Longitudinal Association of Quantitative Background Parenchymal Enhancement with Breast Cancer Risk among Women with BRCA1/2 Pathogenic Variants

BACKGROUND: Background parenchymal enhancement (BPE) on breast MRI is a potential biomarker for breast cancer risk, but its utility among women with BRCA1/2 pathogenic variants (PV) is unclear. METHODS: We investigated the longitudinal association of quantitative BPE measures with breast cancer risk among women with BRCA1/2 PVs. Measures were median BPE, and the proportion of fibroglandular tissue (FGT) voxels with ≥20% enhancement (BPE20/FGT). Primary outcome was incident breast cancer diagnosed ≥6 months after MRI. Repeated measures proportional hazards models assessed associations of BPE with cancer, adjusting for age, menopausal status, volumetric breast density (VBD), body mass index (BMI), and BRCA type. RESULTS: Among 385 women - 39 of whom developed breast cancer - with 1,278 MRIs, median age at first MRI was 36 (IQR 30-46) years. BPE20/FGT ratio was associated with increased risk in both the smaller model (age and menopause adjusted, HR=1.13, p<0.005) and the larger (adjusted for VBD, BMI, and BRCA1 versus BRCA2, HR=1.13, p<0.005, both measures HR per 10 units). Association was stronger in axial MRIs in both models (smaller: HR=1.26, p<0.001; larger: HR=1.34, p<0.005). Median BPE showed similar results. In a subset of 165 women, BPE decrease was observed from last measurement pre-oophorectomy to first post-oophorectomy (p<0.04). CONCLUSIONS: In this study, higher BPE is associated with increased breast cancer risk in women with BRCA1/2 PVs, and BPE decreases post-oophorectomy. IMPACT: Quantitative BPE may help better evaluate breast cancer risk for women with BRCA1/2 PVs, helping women balance the risks and benefits of risk-reducing interventions.