Marker ERα ERβ PR HER2/neu Ki-67 PCNA BMC Cancer 2009, 9:182 http://www.biomedcentral.com/1471-2407/9/182 Table 2: Marker expression and mammographic density by ethnicity All women (n = 159) Caucasian (n = 49) Japanese (n = 70) Category* 1 2 P-value Category Category P-value % density† Dense area# Number % density Dense area Number % density Dense area Number % density Dense area Number % density Dense area Number % density Dense area Number 36.9 33.7 122 35.8 33.0 110 34.9 30.6 77 37.1 34.4 104 34.3 32.9 65 36.0 33.4 95 35.6 33.6 35 38.2 34.6 47 38.3 36.4 81 36.3 33.2 52 37.7 33.5 90 38.2 33.7 63 0.75 0.98 0.49 0.66 0.28 0.09 0.82 0.74 0.32 0.87 0.50 0.94 1 39.8 38.2 38 33.8 34.4 36 35.3 31.1 23 35.7 36.4 34 35.5 38.7 16 37.7 36.7 28 2 23.9 26.2 11 45.4 40.9 13 41.0 45.9 25 40.9 36.5 15 39.3 34.9 32 37.1 36.4 20 0.04 0.18 0.05 0.38 0.30 0.03 0.38 0.99 0.53 0.60 0.91 0.97 1 38.8 33.8 53 40.2 35.2 47 37.5 35.2 35 41.3 35.5 45 36.8 32.8 31 38.7 35.1 42 2 44.5 38.0 16 39.1 33.3 21 41.0 34.4 35 37.9 33.6 23 41.2 35.3 39 42.2 33.9 28 P-value 0.39 0.50 0.85 0.74 0.57 0.90 0.57 0.73 0.46 0.66 0.52 0.82 * Categories for ERα, ERβ, HER2/neu and PCNA; category 1 <10% staining, category 2 ≥ 10% staining. Categories for PR and Ki-67; category 1 = no staining, category 2 = any staining † Mean percent breast density # Mean dense area in cm2 Mean values and p-values calculated using general linear models adjusted for age at mammogram, BMI, ethnicity, HT use at mammogram, menopausal status, parity, age at first live birth, age at menarche and family history of breast cancer. (ERα = estrogen receptor alpha; ERβ = estrogen receptor beta; PR = progesterone receptor; HER2/neu = Human Epidermal growth factor receptor2; PCNA = Proliferating Cell Nuclear Antigen; BMI = body mass index) higher percent density among women with Japanese ancestry despite their lower breast cancer risk was also observed in the original study [33]. It is due to the small breast sizes that result in a higher percent of the breast occupied by dense tissue. As shown in cross-sectional comparisons, the size of the dense area appears to be a better indicator of risk when different ethnic groups are compared [38,39]. Six previous reports examined the underlying histological markers for breast density; one study used forensic breast samples [11], one examined reduction mammoplasty samples [5], one collected fine needle biopsies [13], two used tissues surrounding non-cancerous breast lesions [9,12], and another one identified non-cancerous tissue from mastectomy specimens [14]. Of these six studies, only one study assessed ERα and PR expression and did not find an association, but the sample size was only 56 [14]. Three studies looked at Ki-67 expression; one found no association with mammographic density [13], one found a positive association [14], and one described less proliferation in dense areas [5]. As far as we know, no pre- vious results for ERβ, HER2/neu, and PCNA have been reported. The observation that in women with small breasts, per- cent density was slightly lower for those with higher ER expression, whereas it was higher in women with large breasts and positive ER expression suggests that a possible effect of ER expression on breast density, if it exists, may depend on the amount of local estrogens. Apart from ovarian production, estrogens are metabolized from androgens in adipose tissue [40]. Thus, in women with large breasts, tissue estrogen levels would also be higher due to the larger amount of fat tissue. This idea agrees with a report that women with a nipple aspirate fluid (NAF) phenotype characterized by higher BMI and percentage body fat had higher NAF estrogen levels [41]. Therefore, Page 5 of 8 (page number not for citation purposes)