Long-term endometrial effects in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES)—a randomised controlled trial of exemestane versus continued tamoxifen after 2–3 years tamoxifen

Abstract

Background: The antiestrogen tamoxifen may have partial estrogen-like effects on the postmenopausal uterus. Aromatase inhibitors (AIs) are increasingly used after initial tamoxifen in the adjuvant treatment of postmenopausal early breast cancer due to their mechanism of action: a potential benefit being a reduction of uterine abnormalities caused by tamoxifen. Patients and methods: Sonographic uterine effects of the steroidal AI exemestane were studied in 219 women participating in the Intergroup Exemestane Study: a large trial in postmenopausal women with estrogen receptor-positive (or unknown) early breast cancer, disease free after 2–3 years of tamoxifen, randomly assigned to continue tamoxifen or switch to exemestane to complete 5 years adjuvant treatment. The primary end point was the proportion of patients with abnormal (≥5 mm) endometrial thickness (ET) on transvaginal ultrasound 24 months after randomisation. Results: The analysis included 183 patients. Two years after randomisation, the proportion of patients with abnormal ET was significantly lower in the exemestane compared with tamoxifen arm (36% versus 62%, respectively; P = 0.004). This difference emerged within 6 months of switching treatment (43.5% versus 65.2%, respectively; P = 0.01) and disappeared within 12 months of treatment completion (30.8% versus 34.7%, respectively; P = 0.67). Conclusion: Switching from tamoxifen to exemestane significantly reverses endometrial thickening associated with continued tamoxifen.

Aromatase inhibitor therapy: toxicities and management strategies in the treatment of postmenopausal women with hormone-sensitive early breast cancer

“…In patients who switched to anastrozole following 2 years of tamoxifen (n = 1,618), there was only 1 case of endometrial cancer [78]. An endometrial IES substudy in 219 patients showed that abnormal endometrial thickening (C5 mm) was observed within 6 months in 36% of patients receiving exemestane; the incidence of endometrial cancer was not reported [17]. In the sequential groups of the BIG 1-98 trial, endometrial cancer developed in 4 patients (0.1%) [31].…”

Adherence to oral endocrine treatments in women with breast cancer: can it be improved?

“…Thus, if a subject is considering discontinuing tamoxifen due to adverse effects, they may be changed to treatment with the aromatase inhibitors, or vice versa. For instance, endometrial thickening associated with tamoxifen use, determined by transvaginal ultrasound, was reversed in subjects swapped to exemestane in the IES [36]. However, there is no evidence that such a change improves adherence to oral endocrine therapy.…”

Evaluation of Endometrial Thickness and Bone Mineral Density Based on CYP2D6 Polymorphisms in Turkish Breast Cancer Patients Receiving Tamoxifen Treatment

“…Numerous studies have investigated CYP2D6 polymorphism, demonstrating the role of tamoxifen metabolism in determining the risk of breast cancer recurrence. Specific side effects of tamoxifen have been associated with CYP2D6 mutations [1,2,3,4,5,6,7,8,9,10,11,12,13,14,17,18,19]. …”

“…The use of tamoxifen may also result in changes to the lipid profile [8,9,10], bone mineral density (BMD) [11], and endometrial thickness (ET) [12,13]. …”

“…A significant increase in ET was observed at 1 year following tamoxifen treatment and was attributed to the partial estrogenic effects of the drug [12,13]. Previous studies have investigated the relationship between CYP2D6 polymorphisms and the risk of side effects during tamoxifen treatment [14,15,16].…”