Mammographic density in a multiethnic cohort.

OBJECTIVES: To compare mammographic density among premenopausal and early perimenopausal women from four racial/ethnic groups and to examine density and acculturation among Japanese and Chinese women. DESIGN: The study included 391 white, 60 African American, 171 Japanese, and 179 Chinese participants in the Study of Women's Health Across the Nation, a multisite study of US women transitioning through menopause. Mammograms done when women were premenopausal or early perimenopausal were assessed for area of dense breast tissue and the percent of the breast occupied by dense tissue (percent density). Information on race/ethnicity, acculturation, and other factors was obtained from standardized instruments. Multiple linear regression modeling was used to examine the association between race/ethnicity or acculturation and density measures. RESULTS: Age-adjusted mean percent density was highest for Chinese (52%) and lowest for African American (34%) women. After additional adjustment for body mass index, menopause status, age at first birth, breast-feeding duration, waist circumference, and smoking, African Americans had the highest mean percent density (51%) and Japanese women had the lowest (39%). In contrast, the area of dense tissue was highest for African Americans and similar for white, Japanese, and Chinese women. Less acculturated Chinese and Japanese women tended to have a larger area of density and a higher percent density. CONCLUSIONS: Neither the age-adjusted nor fully adjusted results for percent density or area of dense tissue reflected current differences in breast cancer incidence rates among similarly aged African American, Japanese, Chinese, and white women. In addition, mammographic density was higher in less acculturated Asian women.

Mammographic density and breast cancer in three ethnic groups.

The extent of radiodense tissue on a mammogram (mammographic densities) is strongly associated with breast cancer risk among (non-Latina) white women, but few data exist for African-American and Asian-American women. We collected prediagnostic mammograms from 622 breast cancer patients and 443 control subjects ages 35-64 years from three different ethnic groups (whites, African Americans, and Asian Americans) who participated as cases and controls in one of two ongoing breast cancer studies. Percent and absolute mammographic density were assessed using a previously validated computer-assisted method. In all three ethnic groups combined, breast cancer risk increased with increasing percent mammographic density. After adjustment for ethnicity, age, body mass index, age at menarche, breast cancer family history, age at and number of full-term pregnancies, menopausal status, and hormone replacement therapy use, women with the highest percent density had 5-fold greater breast cancer risk than women with no density (P(trend) = 0.0001). The impact of percent density on risk was stronger for older than for younger women (>/=50 versus <50 years; P = 0.05). Risk estimates did not differ significantly by ethnicity, with breast cancer risk (95% confidence interval) increasing 15% (4-27%) in whites, 30% (5-61%) in Asian Americans, and 11% (-2-26%) in African Americans for each 10% increase in density. The trends were similar for absolute density. Our results confirm that increases in computer-assisted mammographic density measurements are associated with a strong gradient in breast cancer risk. Furthermore, our findings suggest that mammographic density is as strong a predictor of risk for African-American and Asian-American women as for white women.

Genetic determinants of mammographic density.

BACKGROUND: Changes in breast density are highly correlated with steroid hormone exposure. MATERIALS AND METHODS: In a cross-sectional study of 396 Caucasian and African-American women, we evaluated whether polymorphisms in genes involved in steroid hormone biosynthesis and metabolism, CYP17 (T27C), COMT (Val158Met), 17HSDB1 (Ser312Gly) and 3HSDB1 (Asn367Thr), predict mammographic density. We also evaluated whether associations vary by menopausal and hormone replacement therapy status. RESULTS: We found no strong consistent relationships between polymorphisms in these genes and breast density. African-American women homozygous for the Thr allele of 3HSDB1 had increased density (the absolute difference versus the Asn/Asn genotype was +19.7%; P trend = 0.02), while Caucasian homozygous women had decreased density (-5.1%; P trend = 0.04). Among premenopausal women, carriers of the Ser allele had (not significantly) greater density (versus Gly/Gly genotype: +7.1%; P trend = 0.07). In addition, among current users of hormone replacement therapy, we observed that women with the low-activity Met/Met genotype of COMT had greater breast density (versus the Val/Val genotype: +11.7%; P trend = 0.01). CONCLUSION: Additional large studies evaluating these and other candidate breast cancer genes will be required to determine what proportion, if any, of the interindividual differences in breast density are due to underlying genetic variation in genes involved in steroid hormone biosynthesis or metabolism.

Mammographic density and breast cancer after ductal carcinoma in situ.

Women with ductal carcinoma in situ (DCIS) are at substantially increased risk for a second breast cancer, but few strong predictors for these subsequent tumors have been identified. We used Cox regression modeling to examine the association between mammographic density at diagnosis of DCIS of 504 women from the National Surgical Adjuvant Breast and Bowel Project B-17 trial and risk of subsequent breast cancer events. In this group of patients, mostly 50 years old or older, approximately 6.6% had breasts categorized as highly dense (i.e., > or =75% of the breast occupied by dense tissue). After adjusting for treatment with radiotherapy, age, and body mass index, women with highly dense breasts had 2.8 (95% confidence interval [CI] = 1.3 to 6.1) times the risk of subsequent breast cancer (DCIS or invasive), 3.2 (95% CI = 1.2 to 8.5) times the risk of invasive breast cancer, and 3.0 (95% CI = 1.2 to 7.5) times the risk of any ipsilateral breast cancer, compared with women with less than 25% of the breast occupied by dense tissue. Our results provide initial evidence that the risk of second breast cancers may be increased among DCIS patients with highly dense breasts.

Secular stability and reliability of measurements of the percentage of dense tissue on mammograms.

Elevated mammographic density is associated with increased risk of breast cancer. We conducted a reliability study on mammographic density assessments to determine their potential usefulness for projecting individual breast cancer risk. We used baseline screening mammograms from 7251 women in the Breast Cancer Detection Demonstration Project (BCDDP). Repeated measurements from the same images were used to assess measurement variability by an experienced evaluator. Intraclass correlations of assessments over time usually exceeded 0.9, indicating usefulness for prospective applications. Data also indicated it may be reasonable to include cases identified in the first year of screening together with other cases in developing a risk model. Older ages and increased weight were associated with decreased mammographic density. The density of the right breast slightly exceeded that of the left. Among women who developed breast cancer, the baseline mammographic density of the ipsilateral (diseased) breast was 0.53 (95% confidence interval (CI) 0.20-0.86) percentage units higher than in the contralateral breast.