CHICAGO—A large body of epidemiological literature has identified a number of breast cancer risk factors that are not considered modifiable, Susan Gapstur, PhD, said at the Fifth Annual Lynn Sage Breast Cancer Symposium. These include family history of breast cancer, age, personal history of atypia, hormone levels and hormonally related factors such as dense breasts, age of first childbearing, and age at menopause.
"Aside from long-term use of combined hormone replacement therapy (HRT), our most well-confirmed risk factors for breast cancer are largely not modifiable," said Dr. Gapstur, associate professor of preventive medicine, program leader in cancer prevention, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University.
In addition to use of HRT, well-established modifiable risk factors for breast cancer include alcohol(Drug information on alcohol) intake and postmenopausal overweight or obesity, she said.
"There is strong evidence that alcohol intake is associated with the risk of breast cancer. There is also clear evidence that a high body mass index (BMI) or obesity or overweight in postmenopausal women is associated with an increased risk of breast cancer, although in premenopausal women, obesity is related to a reduced risk of breast cancer," Dr. Gapstur said.
She suggested that there may be "a whole combination of lifestyle factors that one needs to consider when thinking about the risk of breast cancer, including physical activity, BMI, and diet."
Alcohol Intake
In 1977, Williams and Horm (J Natl Cancer Inst 58:525-547, 1977) were the first to look for an association between alcohol consumption and risk of breast cancer. According to Dr. Gapstur, this study found that women who consumed above the median level of alcohol intake had approximately a 55% higher risk of breast cancer than nondrinking women. Since then, more than 80 studies have been published on alcohol consumption and breast cancer risk.
One study pooled data from six large cohort studies and found a clear dose-response relationship up to the very highest level of consumption: There was a 9% increased risk of breast cancer with each increase of 10 g (about one drink) per day in ethanol consumption. These results were confirmed by an analysis that combined data from 53 large epidemiologic studies.
According to Dr. Gapstur, studies have shown that the increased breast cancer risk does not differ according to the type of alcoholic beverage that is consumed, and both pre- and postmenopausal women have a similar increase in risk due to higher alcohol consumption.
She also pointed out that there is little association between alcohol consumption during early adulthood and increased breast cancer risk. "Most of the risk has been associated with recent adult drinking (near the time of breast cancer diagnosis). And that might point to a potentially important mechanism: Alcohol may have promoting effects once the tumor has been initiated," she said.
Certain groups may be at higher risk from alcohol consumption as a result of other lifestyle factors or genetic susceptibility. "My colleagues at Georgetown University have developed a model for studying the mechanism between alcohol and breast cancer risk," she said. "They are exploring several different pathways: One is that ethanol could affect estrogen metabolism, which could lead to aberrant cell responses and proliferation. Alternatively, it could have effects on DNA damage. Finally, there may be dietary and genetic factors that interact with alcohol to increase breast cancer risk."
A decade ago Dr. Gapstur published an analysis from the Iowa Women’s Health Study—a prospective cohort of 34,393 at-risk postmenopausal women—showing an increasing risk of breast cancer with increasing alcohol consumption in women who had ever used hormone therapy.
Dr. Gapstur explained, "There is some evidence that alcohol’s mechanism may be through hormone metabolism. In a 1996 study, postmenopausal women received a single acute dose of alcohol—0.7 g/kg of ethanol. Within this group, the women who were on HRT had a 300% increase in their serum estradiol(Drug information on estradiol) levels."
Based on information derived from the National Health and Nutrition Examination Survey, the amount of breast cancer that could potentially be attributed to alcohol consumption is 2% to 4% of US breast cancer cases, or about 4,200 to 8,400 cases annually. "Reducing alcohol consumption is something that a woman can do to alter her risk—it’s a modifiable lifestyle factor," she said.
Dr. Gapstur noted that the interest in the relationship between diet and breast cancer risk factors focuses on cross-cultural comparisons that have found a 40- to 50-fold difference in breast cancer incidence rates across different cultures.
