Abstract PO4-08-07: Background parenchymal enhancement (BPE) on breast magnetic resonance imaging as a biomarker of breast cancer risk among BRCA1/2 carriers
Authors: McCarthy Anne Marie , Nguyen Alex Anh-Tu , Mankowski Walter , Cohen Eric , Ehsan Sarah , Gillette Rhonda , Pantalone Lauren , Weinstein Susan , Conant Emily , Domchek Susan , Kontos Despina 
Published: May 2024

Abstract
Introduction: BRCA1/2 carriers are recommended to undergo dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) screening of the breasts annually. Fibroglandular tissue (FGT) may enhance with MRI contrast agent termed background parenchymal enhancement (BPE). BPE is believed to be a marker of hormonally responsive breast tissue, as BPE is impacted by aromatase inhibition and by oophorectomy. BPE has been shown to be more strongly associated with breast cancer risk than breast density. We hypothesize that BPE may serve as a useful dynamic marker of breast cancer risk among BRCA1/2 mutation carriers, given their frequent MRI screening.
Methods: We identified female BRCA1/2 carriers from the University of Pennsylvania Cancer Risk Evaluation Program with no personal history of breast or ovarian cancer at the time of breast MRI. Patients diagnosed within 6 months were excluded to remove prevalent cancer cases at MRI. Among 421 eligible patients, 42 were diagnosed with breast cancer. BPE was quantified from all available breast MRIs using a validated, fully automated method to segment fibroglandular tissue (FGT) and quantify BPE. For preprocessing, the N4ITK algorithm was used for bias-field artifact correction and FGT was segmented using a soft-margin support vector machine classifier using the T1-weighted nonfat-saturated breast MRI. FGT was segmented and quantified in 3D. For BPE quantification, the T1-weighted nonfat-saturated image and the derived FGT mask were registered to the pre-contrast DCE-MRI. The first post contrast DCE-MRI and FGT mask were used to compute the relative enhancement map compared to the pre-contrast image. We calculated BPE metrics in two ways. First, the median BPE enhancement was calculated as the median enhancement of all voxels within the FGT mask. Second the BPE enhancement ratio was calculated as the proportion of voxels enhancing at ≥20%. We performed Cox proportional hazards regression to estimate the hazard ratios for breast cancer per standard deviation unit increase in each BPE metric, with first MRI as the time origin and censoring upon bilateral mastectomy, ovarian cancer diagnosis, death, or loss to follow-up and adjustment for age at MRI, menopause status, volumetric breast density (VBD), body mass index (BMI), and BRCA1 vs. BRCA2 mutation. BPE, VBD, BMI, and menstrual status were included as time varying covariates, enabling inclusion of multiple BPE measurements per woman.
Results: The mean age at first MRI was 39 for cases and 41 for non-cases, and the mean number of MRIs was 4. There were no significant differences in median BPE (14% vs. 14%, p=0.965) or BPE ratio (34% vs. 36%, p=0.769) between cases and non-cases. In regression analyses adjusted for age and menstrual status, median BPE was significantly associated with breast cancer risk (HR=1.12, p=0.025). The HR was similar in the fully adjusted model, though did not reach statistical significance (HR=1.11, p=0.055). Higher BPE ratio was significantly associated with increased breast cancer risk in both minimally (HR=1.21, p=0.005) and fully adjusted models (HR=1.21, p=0.012).
Conclusions: Our results suggest that BPE is significantly associated with breast cancer diagnosis among BRCA1/2 carriers undergoing breast MRI screening. Both median BPE and BPE ratio metrics were associated with breast cancer risk, even after adjusting for breast density and when accounting for multiple measurements of BPE over time, suggesting that BPE may provide additional risk information for BRCA1/2 carriers.
Table 1: Results of Cox proportional hazards regression with time varying covariates
Citation Format: Anne Marie McCarthy, Alex Anh-Tu Nguyen, Walter Mankowski, Eric Cohen, Sarah Ehsan, Rhonda Gillette, Lauren Pantalone, Susan Weinstein, Emily Conant, Susan Domchek, Despina Kontos. Background parenchymal enhancement (BPE) on breast magnetic resonance imaging as a biomarker of breast cancer risk among BRCA1/2 carriers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-08-07.