Women under age 45 have another good reason to shed surplus pounds: Obesity can significantly decrease their ability to survive breast cancer.
A Hutch study led by the Public Health Sciences Division's Dr. Janet Daling and published yesterday in Cancer found that young women with breast cancer who are overweight are more than two times as likely to die of the disease than their thinner counterparts.
What's more, breast tumors from heavier women tend to be larger and to have molecular characteristics indicative of aggressive cell growth.
"Most studies of obesity and breast cancer prognosis have focused on older - postmenopausal - women and have shown that heavier women have a higher risk of mortality," Daling said. "This is one of the few studies to look at younger or largely premenopausal women."
More aggressive treatment
The findings may be useful to physicians evaluating breast-cancer prognosis and suggests that more aggressive treatment may be warranted for overweight patients.
Funded by the National Cancer Institute, the study also involved Dr. Kathi Malone, David Doody and Lisa Johnson of PHS, Dr. Julie Gralow of the University of Washington Department of Oncology and Dr. Peggy Porter of the Human Biology and PHS divisions.
The team conducted a population-based study to track survival among 1,177 western Washington women under age 45 who were diagnosed with invasive ductal breast cancer between 1983 and 1992.
Two previous studies
The women had been interviewed in two previous studies about their body-size history, including adult height and weight one year prior to diagnosis, maximum lifetime weight and weight at age 18. The information was used to calculate body mass index (BMI), a measurement of weight relative to height that often is used as a marker of obesity.
Study participants were classified into quartiles (fourths) of BMI. The highest quartile included women who would be considered overweight.
The researchers identified patient deaths using information from the Hutch's Cancer Surveillance System, a population-based cancer registry that is part of the National Cancer Institute's Surveillance, Epidemiology and End Results program, as well as through contact with the families of the women.
Women in the highest BMI quartile had more than two times the risk of dying of their diseaseduring the five years after diagnosis compared to women in the lowest quartile of body weight. At 10 years, 34 percent of women in the highest quartile had died, compared to 21 percent of women in the lowest quartile.
A striking characteristic of tumors of women in the highest BMI quartile was that more than two-thirds were larger than 2 centimeters in size, while only half of the women in the lowest quartile had tumors that large.
Daling said it is unlikely that decreases in detection or differences in tendency to seek medical care account for the disparity of tumor size between the two weight groups.
"The proportion of women who had mammograms was virtually identical in each quartile," she said. "I think the reason heavier women have larger tumors is that they are faster-growing than those found in thinner women."
To test that, characteristics of the large tumors from the heaviest women were compared with those from the thinnest women.
Indeed, a molecular analysis led by Porter revealed that the tumors from heavier women were more likely to have positive markers indicative of high levels of cell division.
The effects of obesity on breast-cancer mortality may have important clinical implications, Daling said.
"Overweight women may need to be treated for their cancers more aggressively," she said. "It might mean they should be treated with chemotherapy after surgery even if their cancers haven't apparently spread to the lymph nodes."
What's making the tumors in heavy women grow faster is unclear, Daling said, but it's unlikely to be due to estrogen levels, as is the case with postmenopausal women.
"In postmenopausal women, there is little endogenous estrogen, and the relation of high BMI to mortality may be due to the production of estrogen in fat cells," she said. "But in premenopausal women, regardless of their BMI, ovarian-derived estrogen levels are high and outweigh any contribution of estrogen produced by fat cells."
To identify factors that may influence tumor growth in relation to BMI, Johnson will analyze blood samples from the study participants collected during the initial interviews.
Levels of insulin and leptin (a protein produced by fat cells) are known to be related to BMI. Johnson's study will investigate how these metabolic hormones relate to tumor characteristics and will hopefully shed light on the biologic mechanisms underlying the increased mortality seen in obese breast-cancer patients.