Abstract P4-04-11: Comparing tissue compositions of within-individual mammographically high and low dense breast tissue

Abstract

Abstract Abstract Purpose Mammographic density (MD) refers to the extent of radio-opaque breast tissue on a mammogram. Adjusted for a women’s age and body mass index (BMI), it is a strong and independent risk factor for breast cancer (BC). The presentation of mammographically dense breast is not uncommon in the normal female population, and patients’ awareness of its association with BC risk has been growing following mandatory reporting of MD by physicians in several states of America. Women with breasts that have over 75% dense tissue are 4 to 6 times more likely to develop BC than women with breasts that have less than 10% dense tissue. However, the biological basis of how high MD raises BC risk remains elusive. We aimed to examine the histological and molecular differences between high and low dense breast tissues of healthy women, using specimens accrued from prophylactic mastectomy procedures. Method 48 women between 2008 and 2013 underwent prophylactic mastectomy at St Vincent’s Hospital and Peter MacCallum Cancer Centre due to a high BC risk profile. Of these, 41 were eligible for analyses. Tissue slice resected from the mastectomy specimen was X-rayed, and high (HD) and low dense (LD) regions were dissected based on the radiological appearance. The histological composition, immunohistochemistry and proliferation status were assessed on matched high and low MD tissue of the same breast. Signed rank test and paired t test were used for quantitative analyses of potential differences between HD and LD tissue. Result HD tissue demonstrated a significantly greater proportion of stroma (p<0.0001) and epithelium (p<0.0001), and less amount of fat (p<0.0001) than LD tissue (n=41 women). Epithelium from HD region also demonstrated epithelial-mesenchymal transition (EMT) plasticity, which was evident as the co-expression of cytokeratin (CK)-19 and vimentin in the glandular area. There was no significant difference with regards to oestrogen receptor (ER) (p= 0.2772), progesterone receptor (PR) (p= 0.9910), and Ki-67 (p= 0.6028) expression between HD and LD tissue. Conclusion and Significance We found that increased stroma and epithelium proportions contribute to the dense appearance on mammogram. Moreover, dense tissue did not demonstrate differed hormonal receptor expression or proliferation status from non-dense tissue, but showed a preponderance of EMT in the form of co-localisation by both CK-19 and vimentin in some of the epithelial cells. Our study is the first to report EMT phenomenon in benign mammary tissue, and suggests that investigations of the stromal micro-environment, and their interactions with epithelium may be key to improving our understanding on MD-mediated BC risk. Citation Format: Cecilia W Huo, Dexing Huang, Grace L Chew, Prue Hill, Wendy V Ingman, Michael Henderson, Kara L Britt, Rik Thompson. Comparing tissue compositions of within-individual mammographically high and low dense breast tissue [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-11.