After surgery, women diagnosed with early-stage hormone-receptor-positive breast cancer usually take hormonal therapy medicine to reduce the risk of the cancer coming back (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. In the early 2000s, the aromatase inhibitors:
- Arimidex (chemical name: anastrozole)
- Aromasin (chemical name: exemestane)
- Femara (chemical name: letrozole)
were 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.
Right now, aromatase inhibitors aren’t commonly used to reduce recurrence risk in premenopausal women. But because they’re so much more effective in postmenopausal women, researchers wondered if there were a way to successfully treat premenopausal women with an aromatase inhibitor.
The combined results of two studies suggest that the aromatase inhibitor Aromasin on top of ovarian suppression reduces recurrence risk more than tamoxifen in premenopausal women.
The studies were presented on June 1, 2014 at the 2014 American Society of Clinical Oncology Annual Meeting and published online on the same day by the New England Journal of Medicine.
- Read the ASCO abstract of “Randomized comparison of adjuvant aromatase inhibitor (AI) exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC): Joint analysis of IBCSG TEXT and SOFT trials.”
- Read the NEJM abstract of “Adjuvant Exemestane with Ovarian Supression in Premenopausal Breast Cancer.”
Both the TEXT (Tamoxifen and Exemestane Trial) and the SOFT (Suppression of Ovarian Function Trial) studies wanted to know if aromatase inhibitors could reduce the risk of recurrence in premenopausal women who were diagnosed with early-stage, hormone-receptor-positive breast cancer.
In the TEXT study, Trelstar (chemical name: triptorelin) was used to suppress the ovaries. The women were randomly assigned to receive either:
- Aromasin plus Trelstar for 5 years
- tamoxifen plus Trelstar for 5 years
In the SOFT study, the women were randomly assigned to receive one of three treatments:
- tamoxifen for 5 years
- tamoxifen for 5 years plus ovarian suppression with either 5 years of Trelstar, surgical removal of the ovaries, or ovarian radiation
- Aromasin for 5 years plus ovarian suppression with either 5 years of Trelstar, surgical removal of the ovaries, or ovarian radiation
The SOFT study included a group of women who got only tamoxifen because many doctors suspect that suppressing the ovaries makes tamoxifen more effective. So the SOFT study will allow researchers to see if there is a difference in recurrence rates between women who got only tamoxifen and women who got tamoxifen with ovarian suppression. The results of that analysis are expected later in 2014.
Together, there were 4,690 women in the TEXT and SOFT studies.
After about 5 years, the combined results from the studies showed that compared to women being treated with tamoxifen on top of ovarian suppression, women who were being treated with Aromasin on top of ovarian suppression:
- had a 34% lower risk of recurrence
- had a 22% lower risk of distant recurrence (the cancer coming back in a part of the body away from the breast, such as the bones or liver)
There were similar overall survival rates among women who were treated with Aromasin on top of ovarian suppression and women who were treated with tamoxifen on top of ovarian suppression – about 96% for both groups after 5 years. Overall survival is how long the women lived, whether or not the cancer came back.
Both tamoxifen and aromatase inhibitors can cause side effects. Tamoxifen may cause hot flashes and increase the risk of blood clots and stroke. Aromatase inhibitors may cause muscle and joint aches and pains, as well as hot flashes. Less common but more severe side effects of aromatase inhibitors are heart problems, osteoporosis, and broken bones.
About 30% of the women in both groups reported severe side effects. Women who were taking Aromasin were slightly more likely to withdraw from the studies because of side effects:
- 16% of women taking Aromasin withdrew
- 11% of women taking tamoxifen withdrew
While the results of these studies are promising, they are early results. More analyses will be done, especially on the quality of life of women undergoing ovarian suppression.
“The key question is whether ovarian suppression is really necessary and worthwhile,” said Patricia Ganz, M.D., director of the Division of Cancer Prevention and Control Research at the Jonsson Comprehensive Cancer Center at UCLA and member of the Breastcancer.org Professional Advisory Board. “While it’s a potential advance, the quality of life data are going to be important.
“Ovarian suppression is already bad for quality of life and symptoms, and an aromatase inhibitor makes it worse,” she continued. “Even in postmenopausal women, only about 60% stick it out for 5 years of hormonal therapy. Women would have to individually weigh whether to accept early menopause for a few absolute percentage points in survival. One option may be that if it doesn’t agree with a woman, it can be stopped.”
Larry Norton, M.D., medical director of the Evelyn H. Lauder Breast Center at Memorial Sloan-Kettering Cancer Center and another Breastcancer.org Professional Advisory Board member, said in an interview that ovarian suppression plus Aromasin offers women another treatment option.
“There are reasons why someone might not want to take tamoxifen, just as there are reasons why somebody might want to take tamoxifen. Those are going to enable individualized decisions.”
If you’re a premenopausal woman diagnosed with early-stage hormone-receptor-positive breast cancer and having troublesome side effects from taking tamoxifen after surgery, you may want to talk to your doctor about this study.
If you’re willing to take medicine to suppress your ovaries, you may be able to switch to Aromasin instead of tamoxifen to complete your hormonal therapy treatment.
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.
And stay tuned to Breastcancer.org Research News for the latest updates on the TEXT and SOFT trials.