One of the most lauded breast cancer researchers of the last few decades, Dr. Bernard Fisher led the clinical trials that proved the benefit of lumpectomy and adjuvant chemotherapy in breast cancer patients and of tamoxifen for prevention in women at high risk for breast cancer. Last month, Dr. Fisher gave a grand rounds lecture to NIH Clinical Center fellows. He talks with the Bulletin about some of the points he raised during the lecture.

You talked about the difference in clinical research between a paradigm and normal science. What is the difference, exactly?
A paradigm is a collection of all of the information - lab experiments, clinical investigation, and so forth - that governs the treatment of a certain patient population. One can have very good research and very good clinical results, but if the community of practitioners is not willing to accept this, it doesn't become a paradigm. Initially with lumpectomy, a lot of people didn't accept our work. It was only after additional studies confirmed our findings that things changed. As far as prevention is concerned, there is very good information demonstrating that tamoxifen is of benefit in women at high risk, but the drug hasn't been accepted to the point where it's in universal use.

Most people who are doing research are doing "normal science." For example, everybody agrees that part of the paradigm of lumpectomy is postoperative radiation. But the questions now are: How much radiation? Do you give it focally or to the whole breast? Do you do brachytherapy? And then people write papers and say it's a new paradigm. It isn't. It's trying to perfect the existing paradigm. Normal science is necessary, but the work of paradigms is about looking at the bigger picture.

Were you ever surprised at the results of some of your groundbreaking trials?
I was surprised about many of the things I found in my laboratory experiments. My involvement in clinical trials was not to do them as an entrepreneurial exercise. The early trials were done as an extension of what I was doing in the laboratory. It's what we now call "translational research." I think I'm one of the few people of my generation who was able to work in the lab and, at the same time, transfer the findings to the clinic and prove whether they had merit.

Can people do both basic and clinical research these days?
I think it is harder, frankly. The pace of the times in which we live makes it harder. I don't think I could possibly have done today what I did in those early years. I used to eat lunch with Jonas Salk regularly and he said it would have been impossible in the latter years of his life to do what he did earlier in his career. Today, clearly it would be even more difficult.