Does breast size modify the association between mammographic density and breast cancer risk?

BACKGROUND: Both the absolute and the percent of mammographic density are strong and independent risk factors for breast cancer. Previously, we showed that the association between mammographic density and breast cancer risk tended to be weaker in African American than in White U.S. women. Because African American women have a larger breast size, we assessed whether the association between mammographic density and breast cancer was less apparent in large than in small breasts. METHODS: We assessed mammographic density on mammograms from 348 African American and 507 White women, 479 breast cancer patients and 376 control subjects, from a case-control study conducted in Los Angeles County. We estimated odds ratios (OR) for breast cancer with increasing mammographic density, and the analyses were stratified by mammographic breast area. RESULTS: Median breast size was 168.4 cm2 in African American women and 121.7 cm2 in White women (P for difference <0.001). For absolute density, adjusted ORs (95% confidence intervals) per increase of 10 cm2 were 1.32 (1.13-1.54), 1.14 (1.03-1.26), and 1.02 (0.98-1.07) in the first, second, and third tertiles of breast area, respectively (P for effect modification by breast area = 0.005). The results for percent density were similar although weaker; adjusted ORs per 10% increase (absolute value) in percent density were 1.22 (1.05-1.40), 1.22 (1.06-1.41), and 1.03 (0.90-1.18 P for effect modification by breast area = 0.34). CONCLUSION: Our results indicate that the association between mammographic density and breast cancer may be weaker in women with larger breasts.

Plasma levels of leptin and mammographic density among postmenopausal women: a cross-sectional study.

INTRODUCTION: Obesity has been linked to increased risk of breast cancer in postmenopausal women. Increased peripheral production of estrogens has been regarded as the main cause for this association, but other features of increased body fat mass may also play a part. Leptin is a protein produced mainly by adipose tissue and may represent a growth factor in cancer. We examined the association between leptin plasma levels and mammographic density, a biomarker for breast cancer risk. METHODS: We included data from postmenopausal women aged 55 and older, who participated in a cross-sectional mammography study in Tromsø, Norway. Mammograms, plasma leptin measurements as well as information on anthropometric and hormonal/reproductive factors were available from 967 women. We assessed mammographic density using a previously validated computer-assisted method. Multiple linear regression analysis was applied to investigate the association between mammographic density and quartiles of plasma leptin concentration. Because we hypothesized that the effect of leptin on mammographic density could vary depending on the amount of nondense or fat tissue in the breast, we also performed analyses on plasma leptin levels and mammographic density within tertiles of mammographic nondense area. RESULTS: After adjusting for age, postmenopausal hormone use, number of full-term pregnancies and age of first birth, there was an inverse association between leptin and absolute mammographic density (P(trend) = 0.001). When we additionally adjusted for body mass index and mammographic nondense area, no statistically significant association between plasma leptin and mammographic density was found (P(trend) = 0.16). Stratified analyses suggested that the association between plasma leptin and mammographic density could differ with the amount of nondense area of the mammogram, with the strongest association between leptin and mammographic absolute density in the stratum with the medium breast fat content (P(trend) = 0.003, P for interaction = 0.05). CONCLUSION: We found no overall consistent association between the plasma concentration of leptin and absolute mammographic density. Although weak, there was some suggestion that the association between leptin and mammographic density could differ with the amount of fat tissue in the breast.

Plasma levels of enterolactone and percentage mammographic density among postmenopausal women.

AIMS: Certain phytoestrogens, such as lignans, may protect against developing breast cancer. Enterolactone is a lignan metabolite produced by the intestinal flora from dietary precursors such as whole grains, vegetables, and fruits. Enterolactone has been shown to have weak estrogenic and antiestrogenic properties. We decided to examine the association between plasma levels of enterolactone and mammographic density, a biomarker for breast cancer risk. METHODS: We included data from postmenopausal women ages 55 and older who participated in a cross-sectional mammogram study in Tromsø, Norway. Mammograms, plasma enterolactone measurements, as well as information on anthropometric and hormonal/reproduction factors were available on 616 women. We assessed mammographic density using a previously validated computer-assisted method. We estimated correlation coefficients and conducted multiple regression analyses. RESULTS: Mean mammographic density increased slightly across quartiles of enterolactone; the women in the highest quartile had, on average, 3.1% (absolute difference) higher percentage mammographic density compared with the lowest quartile (P(trend) < 0.01). After adjustment for age, body mass index, number of full-term pregnancies, age at first birth, and use of postmenopausal hormone therapy, the mean difference in density was reduced to 2.0% (P(trend) = 0.05). Results were similar when restricted to the 454 current hormone nonusers. The fully adjusted statistical model explained 28.3% of the total variability in mammographic percentage density, with body mass index contributing 18.2% and enterolactone only 0.9%. CONCLUSION: In our study, higher levels of enterolactone were associated with slightly higher percentage mammographic density. Our results suggest that if higher enterolactone levels reduce the risk of developing breast cancer in postmenopausal women, then this effect is not through lowering mammographic density.