Preventing Cancer

Preventing Cancer

George W. Sledge, MD, FASCO

Oct 28, 2011

I’ve been traveling the last few days, attending the Breast Cancer Research Foundation’s annual meeting in New York followed by the Penn State Hershey Cancer Institute’s annual symposium.

The BCRF is one of several national volunteer organizations that raise money for breast cancer research (others include the Avon Foundation and Komen for the Cure), and their support adds significantly to the cancer research agenda. The BCRF also supports ASCO’s Conquer Cancer Foundation Awards and Grants program, including an ACRA award (given this year to my colleague Bryan Schneider, I’m proud to say).

Part of the BCRF’s two-day meeting involved scientists sharing their research at Memorial Sloan Kettering, and part involved a public presentation by a panel of breast cancer researchers at the Waldorf-Astoria. I had the chance to be part of this panel, along with Nancy Davidson, a predecessor as ASCO president and an old friend and colleague. The panel also included Laura Esserman, Neal Rosen, and Chuck Perou, giving it a broad spectrum of cancer researchers transiting from the lab to the clinic. The New York Times reporter Denise Grady served as the panel’s moderator, with the able assistance of Cliff Hudis from Memorial Sloan Kettering.

The Hershey meeting was devoted to “Prevention and Tumor Microenvironment” and included talks on prevention by Powel Brown of M. D. Anderson and Howard Parnes of the NCI, as well as several microenvironment and metastasis talks.

The public is, appropriately, fascinated by prevention questions, and no less so the researchers. What can we do to prevent cancer? What environmental toxins should we avoid? Might we be able to stave off the disease through the application of vaccines or medications?

All cancers differ with regard to etiology, and even within a specific organ one can see cancers with wildly different etiologies, with different biology coursing out of causation. A head and neck cancer caused by cigarettes and one caused by human papilloma virus act differently, though both may have the same site and histology. Teasing out causation can be complex, because life histories are complex: once I get past BRCA mutations, it is rare that I can pinpoint exactly why a particular patient in my breast cancer clinic has developed the disease.

This being said, we actually do know a great deal more about causation (hence, prevention) of many cancers. The problem is moving from knowledge to action. It has taken a generation to cut smoking rates roughly in half, despite widespread knowledge of its harms, testimony to the addictive power of nicotine.

And as for breast cancer, if I were king of the world I could reduce breast cancer incidence significantly by requiring all women to bear multiple children under the age of twenty, breastfeed them, and then become long-distance runners and teetotalers. Never mind that I would be king of the world for all of 15 minutes before my elimination from the gene pool: we actually do know what to do, we just can’t see our way to the sort of social engineering it would take.

Last year as ASCO President, I became increasingly impressed (and sometimes distressed) with the disconnect between our scientific knowledge and its appropriate application to the public health. This disconnect is particularly obvious in the prevention sphere: human beings are stubborn creatures, particularly when issues of economics and civil liberties interact with medicine.

Part of this disconnect stems from the very natural human desire to blame others. We would rather believe that some obscure environmental chemical or toxin is the problem, rather than that cigarette or risky sexual behavior or overindulgence in food and alcohol that we are responsible for, and which no one else can prevent. Doctors are not epidemiologists, and rarely wish to blame the victim, even when we know the cause. This is humane and decent. We treat the disease (and patient) in front of us, not the decades of behavior that led to the disease. But if we do not address causation, who will? And how? Oncologists have a particular responsibility in the area of secondary prevention, and this certainly requires our intervention in lifestyle modification.

We often try to find a technologic fix. I suspect that the desire for cancer prevention vaccines comes from a deep longing for a “one and done” solution to the cancer problem. Scientifically there are instances where this makes real sense (cervical cancer and hepatoma), whereas in other cases (breast cancer, lung cancer, colon cancer, and many others) the lack of a clear viral etiology and the immense heterogeneity of the diseases may well doom this approach to failure.

But it is certainly worth attempting to find such fixes, because at the end of the day they seem less difficult than the societal fixes. Pellagra, a disease I have never seen, used to kill thousands of Americans each year, and afflict hundreds of thousands more. Even though the solution was obvious scientifically (eat a balanced diet), the disease was not conquered until the discovery that brewer’s yeast was full of the factor (eventually discovered to be niacin) that could rapidly reverse the course of the disease. Sometimes the technical fixes are that simple, and when they are you can ignore the underlying social issues that represent the ultimate cause of the disease.

The technical fixes have not been easy. Niacin beat pellagra, but vitamins have a checkered history in breast cancer prevention. A famous study performed in Finland in the 1990s (the ATBC trial) demonstrated an 18% increase in lung cancer risk for beta carotene supplementation, and the recently presented SELECT trial showed similarly depressing results with Vitamin E supplementation.

As for other drugs, 5-a-reductase inhibitors appear to select for high-grade prostate cancers even as they reduce overall prostate cancer by a quarter: do we want to trade fewer prostate cancers for worse prostate cancers? And while we have two FDA-approved agents for breast cancer prevention (tamoxifen and raloxifene), neither has been embraced by the physicians who would need to prescribe them if they were to have any real population benefit.

I suspect we will need something beyond technical fixes for many cancers. The childhood obesity epidemic sweeping the country will inevitably become a cancer problem, just as smoking continues to kill and just as drinking too much increases one’s risk for several cancers. Telling people to eat right, to exercise, and to quit smoking and cut down on drinking remain the cheapest and best way to prevent cancer mortality.

What is the role of the oncologist in all this? I’ve mentioned secondary prevention, but the reality is that primary prevention will require far more than the good will or even strong efforts of medical oncologists. We need the assistance of primary care physicians, and of those organs of information most influential in generating longstanding public awareness, and of politicians capable of supporting the public health. And that is the real challenge: not PI3K inhibition, nor Treg cells, but public health interventions carried out with passion over long periods of time.


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