Blocking Ovarian Function Benefits Some Young Women
The largest study of long-term breast cancer treatment using methods to stop estrogen production in premenopausal women with hormone receptor-positive disease has found what one of its authors calls “practice-changing” results for certain women.
Those younger than 35, who had chemotherapy and remained premenopausal, had their risk of cancer returning lowered significantly by receiving ovarian suppression treatment and an aromatase inhibitor for 5 years.
The research, conducted by the International Breast Cancer Study Group, was presented at the 2014 San Antonio Breast Cancer Symposium and published in the New England Journal of Medicine.
LBBC reported on preliminary results of this study in August 2014.
Background and Goals
Chemotherapy can shut down estrogen production in the ovaries, temporarily or permanently. Women who are premenopausal after chemotherapy continue to produce ovarian estrogen. For those with HR-positive breast cancer, which is fueled by estrogen, this increases risk of recurrence, or cancer returning. In younger premenopausal women, chemotherapy is less likely to stop ovarian estrogen permanently.
Tamoxifen, a hormonal medicine that blocks ovarian estrogen, is standard adjuvant treatment, given after initial therapy, for premenopausal women with breast cancer. It lowers recurrence risk. Postmenopausal women no longer make estrogen in their ovaries and may take either tamoxifen or an aromatase inhibitor, or AI, to stop estrogen production elsewhere in their bodies.
Ovarian suppression treatment, including the medicine triptorelin (Trelstar) and surgery to remove the ovaries, has been studied in premenopausal women. Its effectiveness when used with tamoxifen has not been clearly established.
This study, the Suppression of Ovarian Function Trial (SOFT), was looking to see if tamoxifen plus ovarian suppression would improve disease-free survival, DFS, for premenopausal women, compared to tamoxifen alone. It also wanted to know if exemestane (Aromasin), an AI, plus ovarian suppression would be beneficial, compared to tamoxifen alone and tamoxifen plus ovarian suppression.
The research studied 3,066 premenopausal women diagnosed with early-stage, HR-positive breast cancer. The women were randomly assigned into treatment groups. The therapies were
- tamoxifen alone
- tamoxifen plus ovarian suppression (triptorelin or surgery)
- exemestane plus ovarian suppression (triptorelin or surgery)
Nearly 47 percent of the women had no chemotherapy. These women were mostly older (median age, 46) and still premenopausal.
About 53 percent of women were treated with chemotherapy, yet remained premenopausal. They had a median age of 40. About 20 percent were under 35. Only six percent of all women under age 35 in the study received no chemotherapy.
For women who had chemotherapy and remained premenopausal
- treatment with exemestane-ovarian suppression was found significantly more effective than tamoxifen-ovarian suppression or tamoxifen alone
- exemestane-ovarian suppression was especially beneficial for the highest-risk women, those under 35
The study also found that adding ovarian suppression to tamoxifen lowered recurrence compared to tamoxifen alone, but that finding was not statistically significant. That means the difference could be because of chance or factors other than the treatment itself.
The researchers noted longer follow-up is needed to better understand benefits.
What This Means For You
For many premenopausal women with early-stage, HR-positive breast cancer, tamoxifen by itself continues to be an appropriate long-term treatment after initial therapy.
If you have been – or will be – treated with chemotherapy, and are premenopausal, talk with your oncologist about this study. You may want to consider ovarian suppression treatment plus exemestane to further lower your risk of cancer returning.
Tamoxifen, exemestane and ovarian suppression all can cause side effects, including menopausal symptoms, depression, joint and bone problems, sexual difficulties and more. These are issues to consider when evaluating which treatment is best for you. Talk with your healthcare team about ways to manage side effects. The LBBC Breast Cancer Helpline also can help answer your questions.
Francis, P, Regan, M, Fleming, G, Láng, I, Ciruelos, E, et al. Adjuvant Ovarian Suppression in Breast Cancer. The New England Journal of Medicine. Published ahead of print in December 2014. DOI: 10.1056/NEJMoa1412379.
This article wassupported by the Grant or Cooperative Agreement Number 1 U58 DP005403,funded by the Centers for Disease Control and Prevention. Its contents aresolely the responsibility of the authors and do not necessarily represent theofficial views of the Centers for Disease Control and Prevention or theDepartment of Health and Human Services.