Abstract 3279: Dense and non-dense mammographic area and risk of breast cancer by age and tumor characteristics
Authors: Bertrand Kimberly A. , Scott Christopher G. , Tamimi Rulla M. , Jensen Matthew R. , Pankratz V. Shane , Norman Aaron , Shepherd John , Chen Yunn-Yi , Kerlikowske Karla , Vachon Celine M. 
Published: May 2015

Abstract
Introduction: We recently reported the percentage of mammographic density (MD) to be a breast cancer risk factor across tumor characteristics and age groups. Yet, we noted stronger associations for tumors of large size and positive lymph nodes across all ages, and ER-negative status among women ages &lt;55 years, suggesting high MD may play an important role in tumor aggressiveness, especially in younger women. We extend this initial study to investigate whether these associations with aggressive disease are due to the underlying associations of absolute dense or non-dense area, or both, with breast cancer risk.
Methods: Data were pooled from six studies including 3517 women with invasive breast cancer and 8558 without. Dense area and non-dense area were assessed from digitized film-screen mammograms using a computer-assisted threshold technique. We standardized dense and non-dense area measurements made within each study and categorized into quartiles based on the control distribution for pooled analyses. We used polytomous logistic regression to calculate breast cancer odds according to tumor type, histopathological characteristics, and receptor (ER, PR) status by age (&lt;55, 55-64, and ≥65 years), adjusting for continuous age, body mass index, and study site.
Results: Absolute dense area was associated with increased breast cancer risk [odds ratios (ORs) Q1 vs Q2: 0.67, Q3 vs Q2: 1.25, Q4 vs Q2: 1.62] and non-dense area was associated with decreased breast cancer risk (ORs: Q1 vs Q2: 1.44, Q3 vs Q2: 0.89, Q4 vs Q2: 0.71) overall and across all age groups. Positive associations for absolute dense area were observed across all invasive tumor characteristics. Stronger associations were noted for larger tumors across all ages (p-trend &lt;0.01). Among women &lt;55 years, stronger associations were observed for ER+ vs ER- [p-heterogeneity (het) = 0.02] and PR+ vs PR- tumors (p-het = 0.02). Non-dense area was inversely associated with all tumor characteristics evaluated except for tumors &lt;1.1 cm, for which no association was present. The inverse association was stronger for larger tumors, particularly for women &lt;55 years (p-trend &lt;0.01). Also among women &lt;55 years, a stronger inverse association with non-dense area was observed for ER- vs. ER+ tumors (p-het = 0.02).
Conclusion: These results suggest the strong association we previously observed of high percent MD and ER-negative disease in women &lt;55 years could be explained by the low amount of non-dense area in these women. Further research is warranted to clarify the possible differential associations of absolute dense and non-dense area on breast cancer risk according to tumor characteristics.
Citation Format: Kimberly A. Bertrand, Christopher G. Scott, Rulla M. Tamimi, Matthew R. Jensen, V. Shane Pankratz, Aaron Norman, John Shepherd, Yunn-Yi Chen, Karla Kerlikowske, Celine M. Vachon. Dense and non-dense mammographic area and risk of breast cancer by age and tumor characteristics. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3279. doi:10.1158/1538-7445.AM2014-3279