Abstract P2-04-04: Association of mammographic density and molecular breast cancer subtype
Authors: Edwards Brandy L , Atkins Kristen A , Stukenborg George J , Novicoff Wendy M , Larson Krista N , Cohn Wendy F , Harvey Jennifer A , Schroen Anneke T 
Published: May 2015

Background: While mammographic density is linked to increased breast cancer risk, limited yet conflicting data exists on an association between density and developing specific molecular subtypes of breast cancer.

Methods: Eligible patients were enrolled in a larger study on breast density, diagnosed with cancer between 2003-2013, and had pathology and films available for review. Density was classified qualitatively from existing radiology reports according to Breast Imaging Reporting and Data System (BIRADS) classification and quantitatively by volumetric breast density measurements using Volpara SolutionsTM software. Subtype was assigned by hormone receptor status, tumor grade and mitotic score (MS). Subtype categories included: Luminal A (ER/PR + & grade 1; ER/PR + & grade 2 & MS=1; ER+/PR- & grade 1); Luminal B (ER+ & grade 3 or MS=3; ER+/PR- & grade 2; ER/PR + & grade 2 & MS=2); Her-2 + (ER+ or ER - & Her-2 +); Triple Negative (ER/PR-, Her-2 -). Relevant pre-cancer factors including patient age, race, BMI, family history of breast cancer, and biopsy showing LCIS were included in analysis.

Results: Of 604 patients with invasive cancer, 457 had sufficient information for analysis. Among these, 233 (51%) had Luminal A, 79 (17%) Luminal B, 59 (13%) Her-2 +, and 86 (19%) Triple Negative tumors. Younger women and those with denser breasts based on quantitative measurements were more likely to have Her-2+ tumors (Table 1); this association was not seen using the standard BIRADS classification. Triple Negative tumors were less common in patients with LCIS and more common in African Americans. A multinomial logistic regression model controlling for pre-cancer patient factors demonstrated that while quantitative breast density does not significantly differentiate between all molecular subtypes (p=0.140), the association between Her-2+ tumors and denser breasts using continuous quantitative measurements is significant (p=0.035).

Conclusion: Women with denser breasts by continuous-scaled quantitative measurements are at higher risk for Her-2+ tumors; an association not delineated using standard BIRADS density classification. Delineating risk factors specific to molecular breast cancer subtype may promote individualized risk prediction models and prevention strategies.

Table 1. Association between patient factors and molecular breast cancer subtype Molecular SubtypeVariableLuminal ALuminal BHer-2+Triple NegativeP value (n=233)(n=79)(n=59)(n=86) Age (median,IQR)61 (54,70)58 (50,67)54 (46,70)59 (48,67)0.006BMI (median,IQR)27.1 (22.9,30.5)25.7 (23.0,30.0)26.0 (22.7,32.6)28.1 (24.3,32.6)0.173Volpara density (median,IQR)7.18 (4.74,11.25)8.68 (5.68,14.34)10.25 (5.96,16.51)7.00 (4.97,11.89)0.002BIRADS density (n,%)0.183 Fatty42 (18.0%)15 (19.0%)5 (8.5%)16 (18.6%)  Scattered103 (44.2%)27 (34.2%)20 (33.9%)36 (41.9%)  Heterogeneous74 (31.8%)30 (38.0%)25 (42.4%)26 *30.2%)  Extreme14 (6.0%)6 (7.6%)9 (15.2%)7 (8.1%)  Unspecified01 (1.2%)01 (1.2%) Race (n,%)0.002 Caucasian202 (86.7%)65 (82.3%)51 (86.4%)61 (70.9%)  African American23 (9.9%)13 (16.5%)6 (10.2%)23 (26.7%)  Other2 (0.9%)02 (3.4%)0  Unspecified6 (2.6%)1 (1.2%)02 (2.3%) LCIS (n,%)48 (20.6%)8 (10.1%)8 (13.6%)5 (5.8%)0.004Family history of breast cancer (n,%)107 (45.9%)34 (43.0%)21 (35.6%)39 (45.35%)0.625

Citation Format: Brandy L Edwards, Kristen A Atkins, George J Stukenborg, Wendy M Novicoff, Krista N Larson, Wendy F Cohn, Jennifer A Harvey, Anneke T Schroen. Association of mammographic density and molecular breast cancer subtype [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 P2-04-04.