BMC Cancer Research article Mammographic density and epithelial histopathologic markers Martijn Verheus1, Gertraud Maskarinec*1, Eva Erber1, Jana S Steude1, Jeffrey Killeen1,3, Brenda Y Hernandez1 and J Mark Cline2 BioMed Central Open Access Address: 1Cancer Research Center, University of Hawaii, Honolulu, Hawaii, USA, 2Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA and 3Kapiolani Medical Center for Women and Children, Honolulu, Hawaii, USA Email: Martijn Verheus - m.verheus@nki.nl; Gertraud Maskarinec* - gertraud@crch.hawaii.edu; Eva Erber - eerber@crch.hawaii.edu; Jana S Steude - janasofias@yahoo.com; Jeffrey Killeen - jeffrey.killeen@hawaiilabs.com; Brenda Y Hernandez - brenda@crch.hawaii.edu; J Mark Cline - jmcline@wfubmc.edu * Corresponding author Published: 13 June 2009 BMC Cancer 2009, 9:182 doi:10.1186/1471-2407-9-182 This article is available from: http://www.biomedcentral.com/1471-2407/9/182 Received: 6 January 2009 Accepted: 13 June 2009 © 2009 Verheus et al., licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: We explored the association of mammographic density, a breast cancer risk factor, with hormonal and proliferation markers in benign tissue from tumor blocks of pre-and postmenopausal breast cancer cases. Methods: Breast cancer cases were recruited from a case-control study on breast density. Mammographic density was assessed on digitized prediagnostic mammograms using a computer- assisted method. For 279 participants of the original study, we obtained tumor blocks and prepared tissue microarrays (TMA), but benign tissue cores were only available for 159 women. The TMAs were immunostained for estrogen receptor alpha (ERα) and beta (ERβ), progesterone receptor (PR), HER2/neu, Ki-67, and Proliferating Cell Nuclear Antigen (PCNA). We applied general linear models to compute breast density according to marker expression. Results: A substantial proportion of the samples were in the low or no staining categories. None of the results was statistically significant, but women with PR and ERβ staining had 3.4% and 2.4% higher percent density. The respective values for Caucasians were 5.7% and 11.6% but less in Japanese women (3.5% and -1.1%). Percent density was 3.4% higher in women with any Ki-67 staining and 2.2% in those with positive PCNA staining. Conclusion: This study detected little evidence for an association between mammographic density and expression of steroid receptors and proliferation markers in breast tissue, but it illustrated the problems of locating tumor blocks and benign breast tissue samples for epidemiologic research. Given the suggestive findings, future studies examining estrogen effects in tissue, cell proliferation, and density in the breast may be informative. Background Although a vast body of literature describes a positive association between mammographic density and breast cancer risk with an estimated relative risk of 4 or higher for women in the highest as compared to the lowest density category [1], not much is known about the underlying his- topathology of breast density [2]. Such knowledge may contribute to breast cancer prevention because it may Page 1 of 8 (page number not for citation purposes)