Suppression of Plasma Estrogen Levels by Letrozole and
Anastrozole Is Related to Body Mass Index in Patients With
Elizabeth J. Folkerd, J. Michael Dixon, Lorna Renshaw, Roger P. A’Hern, and Mitch Dowsett
See accompanying editorial on page 2940
Elizabeth J. Folkerd and Mitch Dowsett,
Royal Marsden Hospital, London; J.
Michael Dixon and Lorna Renshaw,
Western General Hospital, Edinburgh;
and Roger P. A’Hern, Institute for
Cancer Research, Sutton, United Kingdom.
Submitted January 26, 2012; accepted
May 15, 2012; published online ahead
of print at www.jco.org on July 16,
Authors’ disclosures of potential con-
flicts of interest and author contribu-
tions are found at the end of this
Corresponding author: Elizabeth J.
Folkerd, PhD, Academic Department of
Biochemistry, The Royal Marsden NHS
Foundation Trust, Fulham Rd, London,
SW3 6JJ, United Kingdom; e-mail:
© 2012 by American Society of Clinical
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.
Patients and 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.
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.
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.
J Clin Oncol 30:2977-2980. © 2012 by American Society of Clinical Oncology
to be a risk factor for breast cancer in postmeno-
pausal women.1Recent reports2,3have demon-
strated an association between obesity and both
breast cancer–specific mortality, in women with
breast cancer. Understanding the impact and effi-
overweight is an important area for investigation:
the findings could result in the modification of
therapeutic regimens and improvement in out-
come for obese women with breast cancer. Two
higher BMI experience reduced efficacy of the
aromatase inhibitor (AI) anastrozole relative to
tamoxifen when these drugs are administered as
adjuvant therapy for early estrogen receptor (ER)
–positive breast cancer.
Postmenopausal women with ER-positive
moxifen, Alone or in Combination (ATAC) trial
had a greater chance of recurrence and death after
zole compared with tamoxifen was less in over-
recurrence was 0.59 (95% CI, 0.39 to 0.89) in favor
those with a BMI of greater than 30 kg/m2. More
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