Side Effects Greater for Some Given Tamoxifen With Ovarian Suppression

A study looking at differences between tamoxifen-only treatment and tamoxifen plus ovarian function suppression, or OFS, in certain premenopausal women with early-stage breast cancer, found the OFS group experienced more difficulty with menopausal symptoms and other side effects.

Background and Goals

Premenopausal women produce estrogen in their ovaries. In hormone receptor-positive breast cancer, this estrogen fuels the growth of cancer cells. Research has shown that lowering the amount of estrogen in the body can help stop hormone receptor-positive breast cancer from growing.

Chemotherapy may permanently stop the ovarian function that produces estrogen. Premenopausal women with early-stage breast cancer and no cancer in their lymph nodes, known as node-negative disease, might not receive chemotherapy, so their estrogen production continues. (In some cases, women with node-positive disease also might not receive chemotherapy.)

After initial treatment with surgery, these women usually are given tamoxifen, a hormonal therapy, to lower their risk of cancer recurrence, or returning. Tamoxifen blocks estrogen made by the ovaries and, after menopause, made elsewhere in the body. Ovarian function suppression stops the ovaries from producing estrogen.

The researchers were looking to see if there were differences in survival or severity of side effects for women taking tamoxifen alone or in combination with OFS.

Design

The study included only premenopausal women with estrogen receptor-positive or progesterone receptor-positive, node-negative breast cancer. They had early-stage disease, with primary tumors less than 3 cm. The study participants had no chemotherapy.

The women were randomly placed into two treatment groups: tamoxifen alone or tamoxifen plus OFS. Ovarian suppression was achieved either with medicine or by removing the ovaries with surgery.

Treatment was given for 5 years, with yearly monitoring afterwards. Participants answered surveys about side effects.

Results

The study enrolled 345 women, ages 26 to 55, with a median age of 45. Most, 91 percent, were white.

Women receiving tamoxifen plus OFS reported more severe quality-of-life difficulties than did women in the tamoxifen alone group. These problems included

• menopausal symptoms, such as hot flashes
• less sexual activity
• more anxiety and depression

By year 3 of the study, the difference in quality of life between the two groups became statistically significant, or greater than what might happen by chance. That gap shrank over time. The researchers believe this was caused by the tamoxifen-only group reaching menopause and having symptoms like those reported earlier by women in the OFS group.

Limitations

The study ended early because not enough participants were enrolled. This meant the data was not extensive enough to determine how adding OFS to tamoxifen might affect survival. However, results for the women studied suggested no significant difference between the groups for disease-free survival or overall survival. The study size was large enough to reach findings on side effects.

What This Means For You

Although this study did not reach survival findings (see Limitations above), the quality of life results give insight into side effects caused by ovarian suppression. If you are premenopausal, you and your doctor may want to talk about this information along with the results of the much larger SOFT trial, which LBBC reported on a few weeks ago. The SOFT trial determined benefits to using an aromatase inhibitor with ovarian suppression in premenopausal women instead of tamoxifen in combination with OFS, or tamoxifen alone.

What you choose as your hormonal therapy plan may be different from what someone else chooses. You have options, so discuss them fully with your doctor. The best treatment for you will depend upon your diagnosis, other treatments you may have had and personal decisions. The LBBC Helpline can answer your questions about treatment and more.

Tevaarwerk, AJ, Wang, M, Zhao, F, et al.  Phase III Comparison of Tamoxifen Versus Tamoxifen Plus Ovarian Suppression in Premenopausal Women With Node-Negative, Hormone Receptor-Positive Breast Cancer (E-3193, INT-0142): A Trial of the Eastern Cooperative Oncology Group. J Clin Onc. 2014; doi: 10.1200/jco.2014.55.6993.

This article was supported by the Grant or Cooperative Agreement Number 1 U58 DP005403, funded by the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention or the Department of Health and Human Services.