Obesity May Boost Odds of Aggressive Breast Cancer in Older Women

Mechanisms besides estrogen appear to play a role, researchers say

TUESDAY, March 1, 2011 (HealthDay News) -- Obesity is known to boost the risk of estrogen-fueled breast cancer in women past menopause. Now, new research suggests a link between postmenopausal obesity and an especially aggressive type of breast cancer that doesn't depend on estrogen to grow.

In a new study that looked at body mass index (BMI) -- a measurement that takes into account height and weight -- women with the highest BMIs had a 35 percent increased risk of developing the aggressive cancer known as triple-negative compared to those with the lowest BMIs, said study leader Amanda Phipps, a postdoctoral fellow at the Fred Hutchinson Cancer Research Center in Seattle. They also had a 39 percent higher risk of developing other breast cancers, the researchers found.

Triple-negative breast cancer is marked by a lack of estrogen, progesterone and HER2 protein expression, hence the name. Only about 10 or 20 percent of breast cancers are triple-negative, experts say, but the outlook is poor because of its aggressiveness and the lack of targeted treatments.

"The new part of this is the triple-negative," Phipps said. While the findings call for further study, they already are reason to repeat the message that keeping a healthy weight is crucial with age, she added.

For their study, published March 1 in the journal Cancer Epidemiology, Biomarkers & Prevention, the researchers evaluated data from 155,723 women enrolled in the Women's Health Initiative, a large-scale study of postmenopausal women begun in 1993. The 15-year study looked at cancer, heart disease and osteoporosis.

Participants, aged 50 to 79 years old, reported exercise habits, weight and height, and their BMIs were calculated.

During the study follow-up, which lasted a median 7.9 years, 2,610 women developed estrogen receptor-positive breast cancer, which is fueled by estrogen, and 307 women developed triple-negative cancer.

Women were divided into four groups, from lowest to highest BMIs. Those in the highest group had BMIs of 31 or higher; 30 and above is termed obese.

The association between triple-negative breast cancer and obesity was what scientists call "borderline" statistically significant, but Phipps said that is probably because of the relatively low numbers of cases in the study.

The researchers also found a modest link between greater physical activity and reduced risk of both kinds of breast cancer, suggesting -- but not proving -- that increased exercise might moderate a woman's risk of these cancers, they said.

When evaluating the risks linked with obesity, Phipps and her colleagues accounted for such factors as age, education, income, family history and ethnicity.

The long-known link between obesity and estrogen-positive breast cancers has been attributed to higher exposure to estrogen in fat tissue. After menopause, most of a woman's estrogen comes from fat tissue. "The more fat, the more estrogen exposure," Phipps said.

But triple-negative cancers aren't responsive to hormones, she said. "The fact that we see such a similar association between the two subtypes [and obesity] tells us it may not just be the hormonal effect of the obesity [driving the risk]," Phipps said.

The exact reasons are unknown, but Phipps said obesity increases markers of inflammation and levels of insulin and insulin-like growth factor. "All of those things could contribute to the growth of the breast tumor," she said.

The study "confirms that obesity [and cancer risk] is not just an estrogen problem," said Dr. Joanne Mortimer, director of the women's cancers program at the City of Hope Comprehensive Cancer Center in Duarte, Calif., who reviewed the study but was not involved in it.

"It's not just the problem of the estrogen feeding the cancer cells," she said.

The fat cells may set up an environment conducive to the growth of breast cancer cells, beyond the effect of the estrogen, she noted.

"I think people assume fat is inert," she said. But, researchers are finding that fat cells "do more than take up space," she added.

More information

To learn more about risk factors for breast cancer, including obesity, visit the American Cancer Society.

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