6th International Workshop on Breast Densitometry and Breast ...

P20
6 th <strong>International</strong> <strong>Workshop</strong> on Breast Densitometry
and Breast Cancer Risk Assessment
RELATIONSHIP OF SERUM ESTROGEN LEVELS WITH AREA AND VOLUME
MEASURES OF MAMMOGRAPHIC DENSITY AMONG WOMEN UNDERGOING
BREAST BIOPSY FOR CLINICAL INDICATIONS
Gretchen Gierach 1 , Deesha Patel 1 , Roni Falk 1 , Ruth Pfeiffer 1 , Berta Geller 2 , Pamela Vacek 2 , Donald
Weaver 2 , Rachael Chicoine 2 , John Shepherd 3 , Jeff Wang 3 , Bo Fan 3 , Xia Xu 5 , Timothy Veenstra 5 , Barbara
Fuhrman 4 , Louise Brinton 1 , and Mark Sherman 1
1
National Cancer Institute, National Institutes of Health, Rockville, MD, USA; 2 University of Vermont,
Burlington, VT, USA; 3 University of California, San Francisco, San Francisco, CA, USA; 4 University of
Arkansas for Medical Sciences, Little Rock, AR, USA; 5 Frederick National Laboratory for Cancer
Research, SAIC-Frederick, Inc., Frederick, MD, USA
ABSTRACTS
Background: Mammographic density (MD), assessed as the area of non-fatty appearing tissue divided by
the total breast area (MD-A), is an established breast cancer risk factor among pre- and postmenopausal
women. Although increased exposure to estrogens is hypothesized to increase both MD and breast cancer
risk, data relating serum estrogen levels to MD are inconsistent. These inconsistencies may reflect
differences in methods of measuring estrogens, the specific estrogens assessed, and variable techniques
for measuring MD. To elucidate these relationships, we examined the associations of a panel of serum
estrogens and estrogen metabolites (EM), as measured by a newly developed assay, with both area (MD-
A) and volume (MD-V) density measures in a cross-sectional study of women undergoing breast biopsy.
Methods: Pre- and postmenopausal women (n=194), ages 40-65, undergoing a diagnostic image-guided
breast biopsy at a facility of the Vermont Breast Cancer Surveillance System were enrolled (2007-2010).
Serum parent estrogens, estrone (E 1 ) and estradiol (E 2 ), and their 2-, 4-, and 16-hydroxylated metabolites
(conjugated and unconjugated forms, the latter of which are thought to be more biologically available)
were measured using a validated, sensitive liquid chromatography tandem mass spectrometry assay.
Laboratory coefficients of variation were less than 3% for all analytes. MD-A and MD-V were assessed
in craniocaudal views of the breast contralateral to the biopsy target in digital mammograms using
computerized thresholding software (cm 2 ) and single X-ray absorptiometry (mL). Linear regression
models were used to estimate associations of estrogens with square-root transformed MD-A and MD-V,
expressed as absolute values and as percentages of breast area or volume, adjusted for the critical
confounders of age and body mass index. Analyses were stratified by menopausal status and, in
premenopausal women, by menstrual cycle phase.
Results: Among premenopausal women (n=106), circulating levels of most individual EM were not
associated with MD-A or MD-V, although positive associations between percent MD-A and levels of
unconjugated E 1 and unconjugated E 2 were suggested for luteal phase women (E 1 : p=0.08; E 2 : p=0.07).
Among postmenopausal women (n=88), higher circulating levels of unconjugated E 1 showed an
association with increased percent MD-V (p=0.049), but not with MD-A. Higher unconjugated E 2 levels
showed non-significant positive relationships with absolute and percent MD-A and MD-V measures (pvalues
ranged from 0.07-0.11). Levels of the 2-, 4- and 16-hydroxylation pathway EM were positively
associated with MD-A measures (percent MD-A: p=0.009, p=0.02, p=0.02; absolute MD-A: p=0.05,
p=0.09, p=0.03, respectively), but not with MD-V.
Conclusions: Positive associations between serum estrogen profiles and MD were apparent among
women undergoing breast biopsy for clinical indications. Further, our findings suggest that different
measures of MD may provide different information about the biologic underpinnings of breast tissue
composition. Future studies assessing relationships of estrogen metabolites and MD may provide clues
about the etiology of breast cancer.
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