Higher than expected estradiol levels in aromatase inhibitor-treated, postmenopausal breast cancer patients.
OBJECTIVE
Vaginal estradiol is considered contraindicated in aromatase inhibitor (AI)-treated patients because of the risk of elevated estrogen levels. This leaves limited treatment options for patients experiencing gynecological symptoms. However, in clinical practice, no precise estimation has been performed of circulating estrogens and aromatase index in postmenopausal breast cancer patients on long-lasting AI or tamoxifen treatment.


METHODS
Steroid hormones were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) and extraction radioimmunoassay (RIA). Postmenopausal AI-treated patients (n =33) were compared with tamoxifen-treated patients (n =34) and controls without vaginal treatment (n =56), with vaginal estradiol (n =25), or with estriol (n =11) treatment.


RESULTS
By use of LC-MS/MS, median (range) estradiol plasma concentrations were 16.7 (2.4-162.6), 31.0 (13.4-77.1), 27.2 (7.8-115.8) and 33.3 (20.3-340.1) pmol/l in AI-treated breast cancer patients, tamoxifen-treated breast cancer patients, postmenopausal controls and postmenopausal controls on vaginal estradiol, respectively. The AI-treated group and subgroups had significantly lower estradiol and estrone concentrations than all other groups (p <0.05). There was extensive interindividual variation in estradiol concentration within the AI-treated group, measured using both LC-MS/MS (2.3-182.0 pmol/l) and extraction RIA (2.4-162.6 pmol/l). The AI-treated group had lower aromatase index compared to all other groups (p <0.05-0.001).


CONCLUSIONS
Circulating estrogen levels may have been underestimated in previous longitudinal studies of AI-treated breast cancer patients. Additional studies are required to further evaluate the role of circulating estrogens in breast cancer patients suffering from gynecological symptoms.
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
T
T
Kunovac Kallak
J
J
Baumgart
A
A
Stavreus Evers
I
I
Sundström Poromaa
L
L
Moby
K
K
Kask
E
E
Norjavaara
M M
MM
Kushnir
J
J
Bergquist
K
K
Nilsson
D000282:Administration, Intravaginal; D000368:Aged; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D003430:Cross-Sectional Studies; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood*; D004964:Estriol / Q000008:administration & dosage / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D013629:Tamoxifen / Q000627:therapeutic use
D047072:Aromatase Inhibitors; D013629:Tamoxifen; D004958:Estradiol; D001141:Aromatase; D004964:Estriol