Pre-menopausal women diagnosed with early-stage, hormone receptor-positive breast cancer who took an aromatase inhibitor along with ovarian suppression after surgery had a 3.2% lower risk of the cancer coming back (recurrence) than women who took tamoxifen after surgery, according to a study. Still, there was no difference in overall survival.
The research was presented on Dec. 8, 2021, at the San Antonio Breast Cancer Symposium. Read the abstract of “Aromatase inhibitors versus tamoxifen in pre-menopausal women with estrogen receptor positive early stage breast cancer treated with ovarian suppression: A patient level meta-analysis of 7,030 women in four randomised trials.”
Overall survival is how long the women lived, whether or not the cancer came back.
Senior clinical research fellow Jeremy Braybrooke, PhD, and medical statistician Rosie Bradley, from the University of Oxford, recently joined the Breastcancer.org Podcast to discuss the study’s findings.
Hormonal therapy and ovarian suppression
After surgery, women diagnosed with early-stage, hormone receptor-positive breast cancer usually take hormonal therapy medicine — also called endocrine therapy or anti-estrogen therapy — to reduce the risk of recurrence. Doctors call hormonal therapy given after surgery 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. Both pre-menopausal and post-menopausal women can take tamoxifen.
The following aromatase inhibitors have proved to be more effective at reducing recurrence risk in post-menopausal women:
- Arimidex (chemical name: anastrozole)
- Aromasin (chemical name: exemestane)
- Femara (chemical name: letrozole)
Doctors now prescribe these three aromatase inhibitors more often than they prescribe tamoxifen for women who’ve gone through menopause.
In 2014, the TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) studies found that Aromasin along with ovarian suppression reduced recurrence risk more than tamoxifen in pre-menopausal women diagnosed with early-stage, hormone receptor-positive, HER2-negative breast cancer.
The results suggested that doctors could offer pre-menopausal women Aromasin as hormonal therapy after breast cancer surgery as long as they also suppressed ovarian function.
The SOFT study also found that five years of tamoxifen plus ovarian suppression offered better disease-free survival than five years of tamoxifen alone.
Disease-free survival is how long the women lived without the cancer coming back.
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
About the study
This study was a meta-analysis, a study that combines and analyzes the results of a number of earlier studies. In this case, the researchers analyzed four studies comparing an aromatase inhibitor with tamoxifen in pre-menopausal women diagnosed with early-stage, hormone receptor-positive breast cancer:
- the TEXT study, which compared five years of Aromasin with five years of tamoxifen and used Trelstar (chemical name: triptorelin) to stop the ovaries from working
- the SOFT study, which also compared five years of Aromasin with five years of tamoxifen and used Trelstar to stop the ovaries from working
- the HOBOE study, which compared five years of Femara with five years of tamoxifen and used Trelstar to stop the ovaries from working
- the ABCSG12 study, which compared three years of Arimidex with three years of tamoxifen and used Zoladex (chemical name: goserelin) to stop the ovaries from working
Combined, the four studies included 7,030 pre-menopausal women diagnosed with early-stage, hormone receptor-positive breast cancer.
Chemotherapy affects the risk of recurrence. So the researchers noted differences in the number of women who received chemotherapy and the timing of those treatments across all four trials:
- In ABCSG12, chemotherapy was only allowed before surgery; 5% of the women received chemotherapy
- In TEXT, chemotherapy was optional and given at the same time as ovarian suppression; 60% of the women received chemotherapy
- In SOFT, chemotherapy was given before the women were randomly assigned to either the Aromasin or tamoxifen groups, but the women had to still be pre-menopausal after chemotherapy; 54% of the women received chemotherapy
- In HOBOE, chemotherapy was given before the women were randomly assigned to either the Femara or tamoxifen groups; 63% of the women received chemotherapy
Half the women in the studies were followed for less than eight years, and half were followed for a longer time.
Overall, the analysis found that the five-year risk of recurrence was:
- 6.9% for women who took an aromatase inhibitor and had ovarian suppression
- 10.1% for women who took tamoxifen
The researchers pointed out that aromatase inhibitors were more beneficial than tamoxifen in the first four years of treatment — when the hormonal therapy treatment was different. After the women completed hormonal therapy treatment between years five and nine, aromatase inhibitors were not more beneficial or less beneficial than tamoxifen.
The five-year risk of distant recurrence — the cancer coming back in a part of the body away from the breast, such as the bones or liver — also was slightly lower in women who took an aromatase inhibitor. Five-year distant recurrence risk was:
- 10.2% for women who took an aromatase inhibitor and had ovarian suppression
- 12.1% for women who took tamoxifen
Still, there was no difference in the number of women who died from breast cancer between the two treatment groups. But the researchers pointed out that a longer follow-up period is needed to accurately assess any differences.
When the researchers looked at side effects, they found that women who took an aromatase inhibitor had more bone fractures than women who took tamoxifen:
- 5.0% of women who took an aromatase inhibitor and had ovarian suppression broke a bone
- 3.8% of women who took tamoxifen broke a bone
What this means for you
If you’re a pre-menopausal woman diagnosed with early-stage, hormone receptor-positive breast cancer, and are deciding on hormonal therapy treatment after surgery, the results of this study give you a number of things to discuss with your doctor.
“What we know from other analyses is that extending endocrine treatment beyond five years seems to give additional benefit,” Dr. Braybrooke told Breastcancer.org. Dr. Braybrooke, one of the study’s authors, also is a consultant medical oncologist and clinical lead for oncology at University Hospitals Bristol and Weston NHS Foundation Trust. “But of course that then needs to be balanced against [recurrence] risk and side effects.”
Aromatase inhibitors and tamoxifen can cause a number of troubling side effects that can reduce quality of life.
The most common side effects of aromatase inhibitors are:
- joint pain
- hot flashes
- broken bones
The most common side effects of tamoxifen are:
- hot flashes
- loss of libido
Tamoxifen also may cause more serious side effects, including endometrial cancer and blood clots.
Research has shown that about 25% of women who are prescribed an aromatase inhibitor or tamoxifen to reduce the risk of recurrence after surgery either don’t start taking the medicine or stop taking it early, in many cases because of side effects.
“What [recent] studies have shown is that [recurrence] risk does seem to relate to the stage of the cancer at the time of initial diagnosis,” Dr. Braybooke continued. “So even many years later, that risk seems to be greater if you have a bigger tumor, if you have more positive lymph nodes. That’s where it starts to influence our earlier decision-making as to which treatment may be the best for each individual patient.
“I think it’s particularly important for pre-menopausal women [to see] what the effect of ovarian suppression is on them and their day-to-day function,” he added. “Because you’re inducing a rapid, early menopause, often in very young women with a long life expectancy ahead of them. Certainly, as a clinician, I spend a lot of my time having those conversations, trying to balance potentially the most effective treatment with something that’s manageable. And different women will have different perceptions of what’s most important to them. Absolutely we have to consider that as well in those discussions.”
Research has shown that hormone receptor-positive breast cancer can come back 10 to 30 years after diagnosis. So it’s very important that you take hormonal therapy medicine for as long as it’s prescribed and at the prescribed dose.
If you’re having troubling side effects, talk to your doctor right away. Don’t wait until the symptoms are intolerable and you have to stop taking the medicine. There are steps you can take to ease these side effects, including switching to a different type of hormonal therapy.
Read more about Staying on Track With Treatment to learn why it’s so important to stick to your treatment plan, and ways to manage side effects after radiation, chemotherapy, and hormonal therapy.
To talk with others about staying on track with hormonal therapy treatment, join the Breastcancer.org Discussion Board forum Hormonal Therapy - Before, During, and After.
Written by: Jamie DePolo, senior editor
Reviewed by: Brian Wojciechowski, MD, medical adviser
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