Treating premenopausal women diagnosed with early-stage, hormone-receptor-positive breast cancer with tamoxifen plus 2 years of ovarian suppression after surgery offers better disease-free survival than tamoxifen alone, according to a South Korean study.
Disease-free survival is how long a person lives before the cancer comes back, which doctors call recurrence.
The research was published online on Sept. 16, 2019, by the Journal of Clinical Oncology. Read the abstract of “Adding Ovarian Suppression to Tamoxifen for Premenopausal Breast Cancer: A Randomized Phase III Trial.”
Hormonal therapy and ovarian suppression
After surgery, women diagnosed with early-stage, hormone-receptor-positive breast cancer usually take hormonal therapy medicine to reduce the risk of recurrence. Hormonal therapy given after surgery is called adjuvant hormonal therapy.
Hormonal therapy medicines work in two ways:
- by lowering the amount of estrogen in the body
- by blocking the action of estrogen on breast cancer cells
There are several types of hormonal therapy medicines. Tamoxifen, a selective estrogen receptor modulator (SERM), is one of the most well-known. Tamoxifen can be used to treat both premenopausal and postmenopausal women. The aromatase inhibitors:
- Arimidex (chemical name: anastrozole)
- Aromasin (chemical name: exemestane)
- Femara (chemical name: letrozole)
have been shown to be more effective at reducing recurrence risk in postmenopausal women and are now used more often than tamoxifen to treat women who’ve gone through menopause.
In 2014, two studies, the TEXT (Tamoxifen and Exemestane Trial) and the SOFT (Suppression of Ovarian Function Trial) studies, found that the aromatase inhibitor Aromasin along with ovarian suppression reduces recurrence risk more than tamoxifen in premenopausal women diagnosed with early-stage, hormone-receptor-positive, HER2-negative disease. So younger premenopausal women could take Aromasin as their hormonal therapy as long as their ovarian function also was suppressed.
The SOFT study also found that 5 years of tamoxifen plus ovarian suppression offered better disease-free survival than 5 years of tamoxifen alone.
Ovarian function can be suppressed in one of three ways:
- by taking medicine that stops the ovaries from working
- by surgically removing the ovaries
- by treating the ovaries with radiation
The researchers who did this study, called ASTRRA (Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy), wanted to know if stopping ovarian function for only 2 years instead of 5 would still improve disease-free survival compared to tamoxifen alone.
About the study
The ASTRRA study analysis included 1,282 premenopausal South Korean women who were age 45 or younger and had been diagnosed with early-stage, estrogen-receptor-positive breast cancer. All the women had surgery to remove the breast cancer. All the women were treated with chemotherapy, either before surgery or after surgery.
Other characteristics of the breast cancers:
- 55% of the women had node-positive disease, meaning breast cancer was found in the lymph nodes
- 13.8% of the cancers also were HER2-positive
- 57.5% of the women were treated with taxane chemotherapy
The researchers assessed the ovarian function of the women every 6 months for 2 years after they joined the study to see if the women were still premenopausal. If a woman was considered premenopausal at each visit, she was randomly assigned to one of two treatment groups:
- 5 years of tamoxifen alone: 647 women
- 5 years of tamoxifen plus 2 years of ovarian suppression: 635 women
For this study, ovarian suppression was done with a monthly injection of Zoladex (chemical name: goserelin).
Follow-up time was about 5 years, and 5-year disease-free survival rates were:
- 91.1% for women treated with tamoxifen and ovarian suppression
- 87.5% for women treated with tamoxifen alone
This difference was statistically significant, which means that it was likely because of the ovarian suppression and not just because of chance.
So the results of the ASTRRA study were similar to the results of the SOFT study.
Still, a later analysis of the SOFT study found that ovarian suppression plus tamoxifen caused more side effects and sexual problems, including hot flashes and night sweats, than tamoxifen alone. The ASTRRA study did not include information on side effects, which is a little disappointing.
What this means for you
If you’re a premenopausal woman who has been diagnosed with hormone-receptor-positive, early-stage breast cancer and you want to do everything you possibly can to reduce the risk of the cancer coming back, you may want to talk to your doctor about this and other studies showing that ovarian suppression along with either tamoxifen or Aromasin reduces recurrence risk more than tamoxifen alone.
While the side effects of hormonal therapy can be very severe for some women, they’re overshadowed by the reality that hormone-receptor-positive breast cancer can come back. Hormonal therapy after surgery reduces that risk.
If side effects are a major problem for you, talk to your doctor about ways to manage them. Studies have shown that exercise and acupuncture may reduce hormonal therapy side effects. Visit the Breastcancer.org Staying on Track With Treatment pages to learn more about how to ease side effects.
Written by: Jamie DePolo, senior editor
Reviewed by: Brian Wojciechowski, M.D., medical adviser