Background: Dynamic contrast-enhanced MRI (DCE-MRI) plays a crucial role in breast cancer detection and monitoring of therapeutic response by assessing the tumor vascular network. The MRI contrast agent enhances not only tumor tissue, but also normal breast tissue, a phenomena known as background parenchymal enhancement (BPE). The degree of BPE can be variable between different individuals, is influenced by the hormonal milieu, and displays variable anatomical and kinetic patterns. Changes in BPE intensity over the course of neoadjuvant therapy (NAT) have been found to correlate with response to therapy in both the ipsilateral and contralateral breast. The present study assesses changes in the rate of BPE over the course of NAT to predict eventual response to NAT. Importantly, this study was conducted in collaboration with community-care centers (i.e., not research-oriented medical centers). Methods: Women with locally advanced breast cancer (N = 19) were imaged four times during the course of NAT: 1) prior to the start of NAT, 2) after 1 cycle of NAT, 3) after 2-4 cycles of NAT, and 4) 1 cycle after MRI #3. Imaging data was acquired on 3T Siemens Skyra scanners equipped with a 8- or 16-channel breast coils. Gadolinium-based contrast agent (0.1 mmol/kg of Multihance or 10 mL of Gadovist) was administered intravenously at 2 mL/sec after the acquisition of baseline scans. DCE-MRI data was collected in 10 sagittal slices with a temporal resolution of 7.27 sec for a total acquisition time of eight minutes. The tumor was semi-automatically segmented using a manually drawn region of interest (ROI) followed by fuzzy c-means clustering of a post-contrast high-resolution anatomical scan. Fibroglandular parenchyma was segmented from adipose tissue using fuzzy c-means clustering and further segmented into three concentric rings at prescribed radial distances from the tumor boundary. Enhancement time courses were temporally smoothed using a moving average filter of width 5 and normalized to baseline intensity to yield relative enhancement time courses. The enhancement slope, defined as the slope of the curve at half maximal intensity, was calculated from the kinetic uptake curve for the tumor, adipose, and concentric rings of fibroglandular tissue surrounding the tumor. Results: Prior to commencing NAT, women with faster tumoral enhancement had faster fibroglandular enhancement (r = 0.62, p < 0.05). There was no correlation between tumor and adipose enhancement rate or fibroglandular and adipose enhancement rate. Among concentric rings of fibroglandular tissue, the tissue most distal to the tumor enhanced faster than tissue more proximal to the tumor (p < 0.05). Over the course of NAT, the rate of fibroglandular enhancement tended to slow (p < 0.01). Women who ultimately achieved pathological complete response (pCR; n = 6) displayed a faster rate of fibroglandular enhancement at the 4th MRI than women with residual tumor at the time of resection (n = 13). This correlation was preserved (p < 0.01) in a subset of patients who received AC◊T therapy, the most common treatment arm in this study (n = 4 pCR, n = 8 non-pCR). Furthermore, this relationship persisted when the fibroglandular enhancement rate was normalized by the tumoral enhancement rate in both the full patient cohort and in the 12 patients who received AC◊T (p < 0.05, both cohorts). Conclusions: These results demonstrate that the rate of fibroglandular tissue enhancement in patients receiving NAT for breast cancer reflects response to therapy. The increased rate of fibroglandular enhancement in women achieving pCR may reflect treatment-mediated vascular remodeling in healthy breast tissue. Incorporating quantitative characterization of parenchymal enhancement kinetics into treatment response models warrants further investigation.

Citation Format: John Virostko, Erin M Higgins, Chengyue Wu, Anna G Sorace, Debra Patt, Boone Goodgame, Thomas E Yankeelov. The rate of parenchymal enhancement during DCE-MRI reflects response to neoadjuvant therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD9-07.