CHICAGOA 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
In addition to use of HRT, well-established modifiable risk
factors for breast cancer include 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
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."
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
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 Studya prospective cohort of 34,393 at-risk postmenopausal
womenshowing 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 alcohol0.7 g/kg of
ethanol. Within this group, the women who were on HRT had a 300% increase in
their serum 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 riskit’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.