Introduction: The mammographic density (MD), which is the reflection of the proportion of the fibrogladular tissue in breast, is a well-known risk factor for breast cancer development. Recent studies have suggested that MD can also increase the risk of ipsilateral breast tumor recurrence (IBTR) and contralateral breast cancer (CBC) development. However, the data regarding the role of MD on IBTR and CBC is conflicting. To address this issue, we aimed to investigate the relationship between MD and IBTR and CBC in a large cohort of patients treated in a single institution to minimize the heterogeneity of MD assessment and breast cancer treatments.Methods: In this study, we retrospectively reviewed the MD data for 9,011 female breast cancer patients who underwent unilateral breast conserving surgeries between January 2000 and and December 2018 at Seoul National University Hospital. This study was approved by the Institutional Review Board of Seoul National University Hospital (IRB No: 2107-002-1231). The baseline MD for each patient was determined by the digital mammography image obtained within one year since the time of diagnosis. The patients were classified into 'high MD' or 'low MD' based on their baseline MD according to the 5th edition BI-RADS recommendation from the American College of Radiology. Results:The median age of the patients is 49.3 (19-88). Among the 9,011 patients, 6,440 (71.5%) were classified as 'high density' according to their baseline MD. The median follow-up duration was 75.2 months.The cumulative incidence of IBTR in our patient cohort was 2.1% at 10 years. The 'high MD' group experienced more incidences of IBTR with the hazard ratio of 1.44 (95% C.I., 1.07-1.95). Age at the time of diagnosis was also shown to be a significant prognostic factor for IBTR (p<0.001, HR, 0.95; 95%CI, 0.94 - 0.97) and the younger age was significantly associated with high MD (p<0.001). To adjust for the effect of age on IBTR, we stratified the patients according to their age at diagnosis. When the patients were stratified at their median age, the MD did not show significant effect on the development of IBTR. Cox regression analysis also revealed that the degree of MD does not independently predict the risk of IBTR development.For CBC, the cumulative rate at 5 year was 1.4%. Similar to the IBTR, high MD group and young age were significantly risk factors of developing CBC. However, the prognostic impact of high MD was more evident in patients of less than 50 years old. Furthermore, unlike the IBTR, the MD group remained to be independent predictor of CBC after adjusting for other prognostic factors. Conclusion:The degree of MD did not independently predict the risk of IBTR in patients undergoing breast conserving surgery. However, high MD was significantly associated with increased risk of developing CBC especially in younger breast cancer patients.

Citation Format: Jong Ho Cheun, Hong-Kyu Kim, Han-Byoel Lee, Wonshik Han, Hyeong-Gon Moon. Mammographic density is associated with increased risk of contralateral breast cancers but not of ipsilateral breast tumor recurrences [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-07.