Hormone Replacement Therapy & the Breast Cancer Link

Hormone replacement therapy (HRT), commonly known as hormone therapy, has been widely used to ease the symptoms of menopause by artificially boosting hormones in the body. However, hormone replacement therapy has also been linked to an increased incidence of breast cancer. Should hormone replacement therapy be used after menopause to increase comfort and quality of life?

Research Shows No Significant Risk

Most studies on the risk of breast cancer in hormone replacement therapy users have found no statistically significant or clinically relevant increase in breast cancer risk when dose is increased, when estrogen is used for up to 20 years, or in those who have a family history of breast cancer or a personal history of benign breast disease compared to nonusers with similar risk factors. When hormone use stops, studies generally find no decrease in breast cancer risk, as would be expected with a causative agent. In a number of studies, women who were hormone replacement therapy users at the time of their breast cancer diagnosis, and who were therefore using hormones while their breast cancer was present, were found to have a more favorable prognosis than nonusers diagnosed with breast cancer. Users' breast cancers do not differ significantly in size and differentiations from those of nonusers.

A study published in the New England Journal of Medicine contained reassuring findings about the use of hormone replacement therapy and breast cancer risk. Current hormone replacement therapy users were less likely to die of breast cancer (relative risk = 0.8) and statistically less likely to die of cardiovascular disease (relative risk = 0.5) (see Table 1). With ten or more years of hormone replacement therapy use, risk of death was significantly less than that of never users (see Table 2). When hormone replacement therapy use was discontinued, risk of death increased (see Table 3).

Table 1. Current* Hormone Replacement Therapy Use & Risk of Death

*No effects found in past users compared to never users
+Compared to never users
#Significant
Grodstein et al. 1997

Table 2. Duration of Hormone Replacement Therapy Use & Risk of Death

*Current users
+Compared to never users
#Significant
Grodstein et al. 1997

Strangely, the study itself and various reports on the study failed to make these reassuring findings clear. Instead, the study pointed to an increase in death rate among longer-term hormone replacement therapy users—an increase from 0.6 to 0.8. With only 163 women with breast cancer in one group and 181 in another, the difference between a relative risk of 0.6 and 0.8 may well be due to chance fluctuations. Even if chance were excluded, long-term hormone replacement therapy users still have a risk of death that is less than that of nonusers (see Table 4).

The authors of the above study cite a previous study that found a “43% increase in death due to breast cancer,” and appear to conclude that the 0.6–0.8 change in the death rate in the 1997 study among longer-term users of hormone replacement therapy is due to breast cancer. Inspection of the earlier study reveals that the 1.43 relative risk to current users was barely statistically significant, with a wider confidence interval than other subgroups, suggesting a smaller sample size that is more subject to random fluctuation. This relative risk was not adjusted for age or seven additional variables used in reporting other risks in the same study, casting further doubt on its validity. Finally, in this study, no increase in breast cancer death rates to past hormone replacement therapy users was present, a finding that is in agreement with at least four other studies that also find no increase in breast cancer death rates among hormone replacement therapy users.

In summary, most studies find that hormone replacement therapy use is not associated with a statistically significant or clinically relevant increase in risk of death due to breast cancer or to an increased incidence of this disease.

Table 3. Years Since Last Use of Hormone Replacement Therapy & Risk of Death

*Compared to never users
+Significant
Grodstein et al. 1997

Editor’s Note: This article has been adapted for Gilbert Guide and abstracted with permission from “Hereditary Breast Cancer Risk: Assessment Is the Easy Part” by Patricia T. Kelly, PhD, Catholic Healthcare West, Bay Area Region, San Francisco, CA, The Breast Journal, Volume 5, Number 1, 1999 52-58. First published on the Cancer Survivor Network, August 28, 2001; updated August 19, 2007.

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