May 30, 2024
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I am often asked what one should do to prevent or reduce the risk of cancer. Since there are many types of cancer, with a correspondingly large number of causes, this is not easy to answer. Some solutions are simple—tobacco cessation, vaccinations for virus-associated malignancies (hepatitis B, human papillomavirus), genetic screening where appropriate. But for many important risk factors—diet, calorie and weight control, physical activity, chemical and occupational exposures—management and risk reduction, even if potentially effective, is not necessarily a pleasant thing to contemplate or, for that matter, to achieve.

A similar conundrum pervades the world of cardiovascular risk, which actually shares many of the same risk factors as cancer—obesity and calorie control, sedentary lifestyle, elevated lipids, tobacco use. And yet there has been an extraordinary reduction in cardiovascular disease mortality over the past two to three decades, far surpassing the achievements of oncology, and mostly due to prevention. This is not to downplay the remarkable advances in cardiovascular treatment—stents, artificial hearts, cardiac transplants, improved control of arrhythmias, etc.—but the enormous gains in cardiovascular mortality that have been achieved stem primarily from primary and secondary prevention—hypertension and lipid control, tobacco cessation, diabetes management, weight management, physical activity, anticoagulation, aspirin, etc.

There are two ways to achieve success with these entities. One is the hard way—by managing lifestyle—reducing salt and fats in your diet, watching what you eat, exercising and going to the gym, tobacco control. The other is to rely on a statin pill and a hypertension medication. And, in truth, it is the latter that has precipitated the success of the cardiovascular prevention enterprise. We are a society that has become pill-obsessed—it is the rare middle-aged/older individual who is not on some medication or supplement for a chronic condition.

The quest for analogous cancer chemopreventive agents really took off in the late 1980s. This endeavor sought agents, such as vitamins or minerals, which are relatively nontoxic and safe and would reduce the risk of cancer incidence. Major candidates for this included beta-carotene, calcium, folate, vitamin E, vitamin D and selenium, as well as various idiosyncratic chemicals. Another group of candidates for chemoprevention included actual medications, among them aspirin and other nonsteroidal anti-inflammatory drugs, tamoxifen and other hormonal agents, metformin, bisphosphonates and others.

The studies in this area have been generally disappointing and often confusing, with methodological issues clouding results. A popular model in which to test vitamins and minerals has been the adenomatous polyp patient. The prevalence of adenomas found on screening colonoscopy can range as high as 30%. Those who have an adenoma removed at colonoscopy have about a 30% chance of recurrence at three years. Thus, this provides many subjects and a high rate of endpoints, so that one can do a randomized trial to test a potential chemopreventive agent with good statistical power with about 800-1,000 subjects in three years. Many vitamins and minerals, such as beta-carotene and calcium, proved efficacious in reducing the occurrence of second adenomas in this setting. Nonetheless, when these agents were subsequently tested for their ability to prevent colorectal cancer, they proved ineffective. I don’t know offhand of a mineral/vitamin that has proven itself conclusively to be chemopreventive.

If one looks at the category of actual drugs, there are some agents that are effective in certain contexts. Tamoxifen or other hormonal agents (aromatase inhibitors), for example, prevents breast cancer in women at elevated risk for breast cancer from genetic or other causes. However, tamoxifen is an antineoplastic agent—on some level, the term “prevention” may be a misnomer as opposed to the term “pre-treatment.” This set of agents is recommended in those who are at elevated risk for breast cancer, but not those at average risk. And I would certainly encourage those who qualify for this intervention to avail themselves of it.

The world of chemoprevention was electrified in 2005 at the plenary session of the meeting of the American Society of Clinical Oncology when a study by Gad Rennert of Kupat Holim in Israel and Steven Gruber of the University of Michigan was presented (later published in the New England Journal of Medicine). They conducted the Molecular Epidemiology of Colorectal Cancer study, which collected approximately 2,000 cases and 2,000 controls in northern Israel to look for colorectal cancer risk factors. Jenny Poynter presented her PhD dissertation, which looked at statin use. She found that those who used statins for five or more years had a 47% reduction in their risk of colorectal cancer. Increased cholesterol has been associated with colon cancer risk so this seemed plausible. Nonetheless, critics complained that use of statins would be confounded by other protective behaviors, such as increased colonoscopy use and decreased smoking. Later studies, including a randomized trial, never replicated Poynter’s findings.

Thus, more than 30 years later, the use of chemopreventive agents remains unfortunately a limited arena and, I am sure, a disappointment to its founders. Cancer prevention, for the most part, still demands the hard work of lifestyle and behavioral change. There are no easy answers.


Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York.


This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.

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