Friday, November 25, 2016

An interview with our cousin Peter Greenwald MD PhD

Peter is the director of the Division of Cancer Prevention at the National Cancer Institute (NCI). His father was the brother of Grandma Rose (Greenwald) Buckwald.

My memories of him at family gatherings are of a sweet, caring, humble man, much like another doctor in the family, Murphy Rothman.

Peter Greenwald,MD, PhD

JOP: How can community oncologists get involved in cancer prevention?

There are two broad approaches to prevention. One is a lifestyle approach—live a healthy lifestyle, and you can lower your chances of getting cancer. And the other is a medical approach.

For lifestyle, the best thing oncologists can do is lead by example. Keep trim themselves, get exercise daily, eat primarily a plant-based diet, don't smoke, and advise patients and their family members to do the same thing. Oncologists can also be community leaders, which many are. Obesity is a significant problem now that increases cancer risk as well as the risk of other conditions, and we have to address that as a society. We have to make it easy for people to walk and exercise safely in their communities. Oncologists can work with city planners to create parks and safe places for children to get exercise through outdoor play or riding bicycles, and work with the community to encourage that, instead of sedentary computer games. Oncologists can also work with school systems on diet and exercise.

Medical prevention is an exciting field that is moving fast. The most important thing oncologists can do to keep up is to take part in clinical prevention trials. There's no better continuing education method. NCI sponsors major clinical trial networks such as the Community Clinical Oncology Program [CCOP], which involves more than 400 hospitals and 3,600 physicians working on some 70 active prevention and control trials. Another is the National Surgical Adjuvant Breast and Bowel Project [NSABP], one of the NCI-sponsored cooperative groups, which has nearly 100 research sites in its network and was responsible for the recently completed Study of Tamoxifen and Raloxifene [STAR] trial. You can become part of the CCOP network or forge a tie to a cancer center or a university center.

JOP: What medical approaches from completed trials can community oncologists incorporate today?

You can prevent half [the incidence] of breast cancer in women at increased risk right now with the selective estrogen receptor modulators [SERMs] raloxifene and tamoxifen. Oncologists know about and use tamoxifen based on the results of the Breast Cancer Prevention Trial [BCPT], which showed that the drug reduced the risk of breast cancer by about half in those who took it. Some 70% of breast cancer is estrogen-receptor–positive, and in the BCPT, about 70% of those cancers were prevented.

The recently completed STAR trial compared raloxifene head-to-head with tamoxifen in 19,471 postmenopausal women, based on the possibility that raloxifene might give the same benefit as tamoxifen without as many adverse effects. And that's what happened. Raloxifene was just as good as tamoxifen at preventing invasive breast cancer, although it was not as good at preventing noninvasive breast cancer, such as ductal and lobular carcinoma in situ. But the raloxifene patients had only about 60% as much endometrial cancer, fewer pulmonary emboli, fewer cataracts, fewer deep-vein thromboses, and about the same number of strokes and fractures. Women will start asking about these drugs, so oncologists should know about the results of these trials, and they will be able to advise patients about raloxifene as soon as this is reviewed and approved by the FDA [US Food and Drug Administration]. This is also an excellent opportunity for oncologists to collaborate with primary-care physicians in their communities as women initiate discussions about their risk of breast cancer.

Another large trial completed in 2003 hasn't given clear public practice information, but research is in progress to better understand its outcomes. The Prostate Cancer Prevention Trial was also run by a cooperative group, the Southwest Oncology Group. In a double-blind study, a little over 18,000 men (including me) took finasteride or placebo for 7 years. There was a one-quarter reduction in the rate of cancer on biopsy, which was performed if PSA [prostate-specific antigen] rose or a digital rectal exam showed a nodule during the trial and at the end of the intervention, when both those on finasteride and those on placebo had biopsies, regardless of their prostate-specific antigen levels. However, the men who had positive biopsy results tended to have slightly higher-grade or more aggressive-appearing cancer. Now, studies are ongoing to determine whether that is in fact the case or an artifact; so it's still research in progress.

JOP: Although many nutrition and lifestyle trials aren't complete, patients are often anxious to incorporate those types of changes now.

And they should be. There are already some hints. For example, the Women's Intervention Nutrition Study [WINS] completed last year suggested that breast cancer survivors who reduced the amount of fat in their diets were less likely to have a recurrence. Community oncologists should at least know something about nutrition and lifestyle effects and should also find out if there are opportunities in their area to refer to people who can really help their patients accomplish those things.

Even though the Selenium and Vitamin E Cancer Prevention Trial [SELECT] isn't complete, previous studies hinted at the potential of selenium and vitamin E to prevent prostate cancer, making the case for testing this idea in a large clinical trial. In this trial, 32,000 men are receiving vitamin E or selenium or both, or placebo. Because the end point is clinical prostate cancer, it will be a few years before we know the results.

JOP: What other avenues look promising for preventing the most common cancers?

In colorectal cancer, screening can be prevention because there's evidence that 70% to 90% of these cancers can be prevented if you find and remove polyps. The problem with the current methods—colonoscopy or sigmoidoscopy plus occult blood testing–is that few people want to do it. More than 60% of Americans age 50 and older have not been screened appropriately.

One research approach that is noninvasive and doesn't require the preparation that many people find objectionable is to test DNA in shed cells in the stool for certain mutations that are known to be associated with polyps or colon cancer. The potential tests aren't yet sensitive enough, so research is aimed at improving that.

In prostate cancer, one of the biggest challenges is to differentiate indolent cancers from those that are going to be aggressive and potentially fatal. An important research direction is looking at the molecular signatures and other characteristics of prostate cancer cells that might differentiate them.

We know that most cancer of the cervix is attributable to infection with certain types of human papilloma virus. Vaccines to prevent those infections are being field tested now. [Editor's note: On June 8, 2006, the FDA announced licensing for the sale of a vaccine for the prevention of cervical cancer caused by human papillomavirus.]

In breast cancer, the next study will likely be of an aromatase inhibitor, which, rather than competing with the estrogen receptor like the SERMs, inhibits estrogen production. Studies have shown that women with early breast cancer who took aromatase inhibitors had fewer new cancers in the opposite breast than women treated with tamoxifen. A clinical trial is needed to determine whether we can do even better in preventing hormonally driven breast cancers. But our studies also have to look at the balance of benefits and risks because all of these drugs have some side effects. We have to understand that balance so that women, with their physicians, can make informed decisions. For example, someone with a family history of breast cancer may do one thing, and someone with a family history of heart disease or osteoporosis, something else.

JOP: When these and future studies bear fruit with more effective cancer prevention, will the need for oncologists shrink?

No. Instead, the scope of the field of oncology will change, in much the way cardiology has changed to risk assessment and management (for example, looking for risk markers such as high blood pressure or high LDL [low-density lipoprotein] cholesterol and bringing that risk down). In 5 to 10 years, we think risk assessment and management are going to be a major part of oncology practice. To get there, we have to validate the markers and prove that modifying them changes the risk—a research direction in itself.

With new tests, we may identify people that have a risk without apparent disease, similar to high blood pressure. But we'll also be identifying people who have precancerous lesions, so oncology practice will also need to shift toward treatment of precancer to prevent progression or to cause regression. Those trends may mean that a broader group of physicians will do this, but the oncologists will be looked to as the experts, as cardiologists are today with cardiovascular disease. Today, many oncologists don't yet think of screening or prevention as part of the scope of their field, but they will in the future. And the way to get prepared for that is to take part in the prevention trials and keep up.

Go to:
Peter Greenwald, MD, PhD, is the director of the Division of Cancer Prevention at the National Cancer Institute (NCI). There, he directs basic, clinical, and public health research on cancer prevention, aimed at significantly reducing cancer incidence, morbidity, and mortality. His responsibilities include developing and conducting clinical trials in cancer prevention, focusing on diet and chemoprevention. Greenwald was selected to present the American Cancer Society Lecture and receive the American Cancer Society award at the 2002 ASCO Annual Meeting. Just as one major NCI-sponsored breast cancer prevention trial was completed, the Journal of Oncology Practice spoke with him about how cancer prevention research will change oncology practice.

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