Is Hormone Replacement Safe After Breast Cancer? Maybe Not.

Arguments have persisted for many years regarding the safety of using hormone replacement during or after the treatment for early-stage (stage I or II) breast cancer. Several clinical trials suggested that post-treatment hormone therapy increased the risk of breast cancer recurrence whereas others did not see any adverse impact. To make things more confusing, there are two types of hormone replacement. One is systemic therapy with patches injections or pills (systemic therapy), and the other is using vaginal tablets or suppositories (vaginal therapy) for replacement needs. In fact, a large analysis of many studies from the Collaborative Group on Hormone Factors in Breast Cancer noted an increase in the risk of new primary cancers in women who have never had breast cancer treated with systemic hormones but not with vaginal hormones. This most recent study published by Cold et.al., published in the Journal of the National Cancer Institute studied a very large group of Danish postmenopausal women with estrogen receptor-positive breast cancer. All patients in this study received five years of tamoxifen, an aromatase inhibitor (anastrozole, letrozole, exemestane), or both in sequence, or received no hormone therapy.

From 1997-2004, 9710 postmenopausal women had surgery for estrogen receptor-positive breast cancer. Some of these patients who had previously been prescribed hormones were eliminated from the study. Of the remaining 8461 patients, 1957 were prescribed vaginal estrogens, and 133 were prescribed systemic hormones with or without vaginal estrogen. The average time of follow-up for this group of patients was 9.8 years.

The initiation of hormone therapy initiated during adjuvant treatment with aromatase inhibitors

The rate of recurrence of breast cancer in women receiving vaginal hormones was very similar to women who had never used hormones. However, when the researchers examined specifically the group of women who used vaginal hormone replacement initiated when patients were receiving an aromatase inhibitor for their breast cancer, they noted that this group had an increased risk of recurrence (39% increase). This was not the case for women who received systemic hormones and aromatase inhibitors where no increase was seen in the risk of breast cancer recurrence. As opposed to an aromatase inhibitor the same risk increase was not seen in those women treated with tamoxifen. As opposed to recurrence of disease, the overall survival of patients was not affected by using either vaginal or systemic hormones when compared to never-users.

Based on prior studies it is been observed that serum estrogen levels are elevated within the first three months after initiating vaginal hormones. Aromatase inhibitors lower or nearly eliminate estrogen. The authors of this article suggest that even a modest increase in circulating estrogens may have contributed to the observed increase in the risk of recurrence in this subgroup. Tamoxifen does not work the same as aromatase inhibitors. Tamoxifen blocks what is called the estrogen receptor and even slight elevations in estrogen levels seen on tamoxifen treatment are counteracted by this blockade of the receptor. Aromatase inhibitors do not block the estrogen receptor but block the conversion of cortisone to estrogen in peripheral tissues such as the liver and fat. Therefore, aromatase inhibitors do not block the small increases seen in estrogen when women or prescribed vaginal estrogen replacement.

Conclusion

In this group of postmenopausal, estrogen receptor-positive breast cancer patients, no decrease in survival or recurrence was seen in those women taking either systemic or vaginal hormone replacement. However, and one subset of patients, those taking aromatase inhibitors, vaginal but not systemic estrogen therapy was noted to increase the recurrence rate of breast cancer. The authors of the study suggest that for early-stage breast cancer patients receiving adjuvant aromatase inhibitors, vaginal estrogen therapy should be used with caution.

Dr. Alan Stolier, MD, FACS, clinical breast oncologist, shares his expert medical perspective with a series of educational and scientific articles.