A substudy of the SOFT trial found that a number of patients assigned to adjuvant treatment with the aromatase inhibitor exemestane plus triptorelin do not achieve complete reductions in their estrogen levels.
Most premenopausal women with hormone receptor–positive breast cancer assigned to adjuvant treatment with the aromatase inhibitor exemestane plus triptorelin had large reductions in estrogen levels (estradiol [E2]) during the first year of treatment, according to the results of a preplanned interim analysis of the SOFT-EST substudy. However, one-third of patients had E2 levels that measured greater than 2.72 pg/mL, a strict threshold to indicate E2 inconsistent with postmenopausal levels seen on an aromatase inhibitor, at least once during the first year of treatment.
“The findings of this substudy should be viewed in light of the results of SOFT and TEXT trials,” wrote researchers led by Meritxell Bellet, MD, Vall d’Hebron Institute of Oncology and Vall d’Hebron University Hospital and SOLTI Group.
“The SOFT and TEXT combined analysis showed improved disease-free survival with exemestane plus ovarian function suppression compared with tamoxifen plus ovarian function suppression, whereas the SOFT trial showed benefits in freedom from breast cancer with tamoxifen plus ovarian function suppression compared with tamoxifen alone, which were further improved with exemestane plus ovarian function suppression in patients who received prior chemotherapy and in the youngest patients,” Bellet and colleagues wrote in the Journal of Clinical Oncology.
“Considering that treatment with a GnRHa plus aromatase inhibitor will be increasingly adopted, knowing whether a patient has suboptimal estrogen suppression in real time will become clinically important.”
The substudy looked at 116 premenopausal women enrolled in the SOFT study who selected triptorelin as a method of ovarian suppression and were then randomly assigned to exemestane plus triptorelin (n = 86) or tamoxifen plus triptorelin (n = 30). Blood samples were scheduled to be taken at 0, 3, 6, 12, 18, 24, 36, and 48 months. The 12-month analysis looked at levels of E2, estrone (E1), and estrone sulfate (E1S).
The researchers found that patients taking exemestane plus triptorelin had significantly lower levels of E2, E1 and E1S than did patients assigned tamoxifen plus triptorelin. Median reductions in these levels were consistently greater than 95% with exemestane.
However, certain patients assigned exemestane still had E2 levels that were greater than the 2.72 pg/mL threshold. At 3 months, 25% of patients assigned exemestane had levels above this threshold; at 6 months, 24%; and at 12 months, 17%.
The researchers conducted an analysis to identify factors associated with levels greater than 2.72 pg/mL and found associations with no prior chemotherapy (P = .06), higher body mass index (P = .05), and lower follicle-stimulating hormone (FSH) and luteinizing hormone (LH; P < .01 for both).
“The analysis of potential predictive factors for suboptimal suppression, albeit exploratory, reinforces the additional role of FSH and LH levels to better define a truly premenopausal status, particularly after chemotherapy, which is superior to that provided by locally assessed E2 levels that defined eligibility for the SOFT trial,” the researchers wrote. “Even with serial estrogen and gonadotropin assessments, establishing a definitive menopausal status remains elusive, and the possibility of a later recovery still exists, as illustrated by E2 levels greater than 2.72 pg/mL observed during triptorelin plus exemestane among women with baseline postmenopausal levels.”