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Association between Mammographic Breast Density and Breast Cancer Tumor Characteristics

¹ Group Health Cooperative, Center for Health Studies; ² Department of Epidemiology, School of Public Health and Community Medicine, University of Washington; ³ Fred Hutchinson Cancer Research Center, and ⁴ Department of Pathology, School of Medicine, University of Washington;

Requests for reprints: Erin J. Aiello, Group Health Cooperative, Center for Health Studies, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101. Phone: 206-287-2708; Fax: 206-287-2485. E-mail: aiello.e{at}ghc.org

Objective: Few studies have examined the association between breast density and breast cancer tumor characteristics. We examined the association between hormonal, proliferative, and histologic tumor characteristics and mammographic breast density in women with breast cancer.

Methods: We conducted a cross-sectional analysis in 546 women diagnosed with invasive breast cancer to evaluate the associations between breast density and tumor size, lymph node status, lymphatic or vascular invasion, histologic grade, nuclear grade, tumor differentiation, mitotic index, tumor necrosis, Ki-67 proliferation, estrogen receptor, progesterone receptor, p53, p27, cyclin E, Bcl-2, and C-erb-B2 invasion. Breast density was classified as fatty (Breast Imaging Reporting and Data System code 1 or 2; n = 373) or dense (Breast Imaging Reporting and Data System code 3 or 4; n = 173) for the cancer-free breast. A single pathologist measured all tumor markers. We examined whether the relationships were modified by interval cancer or screen-detected cancer.

Results: Women with a tumor size >1.0 cm were more likely to have dense breasts compared with women with a tumor size 1.0 cm after adjusting for confounders (odds ratio, 2.0; 95% confidence interval, 1.2-3.4 for tumor sizes 1.1-2.0 cm; odds ratio, 2.3; 95% confidence interval, 1.3-4.4 for tumor sizes 2.1-10 cm). Tumor size, lymph node status, and lymphatic or vascular invasion were positively associated with breast density among screen-detected cancers. Histologic grade and mitotic index were negatively associated with breast density in women diagnosed with an interval cancer.

Conclusions: These results suggest that breast density is related to tumor size, lymph node status, and lymphatic or vascular invasion in screen-detected cancers. Additional studies are needed to address whether these associations are due to density masking the detection of some tumors, a biological relationship, or both.

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