We know the age-old expression: We are what we eat. So, how does diet affect or reduce the risk of breast cancer or how breast cancer progresses? And what non-lifestyle choices should one consider when looking to reduce their risk?
Dr. Graham Colditz, a BCRF investigator since 2004, has spent decades diving into these questions and more. Dr. Colditz is an internationally recognized leader in cancer prevention and one of the one of the most highly cited medical researchers in the world.
Not only has Dr. Colditz published more than 1,100 peer-reviewed publications and six books and earned numerous awards, but he’s developed the widely-cited website, Your Disease Risk. At Washington University in St. Louis, he is deputy director of the Institute for Public Health, the Neiss-Gain Professor in the School of Medicine, chief of the Department of Surgery’s Public Health Sciences division, program director of the Master of Population Health Sciences degree, and the associate director of prevention and control at the Siteman Cancer Center.
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Chris Riback: Dr. Colditz, thank you for joining. I appreciate your time.
Dr. Graham Colditz: My pleasure being with you today.
Chris Riback: So, I read a write-up about the impact you seek to make through your career and area of focus. And the first sentence of that impact statement reads, “It is estimated that nearly a third of breast cancers could be prevented by lifestyle choices, particularly those that support and maintain a healthy weight, including diet and exercise.” And I confess that made me feel really good and somewhat not so good. The not so good maybe is obvious. The sadness that so many people suffer based not purely on genetics, but rather lifestyle choices. The good part: it would seem that cancers resulting from lifestyle choices can be preventable through the help of scientists like you and personal actions. So help me please doctor, should I be feeling lousy or hopeful or both?
Dr. Colditz: Oh, I think both. And I can say a little for both in that it’s clear some of our risk can be set fairly early in life. And so we are not thinking about cancer as children or adolescents, so that’s maybe personal choices, peer pressure, and so on, that changes a little how much control we may have. But at the same time factors later in life that we do as adults and free-living have definitely more control over, whether we have complete control, whether the social-political environment we live in doesn’t tax alcohol, as much as you and I might want it to be taxed to cut down our easy access.
Chris Riback: Access. Yes, sure.
Dr. Colditz: Yes. But it’s that spirit.
Chris Riback: Understood. So help me, if you would level set on the science and how one derives conclusions out of an area where again, for an outsider, one can hear the numbers and you want to understand, so how does one actually get to those numbers? We can get to some of the root causes and effect. So, you derive the statistics, and I’m curious how one does that generate a statement such as, “It is estimated that nearly a third of breast cancers could be prevented by lifestyle choices.” What is the scientific discovery process look like? How do you “prove” that? And to what extent? How do you factor out or consider the role that genetics play and to what extent they’re tightly connected to so-called lifestyle choices, like healthy weight? Sorry, there’s a lot there.
Dr. Colditz: Yes. Unpack decades of works. Right.
Chris Riback: Yes. In 30 seconds, if you could, and if you could give a clean in and a cleanout that would really help.
Dr. Graham Colditz: Yes. So, the simplest concept of this would be to identify a set of say, women in this case [since] we’re studying breast cancer, who are at very healthy lifestyle: healthy diet, say no alcohol, average weight. [We] follow them over time and follow a group that is high risk: heavy drinking, overweight, and so on. And we can compare the difference in the risk of breast cancer between the two groups and do the arithmetic to estimate what proportion is avoided by following the healthy lifestyle. Then you raise genetics. So, we have to then factor in family history, say, and we can look in women with no family history and see these same effects. So the statistics and the inference from both the human data there often to get to the cause and prove words that you were asking. We want to see bench science, animal models, other hormone levels mechanisms that actually support the association.
So, when we look at alcohol and breast cancer, the International Agency for Research on Cancer concludes that alcohol causes breast and a whole range of other cancers. They’ll look at the human evidence [and] the animal and other sources of evidence to lay out a mechanism as to how alcohol is actually causing cancer and how it’s doing that in the breast.
Chris Riback: And as you go through that science, and so much of your work caught my attention, but this component that choices made even in childhood and adolescence can impact a person’s future risk of breast cancer. To exaggerate the point, it can get hard to get an adolescent to stop watching TikTok, to do homework, do the next day. How do we start to talk to [our kids about this]? How does one convince her to sleep more now to help prevent breast cancer in 20 years?
Dr. Colditz: So, you’ve hit a really important point that a lot of the lifestyle in childhood and adolescents won’t be framed in terms of just breast cancer risk. It’ll be for your health, for your future health and adolescents aren’t always so future-oriented, as we know. But you’re totally right, that again, studies show diet and physical activity—physical activity particularly, say, between ages 12 and 20—actually can have a lifelong impact. So how do we have a society that supports that, rather than thinking it’s just TikTok. Or just the mode of transport so we have access to safe exercise. All of these things I think come together and that will reduce risk of diabetes, heart disease, and stroke, as well as what we’re after, which is breast cancer. Because we don’t have the same range of options for prevention for breast as those other conditions I mentioned.
Chris Riback: There’s one area of your study and please, correct me if I’m misinterpreting this, that also struck me. The benefits to adolescents of eating nuts. Why are nuts such a big deal for adolescents to eat?
Dr. Colditz: That’s a super question. Interesting thing here is that we can look at diet, fruit, vegetable, fiber. Nuts come through as clearly reducing risk. My colleagues at Harvard had studied nuts in relation to other diseases, right. But the assumption at this stage is still that nuts are uniquely good at changing your metabolic profile. And that this in fact then is translating through to breast cancer risk. I don’t think we’ve got all the fine details of mechanisms nailed down, but it’s consistent across multiple studies. And again, fairly simple part of lifestyle, if you will.
Chris Riback: And another area into which I understand you plan to dive deeper: how modifiable factors such as diet affect or reduce the risk of breast cancer, including how those factors affect the rate of transition between breast cancer stages, such as the progression from benign breast disease to breast cancer. Where are you on that work? I couldn’t fully determine whether this was a gleam in your eye or whether you were deep into the research. So tell me about this please.
Dr. Colditz: Very cool. We’re actually writing a grant literally as we speak but over multiple weeks now, to really further understand which factors are impacting sort of, if you will, the age at onset of the first lesions, the premalignant changes, and which factors are driving subsequent speed of growth, transition from benign lesions to invasive or in situ and then invasive disease. And the irony in much of our insight on prevention is that we don’t always have a very good sense of the timeline of when a change in lifestyle will actually finally translate to our risk. Okay, for smoking cessation and heart attack, we know that’s a very short cycle, but obesity and cancer, [there are] lots of different ways that this can be changing risk. And so it will help us focus and identify who’s going to benefit most from the changes for prevention.
So grant pending, colleagues working with me on statistical methods to improve the way we can look at this. Building on our premalignant lesion repository that we’ve got. So there’s a number of ways to come at this. So it’s moving, maybe not as fast as we’d all like, but it’s beyond just a glimmer.
Chris Riback: Picking up though, just on one of the elements that you said: What inspired the choice or the decision that there is a need to look at that? Was there a gap perhaps in data that you had noticed? Was there new data that came across or was this an area that you or colleagues had always wanted to look at, but now just it so happens that the time is right?
Dr. Colditz: No. So, one of the concerns I’ve had with recommendations about prevention—going back 30 years of teaching on this—is that we often end up with recommendations, if we act now we can halve cancer mortality in 10 years. And you’re like, “Really?” Is it all going to change that quickly? Right. Our sense to engage people where they’re at with the level of risk they’re at, we have to have realistic sense of what change will lead to risk reduction [and] over what timeframe. And that just trying to bring more clarity to that is really motivating this. And so it is right in front of us to be done still.
Chris Riback: One more question on the science components, and then I want to get into… Yes, I have the privilege to do a number of these conversations. And in preparations for this conversation, I did get many questions around the, well, what should I do here? What should people do here? So, yes, as you know from the questions that I know you get peppered with all the time, people do want those tips from you. So, I’m not going to let you off the hook. I am going to at least ask you for those tips. But one more question to connect really the science, the biology, and the behavior. How does something like obesity or diet or sleep, even connect with something as specific as breast cancer? What is that path? How do those dots actually connect?
Dr. Colditz: So, let’s take obesity after menopause, and for weight gain, which of course is the trajectory most of the world is on. We know that the more overweight a woman is the higher her estrogen levels are—estrogen active, if you will—as a fertilizer for cell division and cell division can lead to even more genetic damage accumulating, right? So that one is in fact, very, we’ll say simple, and we can compare U.S., Japan, other countries that have different weight gain trajectories and see a substantial portion of postmenopausal breast cancer can really be explained by this higher obesity, higher hormone exposure, and higher breast cancer.
Chris Riback: Now to get back to putting you on the hook. We got a number of questions that folks would like in terms of helping guide their personal behavior. I imagine that you might have various caveats, please feel free to let me know about them, such as each of us is different. And each of us should discuss our personal situations with our personal physicians. And the other caveats please add, of course. But if I could ask you some of these to begin, are there any foods that are proven to reduce your risk of breast cancer? Is there such a thing as a breast cancer-fighting food or a breast cancer diet, even?
Dr. Colditz: Not a specific food, but the fruit and vegetable cluster still is probably the most promising part of diet for prevention of breast cancer.
Chris Riback: And you just mentioned estrogen a moment ago. But what’s the link between estrogen and the food that you eat? Are there foods that can lower or increase the estrogen in your body? Because you’ve already talked about the effect that estrogen can have in terms of risk of breast cancer.
Dr. Colditz: So, the challenge for the foods lowering estrogen really comes down to separating out the foods and weight, right? But the potential is there for a higher fiber diet to actually be helpful in the steady hormone status. Higher physical activity is probably working in that direction too. But a specific food is not going to change hormone levels up or down on its own. Maybe alcohol has some impact separately where it’s a chemical agent if you will. That’s very different from trying to think across all the foods I eat, which chemical am I getting with alcohol? We actually know what we have. Yes.
Chris Riback: You’ve mentioned alcohol a number of times, but is that primary or close to primary on your mind in terms of things that you worry about in terms of lifestyle choices?
Dr. Colditz: Both in terms of lifestyle choices and how we could counter its effecting the breast. Yes. For a long time, we’ve puzzled over whether there are the equivalence of the vitamin you could take that would counter the effect of alcohol. We have colleagues who say, “Well, just stop everyone from drinking.” And it’s like, I think we tried that as a nation once, right?
Chris Riback: Yes.
Dr. Colditz: And we know that adolescents and college-age women have caught up to men with their alcohol consumption. So the trends are probably going in the wrong direction for breast cancer. So, what are the potential ways to A) control the amount of consumption and then B) if there are women who are continuing to drink, how do we find strategies to counter that effect? And that’s still an open question.
Chris Riback: What about breastfeeding? Does breastfeeding “prevent” breast cancer? What do researchers know about the link?
Dr. Colditz: Yes. So, we’ve looked at the analysis of all the published studies and definitely there is a reduction in risk for women who have breastfed, and the longer they’ve breastfed the lower their personal risk. This relates to changes in the breast tissue that are in fact, a consequence of breastfeeding. The good news is there’s benefit. Again, the bad news, our social structure, there are workplaces where breastfeeding is really hard, if impossible. And so we can think of this as, yes, it may be an option for some women. It’s not, I would say, an option for every woman given her work and social circumstances. So, you could argue collectively we should be providing more support for breastfeeding if we care about this as a nation. But yes, the changes in tissue, lifelong benefit, more is better in this case, even though, as we have fewer and fewer children that is diminishing returns.
Chris Riback: Yes. Population demographic changes are very, very significant. I think the last question I have on the tips from Dr. Colditz section of this conversation. You mentioned exercise, of course, and we all hear, read about all the ways in which exercise, even very little bits of exercise can be beneficial. Any other non-lifestyle choices that someone should consider to reduce their risk of breast cancer?
Dr. Colditz: I would put in there as well, avoiding further weight gain rather than thinking we’ve all got to go back to whatever weight we were in high school or somewhere that is, we’ll say, largely unattainable. If we all avoided more weight gain in 10 years’ time, the nation would be leaner than if we all kept gaining one to two pounds a year. And so setting a monitoring—self-monitoring scales and paying attention to weight—rather than what we may do as a nation, [which] is new year’s resolution, try to lose weight, give up, gain it back. It’s a seesaw that keeps going up.
Chris Riback: What an excellent way to frame it. So the idea of losing weight, getting back to that college weight or whatever is so intimidating. It makes it so easy to give up. Instead, to frame it as. Just maintain. It’s much more attainable, just much easier to consider. Tell me about the Your Disease Risk website. What is it? How should people use it? What kind of impact does it have? Is its impact educational or on actual behavior?
Dr. Colditz: Oh, that’s really great question. So quick summary, the website was developed over 20 years ago with a goal of helping people understand that cancer is preventable. The thought process in the 1990s if we can go back that far before COVID. Sort of this, well, there’s nothing I can do. And we put the evidence together, worked out how to communicate that to the general public and developed a tool that is engaging and offering tips and strategies to adopt changes in lifestyle that can lower risk. And so, it’s used. It’s engaging and really takes account of where you are at now in your risk factor profile as to suggestions for changes. The ability for it to transform people’s behavior overnight just by using the tool once is wishful thinking.
Chris Riback: Yes. Yes.
Dr. Colditz: But definitely, it’s been used in studies by colleagues, either a component of it, or more to promote more discussion with your primary care provider about risk and risk reduction strategies—things like this that show it actually is engaging women, and having them engage in more discussion of prevention. I think they’re all steps towards successful changes to lower risk. And there are certainly people who come back multiple times. So lots of pieces to support that it’s beneficial, but we can’t say, if you go use it tonight, by the end of the month, you’ll have moved your risk down.
Chris Riback: Well, you do understand doctor, we live in a time of immediate gratification. If not by the end of the month, certainly by the end of next month. You can guarantee that, right?
Dr. Colditz: There you go. There you go.
Chris Riback: Thank you. So it is hard to have the privilege of getting to talk with you and not also ask about your landmark work from now more than 25 years ago. You helped identify the increase in risk of breast cancer with the use of combined estrogen plus progestin therapy and a significant increase in risk with increasing duration of use.
Dr. Colditz: Yes.
Chris Riback: You also showed that mortality from breast cancer was also elevated among current users. How do you look back now on that work and the incredible impact that is made?
Dr. Colditz: That’s a super question, and it’s gratifying that the results held up. The Women’s Health Initiative trial held up and in further evidence that’s accumulated [in the] UK and elsewhere. The continuing current use is the real driver back at our earlier question. When you stop using that combination, risk starts to fall back to where it would’ve been. So, there’s a real effect—it’s reversible in large part. And while the manufacturing industry for tooth and nail to, if you will, discredit some of this and assemble data that contradicted what we and other studies obviously showed. The trial stopped early, therefore it must have been wrong. Well, it stopped early because the stopping rule said adverse breast cancer was a reason to stop, right? So people can twist this, but to me it highlights, again, the good data focused on breast cancer can really help understand how the disease process is modifiable. And so we should be continuing to push for other ways to modify this risk.
Chris Riback: Wow. It’s incredible impact to so many people over such a period of time. It’s wonderful. If I could have the benefit of embarrassing you further. I’m curious about where you are now versus your expectations coming into your profession. You grew up in Australia. And as I understand it, growing up, you enjoyed your share of cricket and rugby. And now besides the individual impact you’ve made on individual lives. Do you happen to know what the h-index is? Do you know about that?
Chris Riback: Yes. For listeners who aren’t aware, it’s an author level metric that measures both the productivity and citation impact of the publications initially used for an individual scientist or scholar. According to Google Scholar statistics, you have the highest h-level index of any living author. I can only assume that that was your exact expectation set as you got into this, wasn’t it?
Dr. Colditz: Not at all. And it’s a moving target, who’s at the top. Right? But it’s a great question. In med school, I really wanted to do prevention. I did oncology rotations where you had lung cancer patients that clearly had been smoking. And we didn’t talk about smoking cessation in med school, right? And then you do another ward with women with ovarian cancer, and we had, at that point, no idea what’s causing ovarian cancer. And that hands-on experience really pushed me to ask, why aren’t we doing more to prevent this pretty horrible set of diseases? Lung, ovary, breast—my sister-in-law died of breast cancer in her 20s. So it’s really dramatic to see we’ve made a lot of progress. It’s still challenging that there’s so much more to do. But as a med student, it was, I just want to go and some prevention and my mom was upset, I didn’t come back to Australia after I finished my PhD.
Chris Riback: Can’t blame her for that. Factually, she was right. What do any of us want to do? We want to make impact in whatever chosen profession and to have done that and to have that double benefit of knowing that you’re making impact on individual lives, personal lives, but that also it’s getting amplified because it’s being cited, because in the metrics around how it’s being cited. When I came across that fact about you, it just struck me that, that must be a double or even somehow exponential level of satisfaction. Because you’re getting to make impact beyond yourself. It grows through others citing your work. And that’s a nice thing.
Dr. Colditz: In a real way; the mentoring junior colleagues and supporting them is another. We don’t have an index for that, but that is part of the power of this, that the number and range of people and the skills that are coming to prevention clearly has grown over time. And yes, the work is cited, but we’ve got to also move it to the next level to get the changes in behavior.
Chris Riback: Of course. We’re not going to let you rest on your h-index doctor, you know that.
Dr. Colditz: Thank you. Thank you.
Chris Riback: Yes. We’re not stopping there. To close out, if you would, what role has BCRF played in your research?
Dr. Colditz: Well, they’ve been an amazingly steady support for our work, and I will say unique support for our work to look at this childhood and adolescent exposures and breast cancer. We’ve tried to get NIH funding for this on and off over the years. And the peer review process is skeptical of that. But BCRF has been there through the whole of this, and if you look we’ve contributed substantially to the literature on the adolescent diet activity and so on, early on that others have then tried to replicate in other studies. And BCRF was in there at the beginning of this and to this day continues to support us to build on both the adolescent piece, but also now more on the premalignant lesions and how they progress and what we can do to modify that. So, we wouldn’t be where we’re at without that support over the years.
Chris Riback: Well, that’s kind of you, and I’m sure that what folks would like now is for you to get back to the grant writing, figure out this leisure thing, and keep pushing your h-index and the impact that you make. Dr. Colditz, thank you. Thank you for your time. Thank you for the work that you have done throughout your lifetime.
Dr. Colditz: Chris, thank you. It’s great to be here. And thanks to BCRF for all the support.
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