Background: Breast cancer (BC) exists as several heterogeneous subtypes with differing distributions, risk factors, tumor behaviors and clinical outcomes. The risk factors that are associated with and the clinicopathological features distinguishing BC subtypes remain undefined. In this study, we examined associations between BC risk factors and tumor clinicopathological features, and molecular subtypes of BC.

Methods: A cohort of 629 invasive BC cases from New Jersey (51.2% white; 48.8% African American [AA]) were selected from the Breast Cancer Treatment Study, who originally participated in the Women's Circle of Health Study. These women were diagnosed with stage I, II, or T3N1M0 BC between 2005 and 2010. In the present study, we examined BC risk factors (from interview-administered questionnaire data) and tumor clinicopathological features (from abstraction of detailed medical records), and their associations with BC molecular subtypes (classified by estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factors receptor 2 [HER2] expression patterns as defined in pathology records). BCs were classified into four mutually exclusive subtypes: ER+/PR+/HER2- (luminal A), ER+/PR+/HER2+, ER-/PR-/HER2+ (non-luminal HER2 expressing), and ER-/PR-/HER2- (triple negative [TN]). Multinomial logistic regression models (with luminal A as the reference group) were used to examine the associations between tumor features and BC subtype.

Results: In this study, the largest proportion of BC cases was diagnosed with luminal A (68.4%), followed by TN (14.5%), ER+/PR+/HER2+ (11.1%), and non-luminal HER2 expressing (6.0%) tumors. Younger age (<45 years) was associated with increased odds of ER+/PR+/HER2+ (Odds Ratio [OR] 2.1, 95% CI: 1.2-3.8) and TN (OR 1.7, 95% CI: 1.0-2.9) tumors. AAs were more likely to have ER+/PR+/HER2+ (OR 1.9, 95% CI: 1.1-3.1) and TN (OR 2.7, 95% CI: 1.7-4.3) tumors. Lower level of education (less than college vs. college graduate or higher: OR 1.6, 95% CI: 1.0-2.7) and lower income ($70,000 vs. ≥$70,000: OR 1.8, 95% CI: 1.1-3.2) were associated with increased odds of TN tumors. Compared to the luminal A subtype, there were increased odds of self-detection (as the mode of initial tumor detection) among ER+/PR+/HER2+ (OR 1.8, 95% CI: 1.1-3.1), non-luminal HER2 expressing (OR 2.4, 95% CI: 1.2-4.7), and TN (OR 2.7, 95% CI: 1.7-4.2) tumors. These three subtypes were also associated with poorer differentiation (ER+/PR+/HER2+, OR 3.3, 95% CI: 1.9, 5.6; non-luminal HER2 expressing, OR 16.7, 95% CI: 6.7-41.5; and TN, OR 13.8, 95% CI: 7.9-24.4); higher AJCC stage (ER+/PR+/HER2+, OR 1.9, 95% CI: 1.1, 3.2; non-luminal HER2 expressing, OR 2.6, 95% CI: 1.3-5.2; and TN, OR 1.8, 95% CI: 1.2-2.9); larger tumor size (>2.0 cm vs. ≤1.0 cm: ER+/PR+/HER2+, OR 2.5, 95% CI: 1.3-4.7; non-luminal HER2 expressing, OR 3.7, 95% CI: 1.6-8.7; and TN, OR 3.9, 95% CI: 2.1-7.5); p53 expression (ER+/PR+/HER2+, OR 2.1, 95% CI: 0.7-6.1; non-luminal HER2 expressing, OR 3.3, 95% CI: 1.0-10.4; and TN, OR 5.0, 95% CI: 2.3-10.8); and Ki67 expression (ER+/PR+/HER2+, OR 2.6, 95% CI: 1.5-4.5; non-luminal HER2 expressing, OR 2.7, 95% CI: 1.3-5.5; and TN, OR 4.2, 95% CI: 2.6-6.7) as compared to luminal A tumors.

Conclusion: These findings support an association between sociodemographics and BC subtypes, specifically showing increased odds of TN tumors among women who are younger, AA, and/or of lower socioeconomic status. These findings also suggest that the BC subtypes that are commonly observed among racial/ethnic minorities and economically disadvantaged groups exhibit more aggressive clinicopathological features and are associated with an increased likelihood of self-detection.

Citation Format: Adana A.M. Llanos, Sheenu Chandwani, Kim M. Hirshfield, Yong Lin, Elisa V. Bandera, Christine B. Ambrosone, Kitaw Demissie. Associations between clinicopathological features and breast cancer subtypes. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B47.