BMC Cancer 2009, 9:182 http://www.biomedcentral.com/1471-2407/9/182 predominantly fatty breast tissue and different mammo- study design. All authors read and approved the final graphic patterns [44]. Conclusion This investigation illustrates the problems of obtaining benign breast tissue samples for a representative sample of participants in epidemiologic studies. To benefit from the advantages of the TMA technique in future research, it is recommended to select the areas for taking the tissue cores carefully and to minimize the loss of specimens during immunostaining. Based on our few suggestive findings, future mammographic density investigations may pursue estrogenic effects as assessed by PR and cell proliferation using Ki67 and other such markers to examine the ques- tion of local estrogen activity in relation to breast density. The slightly higher breast density with PR expression sug- gests a stronger estrogenic response in mammographically dense breasts possibly leading to stronger cell prolifera- tion, an idea supported by associations of breast density with hyperplasia and other benign breast pathology [8,10,45,46]. Although not statistically significant, the higher breast density with steroid receptor expression in women with large breasts as compared to women with small breasts indicates a role of locally produced estrogens in women with more adipose tissue [40]. On the other hand, it is most likely that chance was responsible for the small differences observed in this exploratory study. Given the weak associations in the current investigations and the discrepant findings across studies, the roles of growth factors and the properties of the stromal matrix in shaping breast density also deserve further attention [4,9,12]. List of abbreviations BMI: Body mass index; CI: Confidence interval; ER: Estro- gen receptor; HT: Hormone therapy; HTR: Hawaii tumor registry; ICC: Intraclass correlation coefficient; MEC: Mul- tiethnic cohort; NAF: Nipple aspirate fluid; NCC: Nested case control study; PCNA: Proliferating Cell Nuclear Anti- gen; PR: Progesterone receptor; TMA: Tissue microarray. Competing interests The authors declare that they have no competing interests. Authors' contributions MV carried out the statistical analysis and drafted the manuscript. GM conceived of the study, obtained fund- ing, and directed the statistical analysis. EE participated in the design and the data collection and contributed to the statistical analysis. JSS contributed to the data collection and the statistical analysis. JK evaluated and selected the pathologic specimens and provided input on pathologic issues. BH provided access to the pathologic specimens and contributed to the study design. 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