why did you choose to research breast cancer and HER2?

We didn’t specifically choose breast cancer or HER2; what we specifically chose to do was look at all the major cancers. We began to study the DNA from those cancers and ask what gene or genes might be broken in them. We specifically looked at genes that would likely be regulating growth because essentially cancer is an abnormality in growth regulation of cells. In ‘84 and ‘85, the genome hadn’t been sequenced yet, so there were only a handful of genes that were really known to be bonafide genes that played a role in regulating growth control. We had banked away a lot of different types of tumor specimens and extracted the DNA, the genetic blueprint, from all those different tumors. We looked at the genes that were known at that time and looked at the DNA of all these different tumor types to see if we could find anything grossly broken using what is now pretty primitive techniques. When we got to the breast cancer specimens, we found that this gene HER2, which was a growth factor receptor, was broken in about 25 percent of breast cancers.

Once we identified that 25 percent of the women had this problem and identified that these women had a more aggressive form of the disease, the next question for the lab became why. Is it simply a flag of aggressive tumors or is it associated with bad-acting tumors because it’s playing a role in causing them. The next stage of the research was to engineer cells to have the HER2 broken. When we did that, we saw that they formed tumors more readily in mice, that the tumors were more metastatic, more aggressive—all the hallmarks of what we were seeing in the patient. When we proved that targeting HER2 using antibodies reversed the effect, we were ready to go to clinical trials. Again, the skepticism came up, that antibodies wouldn’t work because they hadn’t worked in the past. The first trials started in earnest at UCLA in ‘91-’92 where we first tested the antibody in humans. At that time, a fully human antibody had never been put in humans before, so we had to prove that it was safe. After we showed it was safe and we saw modest activity, we did a definitive trial where we compared it against the best available standard therapy and we proved it was superior.

Did you have any difficulty recruiting for the larger trials?

Initially, absolutely we did. Word was not getting out about the trials. Doctors who heard about it really did not think it was going to make a difference. Ultimately, the National Breast Cancer Coalition helped out and made a big impact by making their members aware that there was this subclass of breast cancers called HER2-positive that behaved differently than other breast cancer. The NBCC helped drive patients to look for the trial or ask their doctors about it.

How did Genentech, the eventual manufacturer of Herceptin, get involved?

Genentech was always involved from the standpoint that one of their scientists was among one of the first who cloned the gene. Our lab was the one that showed that the alteration of this gene was particularly present in these aggressive breast cancers and we told Genentech of this data. At the time, the company overall wasn’t interested, but there was a small core of scientists who felt this was interesting and worth pursuing. The precedent for antibodies was poor and a lot of the people thought this was a waste of time, but that small core within the company stuck with us and colloraborated with us through the early stages and that’s how Genentech became the company that ultimately made the drug.

Did the initial skepticism surrounding your research make your work difficult?

Talk about this article with other patients, caregivers, and advocates in the Breast CURE discussion group.
Cure Connections
Related Articles
Alternative Treatment Options: What's Worked for Me
Traditional treatment options for breast cancer include surgery, chemotherapy, radiation and anti-hormone therapies but there are other options available.
Unhappy During Pink October
Cancer is more than cancer awareness and it isn’t just about the “popular” cancers.
Reflections From a Breast Cancer Survivor on 'Pinktober'
Every October, pink ribbons appear to signal the start of Breast Cancer Awareness Month. Pink has become the color of breast cancer, but some survivors don't like the color pink and they have a good reason for feeling the way they do.
Finding Calm in the Face of Cancer
An easy-to-use list to stay calm when the cancer panic hits.
Chemo Brain: A Breast Cancer Survivor's Commentary
Two-time cancer survivor struggles living with chemo brain.
Related Videos
Amanda L. Kong on Seeking a Second Opinion for Breast Cancer Care at a High Volume Hospital
Amanda L. Kong, discusses why patients should consider seeking a second opinion for their breast cancer diagnosis and care at a high volume hospital.
Amanda L. Kong on Breast Cancer Care at High Volume Hospitals
This study sought to identify patterns of breast cancer care at high volume hospitals.
Anees B. Chagpar on What to Expect After Contralateral Prophylactic Mastectomy
Anees B. Chagpar, director of the Breast Center at Smilow Cancer Hospital at Yale-New Haven, discusses what a patient can expect following a contralateral prophylactic mastectomy.
Anees B. Chagpar Provides an Overview of Contralateral Prophylactic Mastectomy
Anees B. Chagpar, director of the Breast Center at Smilow Cancer Hospital at Yale-New Haven, provides an overview of contralateral prophylactic mastectomy.
Sara M. Tolaney on Neoadjuvant Treatment Considerations for Triple-Negative Breast Cancer
There are many clinical trial opportunities, Tolaney says, before surgery.