Combination HRT appears to double the breast cancer risk in women who smoke

Sep 28 2005

Older women who have smoked for 11 or more "pack years" - the lifetime equivalent of a pack a day for at least 11 years - face a 30 percent to 40 percent increased risk of developing breast cancer as compared to women who've never smoked, according to new findings from researchers at Fred Hutchinson Cancer Research Center.

What's more, the researchers found that long-term smokers who add combination hormone-replacement therapy (estrogen plus progestin) to the mix increase their odds of getting breast cancer by 110 percent: more than double that of women who've never smoked or taken HRT.

These findings, by Christopher I. Li, M.D., Ph.D., and colleagues, appear online and will be published in the October print edition of Cancer Causes and Control.

While a number of studies have looked at the association between smoking and breast cancer, many have been inconclusive and many have had conflicting results, Li said, largely because of limitations in data collection, such as not taking into account the duration or intensity of smoking or the timing of smoking onset. In addition, few previous studies have focused on older, postmenopausal women who've had a particularly long smoking history.

"Ours is one of the only population-based studies of its kind to focus on the association between smoking and breast-cancer risk in older women between the ages of 65 and 79. Those who did smoke had much longer histories of smoking than women in previous studies, so we were able to look at the effects of long smoking durations on breast-cancer risk," said Li, an assistant member of the Hutchinson Center's Public Health Sciences Division.

This study is the first of its kind to examine a wide variety of smoking parameters, such as how long and how often a woman has smoked, the number of pack years smoked, whether she was a former or recent smoker, her age at smoking onset, and whether she started smoking before her first full-term pregnancy.

"We found a 30 to 40 percent increased risk of breast cancer among women who were current or long-term smokers, women who started smoking at a younger age and also women who started smoking before their first full-term birth," Li said.

The timing of smoking onset, particularly in relation to first pregnancy, may be related to breast-cancer risk because of the known protective effect of pregnancy on breast tissue. "During pregnancy, breast cells undergo a process called differentiation, which makes them less susceptible to carcinogens, whereas breast cells in women who have never given birth are less differentiated and therefore may be more vulnerable to carcinogenic insults from the toxins in cigarettes," Li said.

The population-based case-control study, funded by the National Cancer Institute, involved nearly 2,000 older women in the Seattle-Puget Sound metropolitan area. Half of the women had a history of breast cancer and half served as a healthy control, or comparison, group. Study participants were interviewed in person and were asked about a variety of factors known to influence breast-cancer risk, including hormone and alcohol use, and reproductive and family history. Even after statistically controlling for these factors, smoking emerged as a significant, independent risk factor for breast cancer, Li said.

Perhaps the most surprising finding surrounded the observation that combined hormone therapy appears to significantly increase breast-cancer risk in women who smoke long term (those with a history of 20 or more pack years of smoking).

"We are really not sure what that finding means, because this correlation hasn't been reported in prior studies," Li said. "We only saw the association in smokers who used both estrogen and progestin and not among women who used estrogen alone. We will follow up on this finding in future studies to see if it can be replicated."

Another interesting -- and encouraging -- finding was that once a woman stops smoking, within about 10 years of quitting her risk of breast cancer falls back to that of a never-smoker. This suggests that recency of smoking may be particularly important with respect to breast-cancer risk, Li said.

"We know that smoking is associated with a lot of diseases, from lung cancer to heart disease, but the association with breast cancer is still somewhat controversial," said Li, who is also an assistant professor of epidemiology at the University of Washington School of Public Health and Community Medicine. "Certainly, the association between smoking and breast cancer is nowhere near as strong as the association between smoking and lung cancer, but breast cancer may be another disease to add to the long list of serious health issues related to smoking."