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A Conversation with Dr. Larry Norton on the Future of Breast Cancer Research

BCRF’s founding scientific director discusses important breakthroughs of the last three decades and those we’re on the cusp of realizing

Susan Hertog, distinguished author and BCRF board member, sat down—virtually—with BCRF Founding Scientific Director Larry Norton, MD, for a deep dive into how far we’ve come and what the future holds for breast cancer research. Here is a condensed, edited excerpt from the conversation.

I'd like to take a novel approach: beginning at the beginning. I'm always inspired by that kitchen table story where, in 1993, you and Evelyn came together at her kitchen table in her New York apartment. And you were from completely different worlds, yet it was almost magical. You told me you had a common vision.

It was an incredible time. She invited me over to her kitchen and over Darjeeling tea, we had a conversation. And I explained the structure of scientific inquiry in those days, [which] was basically a guarantee of mediocrity. It was a way of filtering out the creativity and imagination, draining the life out of the creative scientific enterprise. You need a few things to get people to be creative: First of all, you’ve got to identify the most creative people—they're not necessarily the most obvious. Then you give them two things: You need freedom, and you need security. And [Evelyn] said something else there that I think is really critically important: You need a community, because they'll be willing to work together spontaneously [and] organically, because they're not going to be afraid of somebody stealing their ideas. Within a family, you can say things that you can't say necessarily to strangers. And that community spirit will encourage their individual creativity and productivity. That first year, we raised enough money to support eight people, and we now have nearly 275 investigators throughout the world.

Looking back over these almost 30 years, what were the most important breakthroughs you saw?

That’s a very hard question, because there are whole families of breakthroughs that have all worked together. For instance, BCRF investigator Dr. Joseph Sparano led an extremely important trial that looked at just a small number of genes, just 25 genes, and how they function in cancer cells that enables us to look at a patient with a specific breast cancer and say, guess what, we know you don't need chemotherapy at all. Dr. Jack Cuzick has developed other profiles. Many other BCRF investigators develop ways of actually using that molecular information to guide individual decision making for the individual case. I mean, this is just dramatically different than it was 30 years ago. I can go on and on. This whole family of changes really emphasizes something very important about BCRF: It's not one person making one discovery. It's a lot of scientists working together.

Can you take us through the process by which basic science feeds analytic programs, such as AURORA?

The AURORA Project is a huge international effort. It involves collecting samples, collecting clinical data, sending them to central repositories to actually extract the information using very advanced mathematics. BCRF’s Mathematical Oncology Initiative is looking at very sophisticated ways of doing mathematical analysis of all this data and answering the fundamental questions about what makes cancer metastasize. The wonder of it all is that now with advances in medicinal chemistry, and with the right people, we can take those advances to develop medicines or repurpose medicines that already exist and test them because we are also working with the Translational Breast Cancer Research Consortium. It's a whole spectrum from the idea stage, from the puzzle of what we can solve to actually the doing of the science in the laboratory, from the translation of that into clinical trials to actually help people. We’re getting this community to work together collaboratively so that they share their ideas [and spark ideas]. That's really what makes BCRF so magical, and why we are continuing to make the advances that we're making.

It's tough to make predictions especially about the future. But given all the innovative discoveries and technologies you've told us about, what do you see on the horizon?

Asking what is the thing that you're most excited about is like asking, What's the most important part of the airplane? And there is no one most important part of the airplane—you need all the parts and they have to work together. And that's the nature of the scientific enterprise. That's the nature of BCRF. There's no one thing because an advancement in one area can inform another area; a failure in one area can translate into success in another area.

But having said that, we're on the verge of a revolution in biomedical science and maybe in all science. What we're starting to see is that cancer is not just a cancer cell: A cancer cell has to talk to other cells. It has to talk to blood vessels. It has to talk to the immune system. It has to talk to the supportive tissue. And all of the cells in our bodies are talking to other cells. What is now emerging is a science of connections, rather than of things.

I gave a lecture recently where I showed a picture of the Earth and a picture of the moon. And I said that [if you’re] studying the Earth as hard as you can and seeing the moon as hard as you can, you're not going to know anything about the orbiting of the moon around the Earth. The relationship between them is this mysterious thing called gravity that we can measure and that we understand a lot about mathematically, but we don't even know what it is. But mathematics can describe it, and we use mathematics to not only explain the motion of the moon but land a rocket ship on the moon. The understanding of the mathematics, together with the understanding of molecules, basic biological mechanisms about how biology works, clinical expertise involving expert doctors, nurses and scientists, but also patients and patient advocates—all of that comes together, and those connections are starting to be made. We're in a major period of transition away from studying things to studying connections between things and developing mathematics that can deal with those connections.

This is how I think we're on the verge of real transformation, in our scientific understanding of many diseases, breast cancer being one of them.

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