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.
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.


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 (> or =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).


CONCLUSIONS
Switching from tamoxifen to exemestane significantly reverses endometrial thickening associated with continued tamoxifen.
Bertelli
G
G
Department of Oncology, Singleton Hospital, South West Wales Cancer Institute, Swansea. Electronic address: gianfilippo.bertelli@swansea-tr.wales.nhs.uk.
Hall
E
E
ICR-CTSU, Section of Clinical Trials, Institute of Cancer Research, Sutton, UK.
Ireland
E
E
ICR-CTSU, Section of Clinical Trials, Institute of Cancer Research, Sutton, UK.
Snowdon
C F
CF
ICR-CTSU, Section of Clinical Trials, Institute of Cancer Research, Sutton, UK.
Jassem
J
J
Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.
Drosik
K
K
Department of Oncology, Regional Cancer Center, Opole, USA.
Karnicka-Mlodkowska
H
H
Department of Chemotherapy, Maritime Hospital, Gdynia, Poland.
Coombes
R C
RC
Cancer Research UK Department of Cancer Medicine, Imperial College London, Hammersmith Hospitals Trust, London, UK.
Bliss
J M
JM
ICR-CTSU, Section of Clinical Trials, Institute of Cancer Research, Sutton, UK.
D000368:Aged; D000730:Androstadienes / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000473:pathology; D004311:Double-Blind Method; D016889:Endometrial Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007390:International Agencies; D008875:Middle Aged; D017698:Postmenopause; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography
D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D013629:Tamoxifen; C056516:exemestane