In a long-term analysis of the TEXT/SOFT trials reported in the Journal of Clinical Oncology, Pagani et al found that potential benefits of escalating adjuvant endocrine therapy beyond tamoxifen alone in preventing distant recurrence may be minimal in premenopausal women with hormone receptor–positive, HER2-negative breast cancer who are identified as being at low risk of recurrence.

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Overall, the TEXT/SOFT trials showed better outcomes with adjuvant exemestane plus ovarian function suppression or tamoxifen plus ovarian function suppression vs tamoxifen alone.

Study Details

The study determined absolute improvements in 8-year freedom from distant recurrence among 4,891 women stratified by predetermined chemotherapy use. Estimates of freedom from distant recurrence were determined using subpopulation treatment effect pattern plot analysis across subpopulations defined by a continuous composite measure of recurrence risk. For each patient, a composite risk value was obtained from a model that incorporated age; nodal status; tumor size and grade; and estrogen receptor, progesterone receptor, and Ki-67 labeling index expression levels.

Key Findings

Overall, the 8-year rate of freedom from distant recurrence was 91.1% among all women, with rates ranging from approximately 100% to 63% across lowest to highest composite risk values. Patients in the TEXT trial who received chemotherapy had an average 8-year freedom from distant recurrence rate of 87.5%. An average absolute improvement of 5.1% in the 8-year rate was observed with exemestane plus ovarian function suppression vs tamoxifen plus ovarian function suppression, with improvements ranging from < 1% to > 15% across lowest to highest composite risk levels.

Patients in the SOFT trial who remained premenopausal after chemotherapy had an average 8-year freedom from distant recurrence rate of 82.5%. A 5.2% absolute improvement was observed with exemestane plus ovarian function suppression vs tamoxifen; findings suggested that patients across all composite risk levels experienced benefit from exemestane plus ovarian function suppression, with a maximum absolute improvement of approximately 10% at highest composite risk levels. The maximum improvement with tamoxifen plus ovarian function suppression vs tamoxifen was approximately 3.5%.

Among women who did not receive chemotherapy, 8-year freedom from distant recurrence was > 97%. In this group, improvements with exemestane plus ovarian function suppression ranged from 1% to 4% across lowest to highest composite risk values.

The investigators concluded, “Premenopausal women with [hormone receptor]-positive/HER2-negative breast cancer and high recurrence risk, as defined by clinicopathologic characteristics, may experience a 10% to 15% absolute improvement in 8-year freedom from distant recurrence with exemestane plus ovarian function suppression vs tamoxifen plus ovarian function suppression or tamoxifen alone. The potential benefit of escalating endocrine therapy vs tamoxifen alone is minimal for those at low recurrence risk.”

Meredith M. Regan, ScD, of the International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Pfizer, International Breast Cancer Study Group, US National Cancer Institute, Breast Cancer Research Foundation for Tamoxifen and Exemestane Trial and Suppression of Ovarian Function Trial conduct, and others. For full disclosures of the study authors, visit jco.ascopubs.org.