Purpose: Mammographic density is one of the strongest risk factors for breast cancer. However, very little is known about how other breast cancer risk factors may modify the association between breast density and breast cancer. We investigated if associations of breast density and breast cancer differ according to the level of other known breast cancer risk factors.
Methods: This study included 1,044 incident breast cancer cases diagnosed within the Nurses' Health Study cohort and 1,794 matched controls. Percent breast density, absolute dense and non-dense areas were measured from digitized film images with computer-assisted methods. Information on breast cancer risk factors was obtained prospectively from biennial questionnaires completed before the date of the cancer diagnosis for cancer cases and their matched controls. We used multivariate logistic regression to describe the association between breast density measures and breast cancer risk. The risk estimates were presented as odds ratios (ORs) and their corresponding 95% Confidence Intervals (95% CIs). To assess if the association between breast density and breast cancer risk was significantly different according to the levels of known risk factors, we conducted statistical tests of interaction by using respective medians within each category of the variables that were continuous in nature (alcohol consumption, age at menarche, age at menopause BMI, physical activity, and density measures) to model interactions. To test interactions of parity/age at first child's birth with density, parity/age at first child's birth was treated as an ordinal variable. Interactions of parity and age at first child's birth were also investigated separately in a secondary analysis restricted to parous women.
Results: Percent breast density and absolute non-dense area were more strongly associated with breast cancer risk in current postmenopausal hormone users as compared to women with past or no hormone use history (percent density≥50% vs.10%: OR=5.34 [95% CI: 3.36-8.49], OR=2.69 [95% CI: 1.32-5.49], OR=2.57 [95% CI: 1.18-5.60], respectively, p for interaction=0.04; non-dense area 4th vs.1st quartile: OR=0.42 [95% CI: 0.30-0.61], OR=0.50 [95% CI: 0.28-0.92], OR=0.72 [95% CI: 0.41-1.29], respectively, p for interaction =0.04). Associations of percent density with breast cancer risk were stronger in parous women with younger age at first child's birth, as compared to women with age at first child's birth>25 years or nulliparous women (percent density ≥50% vs.10%: OR=4.11 [95% CI: 2.54-6.66], OR=3.29 [95% CI: 2.05-5.29], and OR=2.30 [95% CI: 0.61-8.73], respectively, p for interaction=0.02). However, when the analysis was restricted to parous women, there were no significant interactions of either parity or age at first child's birth alone with percent density, absolute dense and non-dense area on the risk of breast cancer (p for interaction>0.05). The associations of density with breast cancer risk did not differ by the levels of body mass index, age at menarche, age at menopause, alcohol consumption, a family history of breast cancer, a personal history of benign breast disease, and physical activity.
Conclusions: Women with dense breasts who currently use postmenopausal hormone therapy are at a particularly high risk of breast cancer.
Citation Format: Lusine Yaghjyan, Graham Colditz, Bernard Rosner, Rulla Tamimi. Mammographic breast density and breast cancer risk: Interactions of percent density, absolute dense and non-dense areas with breast cancer risk factors. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A51.