Suppression of plasma estrogen levels by letrozole and anastrozole is related to body mass index in patients with breast cancer.
OBJECTIVE
To investigate whether suppression of plasma estradiol and estrone sulfate levels by the aromatase inhibitors (AIs) anastrozole and letrozole is related to body mass index (BMI) in postmenopausal women with early estrogen receptor (ER) -positive breast cancer. Recent studies have reported that the AI anastrozole has lower effectiveness than tamoxifen in women with high BMI. This effect with high BMI might hypothetically be a result of reduced inhibition of aromatase and suppression of plasma estrogen levels and might be overcome by the use of an increased dose of anastrozole or, alternatively, the use of a more potent AI such as letrozole.


METHODS
Plasma estradiol and estrone sulfate levels from a highly sensitive radioimmunoassay were available for 44 postmenopausal patients who received anastrozole (1 mg per day) for 3 months followed by letrozole (2.5 mg per day) for 3 months or the opposite sequence. Correlations between the estrogen suppression by each AI and BMI were assessed.


RESULTS
Baseline values of estradiol and estrone sulfate were significantly correlated with BMI (r = 0.57; P < .001, and r = 0.38; P = .006, respectively). Levels of estrogen in patients receiving treatment were greater at higher levels of BMI with both AIs, but although this was significant with letrozole (r = 0.35; P = .013, and r = 0.30; P = .035 for estradiol and estrone sulfate, respectively), it was not with anastrozole. Suppression of both estrogen types was greater with letrozole across the full range of BMIs in this study.


CONCLUSIONS
The suppressed levels of plasma estradiol and estrone sulfate in postmenopausal women with early ER-positive breast cancer treated with the AIs anastrozole and letrozole are related to BMI.
Royal Marsden Hospital, London, United Kingdom. Elizabeth.Folkerd@icr.ac.uk
Elizabeth J
EJ
Folkerd
J Michael
JM
Dixon
Lorna
L
Renshaw
Roger P
RP
A'Hern
Mitch
M
Dowsett
D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology*; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy*; D004967:Estrogens / Q000097:blood*; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000097:blood* / Q000188:drug therapy; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*; D017698:Postmenopause; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D004970:Estrone; D000077384:Anastrozole; D000077289:Letrozole; C017296:estrone sulfate