Obesity protects against breast cancer

William J. Cromie:

Being overweight or obese from adolescence to menopause reduces a woman's chances of getting breast cancer, researchers at Harvard Medical School have found. The earlier in life that the researchers looked, the stronger the association, leading to the conclusion that a woman's weight at age 18 is a strong predictor of breast cancer.

In this body size-breast cancer connection, risks are calculated by a height-to-weight comparison known as body mass index, or BMI. Men and women with a BMI lower than 25 are considered normal, as far as their weight is concerned. A BMI between 25 and 30 raises someone to 'overweight status. Higher than 30 earns an 'obese rating. Women with a BMI of 27.5 or higher have 43 percent less chance of getting breast cancer than those who fall between 20 and 22, according to the new study.

To give some idea of the actual sizes involved, a 5-foot, 7-inch woman with a BMI of 20 weighs 127 pounds. BMIs of 25, 27.5, and 30 or more raise weights to 159, 175, and 191-plus pounds.

This finding doesn't mean that it's OK for younger women to binge on french fries and chocolate. Other studies suggest that, for women, the risk of death from all causes increases for every pound of weight above the normal range. Obesity doubles to triples that risk.

Also, protection from breast cancer reverses after menopause. Then, overweight women have a much higher risk for breast cancer than thin women. 'Although a high birth weight is fairly consistently linked to an increase in premenopausal breast cancer, things seem to reverse around puberty, notes Karin B. Michels, an associate professor of obstetrics, gynecology, and reproductive biology who led the study. 'We don't know exactly when the reverse occurs, but then it reverses again after menopause.

So much for health advice. What fascinates Michels and her colleagues at Harvard Medical School and Brigham and Women's Hospital in Boston is the puzzling biology behind the protection. What is responsible for it?

To get an answer, the researchers followed 116,600 registered nurses enrolled in the Brigham and Women's Nurses' Health Study. The women were followed by questionnaires from 1989 until 2003. They were quizzed about their age, weight, height, menstrual cycles, fertility status, family history of breast cancer, use of oral contraceptives, and other factors.

The results turned up two surprises. The first is that BMI at age 18 is a stronger predictor of breast cancer in younger women than their current weight. The next surprise showed that lack of ovulation and irregular menstrual cycles, more common in obese women, apparently do not explain the lower breast cancer risk. That shatters a long-held belief.

The link to age may be partially explained by hormones, the researchers report in the Nov. 27 issue of the Archives of Internal Medicine. Before puberty, females don't have to deal with estradiol (estrogen), progesterone, and other sex hormones involved in ovulation. During their reproductive years, they do. Then things change again after menopause. Between reversals, obese and overweight women have decreased levels of sex hormones, independent of lack of ovulation and irregular menstrual cycles.

Levels of estradiol may be kept low in women with high BMIs for several reasons, including a decreased hormone production capacity or rapid clearance of hormones by the liver or other tissues. Although evidence exists to support the hormone explanation, the mystery is not completely solved. 'Whether decreased estrogen blood levels in premenopausal women explain the protection from breast cancer in obese women remains to be determined, Michels admits.

About 213,000 women will find out they have breast cancer and almost 41,000 will die from it this year, so it's important to learn as much as possible about protection strategies that might somehow be adapted for normal-weight women. Michels has received a new grant from the National Institutes of Health to further probe the perplexing association between weight and breast cancer.

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