HRT Doubles Breast Density, Abnormal Mammogram Possible

< October 20, 2004 > -- Hormone replacement therapy (HRT) increases breast density and makes breast cancer harder to detect, according to a study presented at a recent meeting of the American Association for Cancer Research.

Over the past few years, several studies have strongly suggested that HRT raises a woman's risk of developing breast cancer.

In July 2002, researchers participating in the Women's Health Initiative (WHI) study found that combined HRT (estrogen plus progestin) increased the risk of breast cancer and cardiovascular events.

The latest research, also from the WHI, finds that combined HRT can double breast density, a known risk factor for breast cancer, and lead to a fourfold increase in abnormal mammograms.

More Difficult To See Abnormalities

The new findings are taken from data collected on 413 postmenopausal women, ages 50 to 79. These women participated in the WHI estrogen-plus-progestin trial, which included more than 16,500 women.

In this study, the women were randomly assigned to receive estrogen plus progestin or a placebo (inactive substance). The women were all given a mammogram at the start of the study and again two years later.

The researchers measured breast density using a computer-aided method that calculates the amount of dense, or white-appearing, tissue on mammography images.

"I was surprised by the magnitude of the effect - the doubling of breast density associated with combination hormone therapy," says lead researcher Dr. Anne McTiernan, the director of the Cancer Prevention Research Program at the Fred Hutchinson Cancer Research Center in Seattle.

"Postmenopausal women who take combination estrogen-plus-progestin hormone replacement therapy for one year experience a twofold increase in breast density and a quadrupled risk of having an abnormal mammogram," Dr. McTiernan says.

This is one more reason for women to reconsider taking hormone therapy and to avoid hormone therapy if they are really concerned about mammograms being the best they can be for diagnosing breast cancer, explains Dr. McTiernan.

Greater Risk for Breast Cancer

Dr. McTiernan notes that the density of breast tissue can increase the risk of breast cancer and also make it more difficult to diagnose.

Since cancer also appears white on a mammogram, increased breast density can make it harder to see tumors and other abnormalities.

"Increased breast density decreases the ability of radiologists to detect breast cancers," she says. "Increased density is also associated with increased risk for breast cancer."

Earlier research conducted by researchers at Fred Hutchinson found that women under age 50 with dense breasts are four times more likely to develop breast cancer compared with similar women who have little or no breast density.

Dr. McTiernan's team says that dense breast tissue "appears to be more biologically active and susceptible to malignancy."

While breast density is largely a function of age and genetics, Dr. McTiernan's study shows that other factors can play a role.

"For several reasons, women should limit the amount of time they are on HRT," she says. "If they are concerned about their risk of breast cancer, they might want to avoid HRT."

New Studies Look for More Clues

Her group is now looking at the effect of estrogen alone on risk of mammogram density.

"We and others are also looking at the effects of other medications or lifestyle factors on mammogram density to see if we can find ways to lower density," she says.

"This is important for women of all ages, but especially for premenopausal women who tend to have high density breasts, which translates into lower effectiveness of mammogram screening for them," she stresses.

"The word is already out that HRT raises breast cancer risk somewhat, and that HRT overall is not useful for disease prevention," says Dr. David L. Katz, director of the Prevention Research Center at the Yale University School of Medicine.

Since HRT for postmenopausal women tends to be used for the treatment of symptoms only, there is nothing in this study that calls for a change in clinical practice, he says.

"If more postmenopausal women are free of HRT, the interpretability of mammograms in this population may improve," Dr. Katz says. "If radiologists cannot interpret mammograms reliably, breast cancer may be over-diagnosed, leading to unnecessary biopsies, or, more importantly, missed tumors.

"Better interpretation of mammograms could in turn mean more detection of early stage breast cancers, and fewer false positive readings," he says.

"We have known for some time that HRT increases breast density in some women," says Dr. Robert Smith, director of cancer screening at the American Cancer Society.

Because increased density makes mammograms more difficult to read, radiologists may see this increased density as something they need to worry about, Dr. Smith says, because it "does increase the risk of a false-positive."

In another report from the same meeting, Dr. Erin Aiello from the Group Health Cooperative's Center for Health Studies in Seattle looked at whether all HRT increased breast density.

Among 46,436 women, they found that all types of HRT increased breast density. Women taking estrogen only had a smaller increase in breast density compared with women taking combined HRT, Dr. Aiello says.

Dr. Aiello notes that breast density usually decreases with age. However, in this study her team found that HRT negated this natural process. "When women stop HRT, breast density decreases," she says.

Always consult your physician for more information.

Online Resources

American Cancer Society

Centers for Disease Control and Prevention (CDC)

National Institutes of Health (NIH)

National Library of Medicine

Susan G. Komen Breast Cancer Foundation

Find a Physician at
St. John's Mercy or call our Physician Referral Service at 314-FOR-DOCS.  

For more information on mammography, please visit health information modules on this Web site.

WHI Postmenopausal Hormone Therapy Trials

The Women's Health Initiative (WHI) was launched in 1991 and consists of a set of clinical trials and an observational study, which together involve more than 161,000 generally healthy postmenopausal women.

The clinical trials were designed to test the effects of postmenopausal hormone therapy, diet modification, and calcium and vitamin D supplements on heart disease, fractures, and breast and colorectal cancer.

The hormone trial had two studies: the estrogen-plus-progestin study of women with a uterus and the estrogen-alone study of women without a uterus.

Women with a uterus were given progestin in combination with estrogen, a practice known to prevent endometrial cancer.

In both hormone therapy studies, women were randomly assigned to either the hormone medication being studied or to placebo. Those studies have now ended. The women in these studies are now participating in a follow-up phase, which should last until 2007.

The WHI provides results from the first phases of the hormonal therapy studies:

Q. Why were the women in the WHI estrogen-plus-progestin study told to stop study pills in July 2002?

A. When it reviewed the study data in May 2002, the WHI Data and Safety Monitoring Board saw an increased risk of breast cancer in women taking estrogen plus progestin. The Board also saw that the previously identified risks for heart attacks, strokes, and blood clots to the lungs and legs had persisted. Therefore, in the judgment of the Board, the overall risks outweighed the benefits of taking estrogen plus progestin.

Q. What were the main findings in the WHI study on estrogen-plus-progestin?

A. The main findings show that compared to women taking placebo pills:

• The number of women who developed breast cancer was higher in women taking estrogen plus progestin.
  
  
• The numbers of women who developed heart attacks, strokes, or blood clots in the lungs and legs were higher in women taking estrogen plus progestin.
  
  
• The numbers of women who had hip and other fractures or colorectal cancer were lower in women taking estrogen plus progestin.
  
  
• There were no differences in the number of women who had endometrial cancer (cancer of the lining of the uterus) or in the number of deaths.

Q. What are the increased risks for women taking estrogen-plus-progestin?

A. For every 10,000 women taking estrogen plus progestin pills:

• 38 developed breast cancer each year compared to 30 breast cancers for every 10,000 women taking placebo pills each year.
  
  
• 37 had a heart attack compared to 30 out of every 10,000 women taking placebo pills.
  
  
• 29 had a stroke each year, compared to 21 out of every 10,000 women taking placebo pills.
  
  
• 34 had blood clots in the lungs or legs, compared to 16 women out of every 10,000 women taking placebo pills.
  

Q. What are the reduced risks for women taking estrogen-plus-progestin?

A. For every 10,000 women taking estrogen plus progestin pills:

• 10 had a hip fracture each year, compared to 15 out of every 10,000 women taking placebo pills each year.
  
  
• 10 developed colon cancer each year, compared to 16 out of every 10,000 women taking placebo pills. 
   

Q. What are the conclusions from these findings?

A. The main conclusions are:

• The estrogen plus progestin combination studied in WHI does not prevent heart disease.
  
  
• For women taking this estrogen plus progestin combination, the risks (increased breast cancer, heart attacks, strokes, and blood clots in the lungs and legs) outweigh the benefits (fewer hip fractures and colon cancers). 

Always consult your physician for more information.