Ovarian Suppression 'Triumphant' for Premenopausal Hormonally Sensitive Breast Cancers

Lidia Schapira, MD


August 30, 2018

Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer

Francis PA, Pagani O, Fleming GF, et al; SOFT and TEXT Investigators and the International Breast Cancer Study Group
N Engl J Med. 2018;379:122-137

Study Summary

This study provides an update on results from the SOFT and TEXT studies of hormonal therapies for premenopausal women. Both studies accrued patients between 2003 and 2011.

The SOFT trial was designed to determine the value of adding ovarian suppression (OS) to tamoxifen and to study the role of the aromatase inhibitor exemestane plus OS. Women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus OS, or exemestane plus OS in SOFT.

The TEXT trial was designed to compare tamoxifen with exemestane for women treated with OS from the time of their breast cancer diagnosis, in addition to other disease-modifying therapies such as chemotherapy. Women were randomly assigned to receive tamoxifen plus OS or exemestane plus OS in TEXT.

Prior publications reported results of the SOFT study with a median follow-up of 5.6 years, and these did not show a significantly higher disease-free survival (DFS) with the addition of OS to tamoxifen compared with tamoxifen alone, although the addition of OS did demonstrate an improvement in outcomes for women also treated with chemotherapy. Results of the combined SOFT and TEXT analyses at that time showed that exemestane plus OS had significantly higher rates of DFS than tamoxifen plus OS.

In the current study, investigators report the updated results from the two trials.

In SOFT, the 8-year disease-free survival rate was 79% with tamoxifen alone, 83% with tamoxifen plus OS, and 86% with exemestane plus OS. The 8-year overall survival rate was 91.5% with tamoxifen alone, 93% with tamoxifen plus OS, and 92% with exemestane plus OS.

Among the women who remained premenopausal after chemotherapy, the rates were 85%, 89%, and 87%, respectively. Among women with HER2-negative cancers who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus OS was lower than the rate with tamoxifen plus OS (by 7 percentage points in SOFT and by 5 percentage points in TEXT).

Grade 3 or higher adverse events were reported in 25% of the tamoxifen-alone group, 31% of the tamoxifen-OS group, and 32% of the exemestane-OS group.

The investigators concluded that among premenopausal women with breast cancer, the addition of OS to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus OS resulted in even higher rates of freedom from recurrence. However, the adverse event rates were higher in the two groups that received OS than in the tamoxifen-alone group.


Fifteen years after starting accrual for these trials, we are finally seeing a more complete answer to the initial study questions. OS has emerged triumphant and there is now no doubt that it can improve outcomes for premenopausal women with hormonally sensitive cancers when combined with tamoxifen or an aromatase inhibitor, and that the benefits are more marked for women with high-grade tumors and an earlier age at initial diagnosis.

The challenge for oncologists now is how to counsel and help patients remain on maintenance therapies despite experiencing significant side effects that affect their quality of life. I was surprised by the high numbers of patients who discontinued therapy, even in the setting of a highly publicized international trial.

So how can oncologists promote the putative benefits while remaining realistic about the expected and commonly associated side effects of endocrine therapies when talking to their younger patients?

It's time for us to engage in more proactive communication strategies by providing information, education, and frequent coaching to women who struggle to maintain their vitality, youth, and optimism after a cancer diagnosis. There are behavioral and lifestyle interventions, as well as pharmacologic therapies, that can ameliorate most of the side effects from endocrine therapies. We need to find ways of supporting young women so that they can complete the intended course of treatment and thus derive the full benefit demonstrated by these rigorous international studies.



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