The TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) studies were complementary phase III, randomized clinical trials that evaluated premenopausal women with hormone receptor—positive early breast cancer. In both trials, all patients received ovarian suppression. In TEXT, patients were randomized to receive either tamoxifen or exemestane if chemotherapy was given. In SOFT, patients were randomized to receive tamoxifen alone or ovarian suppression with tamoxifen or exemestane.

A joint analysis of the two studies demonstrated that adjuvant use of ovarian function suppression plus exemestane reduced the relative risk of developing subsequent invasive cancer by 28% compared with tamoxifen, according to findings presented at the 2014 ASCO Annual Meeting. Cancer-free survival at 5 years was 91.1% in the exemestane arm compared with 87.3% in the tamoxifen arm. Similar 5-year overall survival rates occurred in both arms, with a 95.9% survival with exemestane compared with 96.9% with tamoxifen.

The rationale for the study was based on evidence that patients with high-risk, estrogen receptor—positive disease may benefit from ovarian suppression and tamoxifen, followed by a switch to exemestane therapy. This strategy spares individuals from experiencing too many adverse events at once, explains Hope S. Rugo, MD.

Monitoring serum estradiol levels in 30-year-old individuals with high-risk disease is important, as these levels are believed to be part of tumor control, Sara Hurvitz, MD, mentions. Additionally, ovarian suppression plays an important role in high-risk premenopausal patients. Patients in their 30s and 40s need to consider the long-term side effects of these therapies, and clinicians must convince women that the benefits outweigh the risks, emphasizes Dialecti Voudouris, MD.