Abstract P3-08-05: Association of mammographic density in high risk BRCA mutated tumors compared to average risk tumors and healthy controls: Analysis of Korean Hereditary Breast and Cancer Study (KOHBRA)

Abstract

Abstract Introduction: Mammographic density is a well-known risk factor of breast cancer as a whole. Nonetheless only few studies have examined the association of density among high risk breast cancer regarding BRCA mutation. We examined mammographic density of 2019 breast cancer patients and 2029 healthy controls, regarding risk factors and BRCA mutation status. Method: Total 2019 breast cancer patients diagnosed between 1980 to 2011 were divided into two groups- high versus average risk group. Women with 1)family history of breast/ovarian cancer or 2)younger than age 40 or 3)bilateral cases were considered high risk group and were participants of ‘Korean Hereditary Breast Cancer study’ (KOHBRA) whom undergone BRCA testing. Density of 2029 healthy women who took screening mammogram during the same period were analyzed for comparison. Density was measured of the unaffected contralateral CC view using computer-assisted method Cumulus by single observer (10% randomly selected, intra-class correlation coefficient=0.96). Percent density (PD, dense area/breast area, %) among three groups, association with BRCA mutation status and breast cancer subtypes were examined. Results and Discussion: Percent density (PD) was significantly higher in high risk group compared to average risk and controls in a consecutive manner. This finding was consistent after adjusting age and BMI (p*<0.001). Mammographic percent density(PD) among three group (high risk cancer vs average risk cancer vs control)High risk cancers (N=1066)Average risk cancers (N=953)Control (N=2029)High vs AverageHigh vs controlAverage vs controlAge(yr)mean±SD41.12±9.8651.03±7.9850.52±9.090.001<0.0010.141PD (%)mean±SD52.90±12.9345.52±16.0441.52±15.80<0.001 (<0.001*)<0.001 (<0.001*)<0.001 (<0.001*)PD_median (%)<50442 (41.5%)567 (59.4%)1414 (69.7%)<0.001<0.001<0.00150≤624 (58.5%)387 (40.6%)615 (30.3%)PD_quartile (%)<2526 (2.4%)106 (11.1%)329 (16.2%)<0.001<0.001<0.00125≤ <50416 (39.0%)461 (48.3%)1085 (53.5%)50≤ <75564 (52.9%)360 (37.7%)570 (28.1%)75≤60 (5.6%)27 (2.8%)45 (2.2%)* adjusted p value by age and BMI High mammographic density showed to be a significant risk factor throughout different subtypes. Magnitude of mammographic density as a risk factor according to receptor statusTNBC (control(ref))Non-TNBCLuminalNon-Luminal25%≤PD<50% (<25%(ref))HR 4.21, 95%CI 2.12-8.38HR 1.91, 95%CI 1.50-2.43HR 1.77, 95%CI 1.38-2.26HR 3.04, 95%CI 2.00-4.6450%≤PD<75%HR 8.85, 95%CI 4.45-17.61HR 3.81, 95%CI 2.98-4.89HR 3.89, 95%C I3.03-5.00HR 5.08, 95%CI 3.32-7.8075%≤PDHR 16.25, 95%CI 6.97-37.87HR 4.09, 95%CI 2.61-6.41HR 4.09, 95%CI 2.61-6.43HR 8.16, 95%CI 4.41-15.07 Among the 1066 high risk group, 81.5% (869) undergone BRCA testing and 70(6.6%) had BRCA1, 78(7.3%) had BRCA2 mutations without significant difference in density. Similar strong magnitude association of mammographic density was observed in both BRCA mutated/non-mutated tumors and among subtypes. The ongoing GWAS and whole exome analysis of this population-subset will give insight into the tumor etiology and how density could stratify breast cancer risk for personalized screening especially in high risk population. Citation Format: Jisun Kim, Jong Won Lee, Sung Won Park, Hee Jung Shin, Hak Hee Kim, Sae-Byul Lee, Jong Han Yu, Hee Jeong Kim, Beom Seok Koh, Byung Ho Son, Sei-Hyun Ahn. Association of mammographic density in high risk BRCA mutated tumors compared to average risk tumors and healthy controls: Analysis of Korean Hereditary Breast and Cancer Study (KOHBRA) [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 P3-08-05.