2 Years of Ovarian Suppression May Be Optimal for Select Patients With ER+ Breast Cancer

2 Years of Ovarian Suppression May Be Optimal for Select Patients With ER+ Breast Cancer

For patients with estrogen-receptor positive breast cancer who remain in a premenopausal state—or resume ovarian function—following chemotherapy, 2 years of ovarian suppression in addition to adjuvant endocrine therapy may be beneficial, according to a long-term follow-up of the ASTRRA trial (NCT00912548), which was published in the Journal of Clinical Oncology.¹

At 106.4 months, or 8 years, of median follow-up time, patients who received ovarian suppression in addition to adjuvant endocrine therapy (n = 610) experienced a continued, significant reduction in disease-free survival (DFS) events compared with patients who received tamoxifen alone (n = 621). The 8-year DFS rate between the 2 arms, respectively, was 85.4% vs 80.2% (HR, 0.67; 95% CI, 0.51-0.87; P = .003).

No significant differences in overall survival (OS) were reported between the 2 groups (HR, 0.78; 95% CI, 0.49-1.25; P = .305). At 8 years, the OS rate between the 2 arms was 96.5% with ovarian suppression and 95.3% in the tamoxifen-only group.

“The ASTRRA trial highlights both the power of ovarian function suppression in young patients with estrogen receptor-positive disease and the overall excellent prognosis in this population,” Soo Yeon Baek, MD, MSs, of the Division of Breast Surgery with the Asan Medical Center in Seoul, and co-investigators, wrote in the study.

Other studies have demonstrated that adding ovarian suppression to adjuvant therapy can be beneficial for women with a higher risk of recurrence. In the SOFT/TEXT trials (NCT00066690/NCT00066703), an 8-year follow-up showed that premenopausal patients who received ovarian suppression to adjuvant tamoxifen achieved significant higher disease-free survival than those who received tamoxifen alone. The SOFT trial also suggested that the addition of ovarian suppression is linked to sustained OS benefits.²

The ASTRRA trial was a randomized controlled trial designed to assess the benefit of 2 years of ovarian suppression in women who were either premenopausal, or who had regained ovarian function after chemotherapy. At a median follow-up of 63 months, patients who received ovarian suppression had improved DFS and OS.¹

The published data are long-term outcomes from the ASTRRA trial, which included 1,483 premenopausal women who were under the age of 45 years. All patients received definitive surgery after completing either adjuvant or neoadjuvant chemotherapy for estrogen-receptor positive disease.

ASTRA enrolled patients from across 35 institutions in South Korea between March 2009 and March 2014. To be eligible to enroll, patients needed to be premenopausal, 45 years or younger, with a diagnosis of stage I-III ER-positive breast cancer.

Optimizing Ovarian Suppression

The study authors acknowledged that the addition of ovarian suppression therapy correlates with heightened endocrine symptoms and worse quality of life.Therefore, to ensure the best care delivery, clinicians should be selective about which patients are prescribed this approach.^1,2

Based on the SOFT/TEXT trial results, 5 years of ovarian suppression are now recommended. However, in ASTRRA follow-up, 95% of patients were alive at the 8-year mark, suggesting that 2 years of ovarian suppression may be acceptable for select patients.

“Considering the significant OS and the potential risk and negative effect on quality of life associated with ovarian function suppression, using ovarian function suppression for 2 years could be acceptable for selected patients,” they wrote.

They went on to point out that ovarian suppression delivery is yet to be optimized. For instance, in the TEXT trial, the therapy was administered during chemotherapy, whereas in SOFT, it was administered post chemotherapy. In the ASTRAA trial, 5.9% of patients (n = 88) did not regain ovarian function within 2 years of chemotherapy completion.

Because age is a key factor in whether a patient recovers ovarian function after chemotherapy, study authors argue that the optimal starting point of ovarian suppression may also depend on age. For patients who are 40 years or younger, beginning ovarian suppression concurrently, or immediately following chemotherapy was shown to be beneficial in the SOFT/TEXT trials. Suppressing ovarian function during chemotherapy has also been shown to help preserve ovarian function and fertility—which is often a concern for younger patients.

In comparison, for patients who are 40 years or older, waiting until after confirming that the patient has recovered ovarian function may be the most economically suitable approach, study authors said.

“Personalizing treatment decisions requires an individual risk assessment and consideration of long-term toxicities,” they concluded. “The study findings support the possibility of endocrine therapy tailored to an appropriate subset of women who may benefit from adding 2 years of ovarian function suppression to tamoxifen.”

References

1. Baek SY, Noh WC, Ahn SH, et al. Adding ovarian suppression to tamoxifen for premenopausal women with hormone receptor-positive breast cancer after chemotherapy: an 8-Year Follow-Up of the ASTRRA Trial. J Clin Oncol. 2023;JCO2300557. doi:10.1200/JCO.23.00557
2. Francis PA, Pagani O, Fleming GF, et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379(2):122-137. doi:10.1056/NEJMoa1803164