Estrogen-progestin HRT raises breast cancer risk more than estrogen alone

WESTPORT, Jan 26 (Reuters Health) - Current or recent use of estrogen-progestin hormone replacement therapy (HRT) is associated with a greater increased risk of breast cancer than estrogen-only therapy, according to the results of a study appearing in the January 26th issue of The Journal of the American Medical Association.

"It's been unclear and controversial what the effects of progestin are on the breast," the study's first author, Dr. Catherine Schairer of the National Cancer Institute (NCI) in Rockville, Maryland, told Reuters Health in an interview. "This study suggests that estrogen-progestin may increase breast cancer risk beyond that of estrogen alone."

Dr. Schairer and colleagues at the NCI and the University of Massachusetts at Amherst, analyzed follow-up data collected from 1980 to 1995 on 46,355 postmenopausal women in the Breast Cancer Detection Demonstration Project. Within this sample, the researchers compared 2,082 women with breast cancer to women without a breast cancer diagnosis.

After adjusting for age, education, body mass index, history of mammography and age at menopause, the researchers found that, compared with women who had not taken HRT the relative risk of breast cancer was 1.4 in women who took combination HRT either currently or within the previous 4 years. For women who had recently used estrogen-only therapy, the relative risk was 1.2.

Calculating the linear excess risk, "...the RR of breast cancer increased by 0.01 for each year of estrogen-only use and by 0.08 for each year of estrogen-progestin-only use."

Dr. Schairer's team was only able to detect a statistically significant difference between the effects of the two types of HRT among lean women, those with a body mass index of 24.4 kg per meter squared or less. In her comments to Reuters Health, Dr. Schairer said that the sample of women on combination therapy was too small to detect a significant difference in heavier women.

The study is not the final word on the topic of HRT and breast cancer risk, according to Dr. Schairer. "We need to evaluate longer-term use of estrogen in combination with progestin," she said in the interview. "We [also] need to evaluate different regimens--the cyclic regimen versus combined continuous regimen."

Noting that the study indicates that the risk of breast cancer increases with longer use of HRT, Dr. Walter C. Willett, of Harvard School of Public Health in Boston, Massachusetts, and colleagues write in an accompanying editorial, "This has major implications for risk-benefit considerations because the risks of hip fracture and coronary heart disease--primary targets of preventive use of hormone therapy--do not become large until a decade or more after menopause."

"[F]or women with an intact uterus, the risks and benefits of prolonged use of postmenopausal hormones should be reexamined in light of a likely substantial increase in risk of breast cancer with combined therapy," they write.

But Dr. Trudy Bush, an epidemiologist at the University of Maryland School of Medicine in Baltimore, told Reuters Health in an interview, "Women should not be afraid of this report. If they are on HRT, they should continue."

The majority of studies examining hormone therapy have not detected an increased risk of breast cancer, she said. While this study shows a small connection, it is important to look at the big picture, which does not confirm a risk, she added. Noting that nearly 50 years of research has failed to detect a significant increase in the risk of breast cancer among women taking hormone replacement therapy, Dr. Bush said, "It's time to put the baby to bed."

JAMA 2000;283:485-491,534-535.