From the Guidelines
The additional benefit of ovarian suppression and aromatase inhibitors (AIs) over tamoxifen in adjuvant therapy for breast cancer is a reduction in recurrence risk, particularly in premenopausal women with high-risk hormone receptor-positive breast cancer.
Key Findings
- The TEXT and SOFT trials showed that exemestane plus ovarian suppression reduced recurrences compared with tamoxifen plus ovarian suppression in premenopausal women with hormone receptor-positive early-stage breast cancer 1.
- The 9-year median follow-up analysis of the TEXT-SOFT trials demonstrated sustained improvements in disease-free survival (DFS) with exemestane plus ovarian suppression versus tamoxifen plus ovarian suppression (HR, 0.77; 95% CI, 0.67-0.90) 1.
- The ASTRRA trial also showed a benefit of ovarian suppression in premenopausal patients with high risk of recurrence, with an 8-year DFS of 85.4% versus 80.2% with tamoxifen alone (HR, 0.67; 95% CI, 0.51-0.87) 1.
Benefits and Risks
- The addition of ovarian suppression to standard adjuvant therapy with tamoxifen or with an aromatase inhibitor improved DFS and freedom from breast cancer and distant recurrence compared with tamoxifen alone among high-risk patients 1.
- However, ovarian suppression was associated with a substantial increase in menopausal symptoms, sexual dysfunction, and diminished quality of life 1.
Clinical Implications
- The NCCN panel recommends ovarian suppression plus endocrine therapy for 5 years as an option for premenopausal patients with hormone receptor-positive breast cancer at higher risk of recurrence (e.g., young age, high-grade tumor, lymph node involvement) 1.
- Premenopausal patients wishing to continue adjuvant endocrine therapy after ovarian suppression is stopped should continue with tamoxifen versus AI 1.
The FDA Drug Labels for tamoxifen (PO) do not address this question.
From the Research
Additional Benefit of Ovarian Suppression and Aromatase Inhibitors
The additional benefit of ovarian suppression and aromatase inhibitors (AIs) over tamoxifen in adjuvant therapy for breast cancer can be summarized as follows:
- A study published in 2022 2 found that premenopausal women treated with ovarian suppression benefit from aromatase inhibitors, with a reduced risk of breast cancer recurrence.
- The same study found that the main benefit of aromatase inhibitors was seen in the first 4 years of treatment, with a 3.2% absolute reduction in 5-year recurrence risk.
- A meta-analysis published in 2020 3 found no statistical differences between AIs plus ovarian function suppression and tamoxifen plus ovarian function suppression in disease-free survival and overall survival.
- However, a network meta-analysis published in 2021 4 found that ovarian function suppression plus tamoxifen improved 5-year disease-free survival and 5-year overall survival compared with tamoxifen monotherapy.
- The same network meta-analysis found that ovarian function suppression plus aromatase inhibitor improved 5-year disease-free survival, but not 5-year overall survival.
Key Findings
Key findings from the studies include:
- Ovarian suppression and aromatase inhibitors can reduce the risk of breast cancer recurrence in premenopausal women 2.
- The benefit of aromatase inhibitors is mainly seen in the first 4 years of treatment 2.
- Ovarian function suppression plus tamoxifen may be a better option than ovarian function suppression plus aromatase inhibitor for premenopausal intensive adjuvant endocrine therapy 4.
- Stage III patients may be more suitable for ovarian function suppression-based therapy 4.
Treatment Considerations
Treatment considerations based on the studies include:
- The use of ovarian function suppression is standard of care for most premenopausal women with estrogen receptor-positive disease, except for those with low-risk clinical-pathological features 5.
- The choice of endocrine agent to partner with ovarian function suppression depends on the risk of disease recurrence, with aromatase inhibitors being more beneficial for higher-risk patients 5.