Hormone Therapy in Survivors of Breast Cancer

DOCTOR'S VIEW ARCHIVE

The use of hormone therapy in postmenopausal women with a history of breast cancer is somewhat controversial. The key background issues in this debate are as follows.

First, breast cancer is clearly a hormone-dependent disease. More specifically, it is dependent on the female hormone, estrogen. This means that many breast cancers (specifically, the ones referred to as estrogen receptor or ER positive) have estrogen binders (receptors). Consequently, estrogens can stimulate the growth of these tumors. Men do get breast cancer, but only at 1% the rate of women.

Second, the likelihood of developing breast cancer is related to the duration of estrogen exposure, and particularly to prolonged, unopposed or uninterrupted exposure to estrogens. Accordingly, this relationship between estrogen and breast cancer is seen in data that shows an increased risk of breast cancer in women with an early menarche (onset of menstrual periods), late menopause, late childbearing (first child after age 30), and no childbearing. There is probably a slightly increased risk of breast cancer with the use of hormone therapy in postmenopausal women.

Third, one of the most effective strategies in the management of estrogen receptor (ER) positive breast cancer is the use of anti-estrogens, such as tamoxifen (Nolvadex), or aromatase inhibitors, such as anastrozole (Arimidex). The tamoxifen interferes with the attachment (binding) of estrogen to its receptor in the breast. The anastrozole blocks the production of estrogen in non-ovarian tissues, which become the principal source of estrogen in post-menopausal women. These anti-estrogenic agents have been clearly demonstrated to be effective in the treatment of metastatic (spread beyond the breasts) breast cancer and as additional (adjuvant) treatment of primary (initial) breast cancer.

Most cancer specialists (oncologists) have felt, therefore, that the use of hormone therapy with estrogen-containing substances is absolutely forbidden (contraindicated) in the management of women who have or have had breast cancer. An opposing viewpoint, however, has become somewhat more popular of late. It allows that there might be a role for hormone therapy after menopause in survivors of breast cancer.

It might be assumed (postulated) that in patients who have a low-risk for recurrence of breast cancer, the primary tumor and all microscopic (tiny) metastases have already been eradicated by the primary treatment of that tumor, with or without additional chemotherapy (drugs that kill cancer). Patients who have a low risk for recurrence of breast cancer are identified as those who initially have, among other features, a small primary tumor and no involvement of the lymph nodes . If this assumption is correct, then the additional risk of recurrence imposed by hormone therapy may be relatively small compared to the problems of osteoporosis and the sometimes-severe vaginal dryness and hot flashes experienced by women after breast cancer treatment.

This emerging viewpoint seems reasonable. Moreover, it has led to several small studies of hormone therapy in carefully selected, low-risk (for recurrence) women with a history of breast cancer. So far, the participants in these studies appear not to have an increased recurrence of breast cancer. However, the number of women in these clinical trials is small and the follow-up is relatively short. Furthermore, as just mentioned, the patients were highly selected, both in terms of the patients desiring to resume estrogen therapy and the oncologists agreeing to work with them. In addition, there are other non-hormonal prescription medications available to prevent and treat osteoporosis that would obviate the need for long-term HT with its still unknown cancer recurrence risks. Furthermore, a few recent well-conducted research trials of women with breast cancer have suggested several non-hormonal prescription medications to be effective and safe in suppressing hot flashes.

In conclusion, I think that there are very good theoretical reasons for not administering estrogen therapy in most women with a history of breast cancer. Nevertheless, there are circumstances involving a select population of post-menopausal survivors of breast cancer, as described above, in which estrogen therapy seems reasonable. In other words, I do not view a history of breast cancer as absolutely forbidding (contraindicating) the use of hormone therapy. Rather, I think that, currently, this therapy is often inadvisable but is sometimes permissible. Put another way, a history of breast cancer is a relative contraindication for the use of estrogens. Still, when hormone therapy is to be used after breast cancer in an individual or in a clinical trial, a full and balanced discussion between the patient, her regular physician, and her oncologist of the relative risks and benefits is mandatory, taking into account available alternatives for hot flashes, vaginal dryness, and osteoporosis.

Medical Author: Michael Lill, M.D.
Medical Editor: Leslie J. Schoenfield, M.D., Ph.D.

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