The hidden fat factor in older women

Even moderate physical activity can reduce cancer, heart disease, diabetes risk in those past menopause

Getting regular, moderate-intensity exercise may be critically important for postmenopausal women who want to reduce their risk of cancer, heart disease and other chronic diseases.

The reason: Exercise effectively reduces intra-abdominal fat, a hidden risk factor for many chronic illnesses.

Dr. Anne McTiernan and colleagues based their conclusions on the largest randomized clinical trial to assess the effect of exercise on overall and intra-abdominal obesity in postmenopausal women.

"Even if a woman who exercises regularly doesn't see the benefits of dramatic weight loss on her scale, our results indicate that she can feel confident that she is improving her health," McTiernan said. "Regardless of the amount of weight lost, we now know that exercise reduces hidden intra-abdominal fat, the most dangerous type of fat."

Reducing intra-abdominal, or visceral, fat is important because in addition to increasing the risk of cardiovascular disease and diabetes and other conditions, such fat can raise insulin levels, which promotes the growth of cancer cells.

People with high levels of intra-abdominal fat may not even know it because it is hidden, deposited around the internal organs within the abdomen, McTiernan said.

The year-long study involved more than 170 previously sedentary, overweight, postmenopausal Seattle-area women. None took hormone-replacement therapy. Half were randomly assigned to a moderate-intensity, aerobic-exercise group, and half, who served as a comparison group, attended a weekly hour-long stretching class.

Those in the exercise group, who worked out at home and at a gym for at least 45 minutes five days a week - an amount similar to current national recommendations - achieved significant reductions in weight, total body fat and intra-abdominal fat.

After a year on the program, while the amount of body weight lost was modest yet statistically significant, the exercisers lost between 4.3 percent and 7.4 percent intra-abdominal fat while maintaining their calorie intake.

Women who had the highest adherence to the program experienced the largest decreases in weight, total fat and intra-abdominal fat. The women in the stretching group, in contrast, experienced a slight gain in intra-abdominal fat.

"The beauty of exercise as a method to reduce total and intra-abdominal fat - and therefore chronic disease - is that it can be done by most women at low cost and with low risk of side effects," McTiernan said.

Hormone therapy linked to increase of slower-growing form of breast cancer

Combination hormone-replacement therapy (HRT) made headlines last summer when a landmark study showed that use of the drug boosts a woman's risk of developing breast cancer.

Now, a new study led by Dr. Janet Daling and colleagues reveals that the increased risk is limited to a less aggressive form of the disease known as lobular breast cancer.

The findings help to explain why incidence of this rarer form of breast cancer has increased steadily over the past decade among postmenopausal women in the United States. In contrast, incidence rates for ductal carcinoma, the more common type, have remained steady.

The researchers found that among women under age 65, those who used combination hormone therapy for at least six months had about a two-fold increased risk of developing lobular breast cancer compared to women who did not use such therapy.

Although earlier studies, including ones conducted at Fred Hutchinson, indicated a link between combined HRT use and lobular cancer, Daling said that the scope of the current study substantiates its findings.

Still, she and her collaborators caution that theirs was a case-control study, which relied on a woman's recall of the types of HRT she had used in the past. Researchers generally regard randomized trials, in which study participants are randomly assigned - or not - to a particular course of treatment or intervention, as more definitive analyses.

Although lobular breast cancer is generally less aggressive than ductal breast cancer, Daling said that the jury is still out on whether combination HRT use is linked to increased mortality due to breast cancer.

"This type of cancer does have a 15 to 25 percent lower risk of mortality," she said. "However, this may not result in lower mortality overall since the incidence of lobular cancer appears to be increasing due to use of this drug."

Targeted immune-system cells may destroy melanoma tumors

An experimental cancer therapy that uses immune-system cells to target and destroy tumors shows promise for treating patients with advanced melanoma, a potentially fatal form of skin cancer.

The treatment halted tumor growth in more than half of those who underwent therapy in a Fred Hutchinson study.

During the procedure, patients are infused with their own immune cells, which are triggered to react against melanoma cells. Although not a cure, the technique could provide new options for those who do not achieve a complete response to primary therapy, researchers said.

The work was led by Fred Hutchinson's Dr. Cassian Yee and colleagues at the center, the University of Washington and the Mayo Clinic.

The study was one of the first to apply this type of immunotherapy, known as adoptive T-cell therapy, to a solid tumor and was more comprehensive than prior analyses, Yee said.

In adoptive T-cell therapy, a patient's T cells are extracted, and those that recognize a desired target, such as a protein on the surface of cancer cells, are identified and stimulated to divide. This population of identical cells, or clones, is then infused back into the patient.

Yee's study involved 10 patients with metastatic melanoma who had failed conventional therapy. Disease progression was stabilized in five of the patients and partially stabilized in three other patients for up to 21 months. Typically, patients with such advanced disease have a median survival of four or fewer months.

Although most patients experienced slight fever, aches and pains, no significant toxic side effects were associated with the treatment.

Mysterious protein helps body fight bacterial infection

New research led by Dr. Roland Strong's laboratory sheds light on how the immune system thwarts potentially harmful bacterial infections. Researchers found that a previously mysterious protein called NGAL accomplishes this by robbing bacteria of iron, a nutrient required for their growth.

Strong and graduate student David Goetz discovered that the NGAL protein binds to an iron-scavenging molecule produced by the intestinal bacterium E. coli. They are now investigating whether NGAL can bind to iron-scavenging molecules from other types of disease-causing bacteria with the hope of using it to develop new therapies.

Your Gifts at Work

Wodarz uses math models to study cancer, HIV

Studies of predators and their prey are usually the turf of ecologists. But research on the competition between living things doesn't just take place in the rain forest or savannah. It also takes place at Fred Hutchinson, where Dr. Dominik Wodarz, a mathematical biologist, applies the basic principles of evolution to develop new strategies for treating AIDS and cancer.

Thanks in part to private donations, the center recruited Wodarz last year from the Institute for Advanced Study in Princeton, N.J. There, he and collaborators developed mathematical models to predict drug regimens that would best stimulate the human immune system to win the race against HIV, the virus that causes AIDS. He has also developed mathematical models for studying cancer progression and treatment.

"Many immune-system factors interact during a viral infection or during cancer development," he said. "To understand the outcome, you can't design experiments without mathematical equations."

Wodarz has begun collaborations with Fred Hutchinson laboratory researchers who study the dynamics of HIV infection or tumor progression. "You can learn the most about how to develop disease therapies by a combination of the theoretical and the experimental," he said.

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