BMC Cancer 2009, 9:182 http://www.biomedcentral.com/1471-2407/9/182 Table 1: Characteristics of women recruited for the TMA study and the original study* Original study TMA study Variable Sample size (N) Ethnicity (%) Caucasian Hawaiian Japanese Other Age at mammogram Body mass index (m/kg2) Family history of breast cancer (%) Age at menarche (%) < 13 years 13–14 years >14 years Number of children (%) 0–1 2 to 3 >3 Age at first live birth (%) <21 years 21–30 years >30 years HT use at mammogram (%) No use Estrogen only Estrogen plus progestogen Breast measures Total breast area Breast density in percent Absolute density Menopausal Status (%) Premenopausal Postmenopausal 607 185 (30.5) 80 (13.2) 287 (47.3) 55 (9.1) 62.1 ± 8.5 25.1 ± 5.1 104 (17.1) 324 (54.4) 217 (36.4) 55 (9.2) 172 (28.3) 312 (51.4) 123 (20.3) 80 (13.6) 359 (61.0) 56 (9.5) 94 (16.0) 264 (43.5) 174 (28.7) 169 (27.8) 117.9 ± 58.1 35.3 ± 23.3 35.9 ± 27.0 152 (25.0) 455 (75.0) 159 49 (30.8) 21 (13.2) 70 (44.0) 19 (12.0) 59.8 ± 8.7 24.4 ± 4.3 17 (10.7) 86 (54.1) 58 (36.5) 15 (9.4) 43 (27.0) 86 (54.1) 30 (18.9) 21 (13.2) 102 (64.2) 11 (6.9) 25 (15.7) 64 (40.3) 46 (28.9) 49 (30.8) 110 ± 52.9 38.4 ± 24.8 39.5 ± 23.4 60 (37.7) 99 (62.3) * Means ± standard deviation unless stated otherwise highest in Caucasian women and in the subgroup of women with other ethnicities (43 cm2) and lower in Hawaiian (36 cm2) and Japanese women (34 cm2). Per- cent mammographic density was highest among the sub- group of women with other ethnicities (50%) and lowest in Hawaiian women (30%), while it was intermediate in Japanese (40%) and Caucasians (38%). A substantial proportion of the samples were in the low or no staining categories (Table 2). The percentages were 88%, 70%, 49%, 67%, 42%, and 60% for ERα, ERβ, PR, HER2, PCNA, and Ki-67, respectively. A similar propor- tion of Japanese and Caucasian women were in the high- est staining category for all markers; none of the differences was statistically significant. The sample size was too small to examine other ethnic groups. Small dif- ferences in breast density were seen between staining cat- egories of several markers, but, with two exceptions in the subgroup of Caucasians, none of the results were statisti- cally significant. Percent density was higher in the overall and stratified analyses for subjects with PR staining (all women: 3.4%; Caucasian: 5.8%; Japanese: 3.5%). In women with higher ERβ staining, percent density was higher in the total population and in Caucasians (2.4% and 11.6%) but not in Japanese. No associations of per- cent density with ERα and HER2/neu were observed. Per- cent density was somewhat higher in women with Ki-67 staining, both in the total population (3.4%) and in Cau- casians (3.8%) and Japanese (4.4%). Positive PCNA stain- ing showed slightly higher percent density in all women and in Japanese but not in Caucasians. As an exploratory analysis, we stratified by total breast area to capture possible effects due to high adiposity. More women with large breasts had PR expression than women with small breasts (58% vs. 44%, p = 0.08) (Table 3). The opposite was seen for ER expression (ERα: 62% vs. 77%, p = 0.44; ERβ: 56% vs. 65%, p = 0.30). Women with large breasts and positive staining for all markers, except Ki-67, had higher percent densities, especially for PR (6.2%), ERβ (6.4%), and PCNA (4%). Although not sta- tistically significant, women with small breasts who stained for hormonal markers showed slightly lower per- cent density except for PR with 4.3% higher density in cat- egory 2. Those with positive Ki-67 staining had 4.4% higher density, whereas positive staining for PCNA made no difference among women with small breasts. With few exceptions, the associations with absolute area were simi- lar to the findings with percent density. Restricting the analyses to postmenopausal women did not change the results; no significant associations were observed (data not shown). Discussion This investigation of breast density and immunohisto- chemical marker expression in TMAs observed no signifi- cant associations in the entire study population, but it appeared that mammographic density was slightly higher for women with PR expression as compared to those with no PR expression. This observation was consistent across the two major ethnic groups and women with different breast sizes. The difference between low and high catego- ries was 3–4% in density which, if a true finding, may translate into a 6–8% higher breast cancer risk [33]. Only in women with large breasts, mammographic density was slightly higher in subjects with ERα, ERβ, and HER2 expression, but again, the results were not statistically sig- nificant. For category 2 expression of Ki-67 and PCNA, percent breast density was slightly higher in the entire population. The findings in Caucasians who, on average, have larger breasts than Japanese largely reflected the results in the subgroup of women with large breasts, whereas the findings in Japanese women tended to be closer to the results of women with small breasts. The Page 4 of 8 (page number not for citation purposes)