Longer HRT Use May Raise Breast Cancer Risk
Study Also Shows Higher Risk for Thinner Women Who Take Hormone Replacement Therapy
By Kathleen Doheny
WebMD Health News
Reviewed By Laura J. Martin, MD
Aug. 10, 2010 -- Hormone replacement therapy (HRT) and breast cancer risk have been long studied, and now a new analysis finds higher risks for normal-weight women and those on combination estrogen/progestin therapy.
While many studies have looked at the link, the new research sheds some new light on the topic, says researcher Tanmai Saxena, an MD/PHD student at the University of Southern California Keck School of Medicine in Los Angeles.
"The study further develops which women are at particular risk with HRT," he tells WebMD. Among his findings: "There is a risk associated with long-term HRT, both estrogen and combination [therapy]. As it turns out, the women who are thinner at menopause when they go on HRT have a higher risk of breast cancer."
The new analysis included 2,857 women participants in the California Teachers Study, all diagnosed with invasive breast cancer and followed on average for about 10 years.
The study is published in Cancer Epidemiology, Biomarkers & Prevention.
HRT and Breast Cancer Risk: Study Details
Saxena and his colleagues looked at the type of hormone therapy used -- estrogen alone or combined with progestin -- and for how long; the researchers took into account the women's body mass index (BMI) and other factors.
When the researchers compared women who had never used hormone therapy to those who reported 15 or more years of estrogen therapy, the estrogen users had a 19% greater breast cancer risk.
Those who used combination therapy for 15 or more years fared worse, with an 83% increased breast cancer risk.
Why so high for the combination therapy? Progestin signals breast tissue to divide, Saxena says, and rapid cell replication boosts the risk of getting cancer.
Body mass index played in to the degree of risk, Saxena found. Women with a BMI of 30 or above, considered obese, did not have an elevated breast cancer risk with increased duration of hormone use, but those with BMI below 29.9 did. However, Saxena points out, obesity alone is a risk factor for breast cancer.
The increased risks found with hormone therapy were confined to specific types of breast cancer tumors -- those positive for both estrogen and progesterone and HER2-positive.
That's bad news tempered with some not so bad, according to Saxena. "If you do get breast cancer from HRT, it tends to be the type more responsive to therapy."
Bottom line of the new analysis? "There are benefits in the relief of menopausal symptoms with hormone therapy, but the risks from hormone therapy are different for different women," Saxena says. "At the end of the day you want to be on hormone therapy for the least amount of time possible and at the lowest dose possible."
While Saxena can't pinpoint a number of years that are "safe," he says that he found elevated risks on combination therapy even for short-term use -- less than five years.
One co-author of the study, Christina A. Clarke, served as an expert witness for plaintiff lawyers pursuing litigation over Prempro hormone therapy.
The new analysis has findings that differ from other clinical trials, such as the Women's Health Initiative (WHI), says Rowan Chlebowski, MD, PhD, a medical oncologist at the LA Biomedical Research Institute in Torrance, Calif., and an investigator for WHI. But that's to be expected, he says, given the design of the two approaches.
The WHI, launched in 1991, included clinical trials and observational studies and tested hormone therapy and other interventions on the risks of heart disease, fractures, and breast and colorectal cancers.
For instance, in the WHI, long-term estrogen-only use, at least initially, reduced the risk of breast cancer, Chlebowski says.
But when it comes to practical decisions, the new analysis, Chlebowski tells WebMD, "probably doesn't change things too much."
For menopausal women, he says, the message is to take hormone therapy if needed to relieve menopausal symptoms for a time. "After a period of time, like a couple of years, reassess," he says.
According to the American Congress of Obstetricians and Gynecologists, a woman should take the smallest dose of hormone therapy that works for her, for the shortest possible time.
"This [finding] doesn't change the message," he says. And that is that the primary reason to take hormone therapy is for relief of menopausal symptoms, not long-term protection from disease.
Rowan Chlebowski, MD, PhD, medical oncologist, LA Biomedical Research Institute, Torrance, Calif.
Tanmai Saxena, MD/PhD student, Keck School of Medicine, University of Southern California, Los Angeles.
Saxena, T. Cancer Epidemiology, Biomarkers & Prevention, Sept. 19, 2010; vol 19.
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