Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer

Publication

Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer

Journal Paper/Review - Jun 4, 2018

Francis Prudence A, Pavesi Lorenzo, Ruhstaller Thomas, Davidson Nancy E, Coleman Robert, Debled Marc, Buchholz Stefan, Ingle James N, Winer Eric P, Maibach Rudolf, Rabaglio-Poretti Manuela, Ruepp Barbara, Di Leo Angelo, Coates Alan S, Gelber Richard D, Goldhirsch Aron, Regan Meredith M, Climent Miguel A, Spazzapan Simon, Puglisi Fabio, Pagani Olivia, Fleming Gini F, Walley Barbara A, Colleoni Marco, Láng István, Gomez Henry L, Tondini Carlo, Ciruelos Eva, Burstein Harold J, Bonnefoi Hervé R, Bellet Meritxell, Martino Silvana, Geyer Charles E, Goetz Matthew P, Stearns Vered, Pinotti Graziella, SOFT and TEXT Investigators and the International Breast Cancer Study Group

Citation

Francis P, Pavesi L, Ruhstaller T, Davidson N, Coleman R, Debled M, Buchholz S, Ingle J, Winer E, Maibach R, Rabaglio-Poretti M, Ruepp B, Di Leo A, Coates A, Gelber R, Goldhirsch A, Regan M, Climent M, Spazzapan S, Puglisi F, Pagani O, Fleming G, Walley B, Colleoni M, Láng I, Gomez H, Tondini C, Ciruelos E, Burstein H, Bonnefoi H, Bellet M, Martino S, Geyer C, Goetz M, Stearns V, Pinotti G, SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. N Engl J Med 2018; 379:122-137.

Type

Journal Paper/Review (English)

Journal

N Engl J Med 2018; 379

Publication Date

Jun 4, 2018

Issn Electronic

1533-4406

Pages

122-137

Brief description/objective

BACKGROUND
In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials.

METHODS
Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy.

RESULTS
In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression). The 8-year rate of overall survival was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression, and 92.1% with exemestane plus ovarian suppression (P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression); among the women who remained premenopausal after chemotherapy, the rates were 85.1%, 89.4%, and 87.2%, respectively. Among the women with cancers that were negative for HER2 who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression (by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT). Grade 3 or higher adverse events were reported in 24.6% of the tamoxifen-alone group, 31.0% of the tamoxifen-ovarian suppression group, and 32.3% of the exemestane-ovarian suppression group.

CONCLUSIONS
Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group. (Funded by Pfizer and others; SOFT and TEXT ClinicalTrials.gov numbers, NCT00066690 and NCT00066703 , respectively.).