Hormone Replacement Therapy and Mammogram Accuracy

Reprinted with kind permission of Johns Hopkins Breast Center magazine, Artemis

A report just published in the Journal of the American Medical Association confirmed previous studies which found that women who take hormone replacement therapy (HRT) may develop denser breast tissue, which in turn may make it more difficult to detect breast cancer through mammography.

However, the researchers, led by Dr. Stephen Taplin of the Group Health Cooperative of Puget Sound, Seattle, also found that this effect was temporary. Breast density returned to normal once hormone therapy was discontinued.

A woman’s use of hormone replacement therapy is important to monitor, they said, because increased breast density impairs the accuracy of screening mammography and is a strong risk factor for missing cancer.

They cautioned that their findings do not suggest that women change their hormone use. Rather, their study should discourage women from stopping and starting hormone treatment in order to decrease their breast density, they said.

A Primer on HRT

Hormone replacement therapy-often referred to as HRT-is used to replace hormones not being produced after menopause. It can significantly reduce a woman’s risk of osteoporosis and heart disease. While developing breast cancer is a top concern among many women, more than 10 times as many women actually die from cardiovascular disease.

And yet, exposure to hormones is thought to increase a woman’s risk of developing breast cancer. Since HRT adds estrogen (and often progesterone) back to the body, many studies have looked for a possible link between the use of HRT and breast cancer.

Although it still has not been proven that estrogen causes breast cancer, estrogen may help some breast cancer cells grow when the tumor is already present in a woman’s body. Therefore, once a woman is diagnosed with breast cancer, tests are done to see if her cancer is positive for estrogen and progesterone receptors. These receptors are the parts of a cancer cell that attract estrogen or progesterone.

If the cancer is found to have these receptors, hormones flowing in the body can attach themselves to breast cancer cells and help those cells grow and multiply. In these cases, therapies such as tamoxifen are used to prevent hormones from attaching to the cancer cells.

Women need to consider their personal risks for osteoporosis and heart disease, in addition to their personal risk for breast cancer, when making decisions about hormone replacement therapy.

For an average women at low risk for breast cancer, or one who is at an increased risk for cardiovascular disease or osteoporosis, the small increased risk of breast cancer associated with long-term hormone replacement therapy may be worth it to her.

Conversely, for some women at an increased risk for breast cancer due to advancing age, a strong family history, or premalignant biopsies, the risks of hormone replacement therapy may outweigh the benefits.

Dense Breast Tissue

Approximately two-thirds of premenopausal women have dense breasts. In postmenopausal women, about one-quarter have dense breasts, and the rate increases to about half of postmenopausal women who take hormones. Breast density is the most significant factor in predicting the sensitivity-and thus accuracy-of a mammogram. As the density of breast tissue increases, the sensitivity of a mammogram decreases.

A major study last year by a group of radiologists in New York City, led by Dr. Thomas Kolb, found that a combination of mammography and ultrasound can provide dramatic improvements in detecting breast cancers in women with dense breast tissue. They based their conclusion on a review of more than 18,000 breast cancer screenings using mammography, ultrasound and physical clinical exams, either alone or in combination.

Breast ultrasound involves sending high-frequency sound waves through the breast, which are then picked up and translated by a computer into an image that is displayed on a screen. Ultrasound can detect the increased blood flow common to cancers and can distinguish between cancerous and noncancerous cysts. It can also be used to help doctors precisely guide a biopsy needle into breast lesions.

Kolb explained that ultrasound is more effective than mammography in detecting cancer in women with dense breasts because of its ability to "contrast" breast tissue. In ultrasound, dense breast tissue appears white, while the cancer is dark. Conversely, in a mammographic image, both the dense breast tissue and the cancer are white, making it more difficult to distinguish between the two.

However, ultrasound’s use as a regular screening tool for most women is not recommended because small calcium deposits, which are one of the earliest signs of breast cancer, are not visible by ultrasound.

Risk of False-Positive Mammograms

According to a report published in the Journal of the National Cancer Institute, almost a quarter of all women who regularly underwent screening mammograms over a 10-year period received a false-positive result from at least one of their exams. One of the prime risk factors-estrogen in hormone replacement therapy.

A false-positive result from a mammogram means that additional testing after an abnormal result found that a woman did not actually have cancer. More specifically, it means that no cancer was diagnosed within one year after the abnormal exam.

Dr. Cindy Christiansen of Boston University and colleagues reviewed the medical records of 2,227 women who received between one and nine mammograms over the ten-year study period. They found that 6.5 percent of the total of 9,747 mammograms were false-positive. However, eventually 23.8 percent of the women had at least one false-positive result because of undergoing multiple screenings.

Importantly, the researchers found that the risk of a false-positive mammogram increases with current or past use of estrogen. In fact, they noted that women currently using estrogen had about a 29 percent increased risk of getting a false-positive result.

Other factors affecting mammogram accuracy included the number of breast biopsies performed, family history of breast cancer, relative youth, and length of time between mammograms.

References:

Sources:

Journal of the American Medical Association, January 10, 2001; 285:171-176

American Journal of Epidemiology, November 2000; 152:950-964

Cancer, June 2000; 88:2561-2577

Journal of the National Cancer Institute, February 16, 2000; 92:328-332

American Association of Clinical Endocrinologists ()

The Susan. G. Komen Breast Cancer Foundation (http://www.komen.org)

American Institute of Ultrasound in Medicine (http://www.aium.org)