Abstract PS3-07-22: Correlation between MRI background parenchymal enhancement and serum estradiol in premenopausal patients on neoadjuvant endocrine therapy for breast cancer

Abstract Purpose Background parenchymal enhancement (BPE), the contrast enhancement of normal fibroglandular tissue on dynamic contrast-enhanced breast MRI, is hormonally dependent and fluctuates with the menstrual cycle, lactation, and pregnancy. In patients with breast cancer, both endocrine therapy and chemotherapy can decrease BPE levels during treatment. Notably, a lack of BPE suppression was associated with inferior response after neoadjuvant chemotherapy in hormone receptor-positive (HR+) cancer. In HR+ breast cancer, BPE may be particularly relevant as estrogen fuels the tumor’s growth. However, there is limited clinical research directly comparing BPE and serum estradiol levels. This study aimed to investigate 1) the correlation between BPE and serum estradiol levels in treatment-naïve premenopausal patients with HR+ breast cancer and 2) the association between BPE suppression and serum estradiol suppression during neoadjuvant endocrine therapy (NET). Methods We retrospectively reviewed data from premenopausal patients enrolled in the Endocrine Optimization Pilot (EOP), a sub-study of the I-SPY 2 TRIAL, which tests new endocrine strategies in patients with stage 2/3, MammaPrint (MP) low-risk (index 0 to 1), HR+/HER2-negative (HER2-) breast cancer. Patients with MP High1 (index -0.57 to 0) tumors were eligible if clinically node negative. This study included 58 EOP patients who had both serial serum estradiol levels (drawn monthly) and BPE data available. These patients started ovarian function suppression (OFS) at various times based on their assigned treatment regimen: before NET start, n=28; at cycle 1, n=16; at cycle 2, n=14. The average estradiol levels over six months on NET were categorized into two groups: suppressed to the postmenopausal range (<10 pg/mL) or non-suppressed (≥10 pg/mL). MRI scans at baseline (before NET) and pre-surgery (after six months of NET) were analyzed. BPE was calculated on the contralateral breast as the mean early (∼150s post-contrast injection) percent enhancement of the central 50% of the axial slices. The Spearman’s correlation coefficient and the Wilcoxon rank-sum test were used to examine the relationship between BPE and estradiol. Results Treatment-naïve estradiol levels were available for 25 of the 58 patients, with the median [1st, 3rd quartile] of 82.7 [32.4, 250] pg/mL. A positive correlation was observed between treatment-naïve estradiol and baseline BPE, with a correlation coefficient of ρ = 0.74 (p < 10-5). There was no significant difference in the treatment-naïve estradiol levels between patients who later showed estradiol suppression to the menopausal range during NET (n=14 [56 %]) and those who did not (n=11 [44 %]) (81.3 pg/mL versus 86.5 pg/mL, respectively (p=0.39)). During NET, estradiol levels were suppressed to the postmenopausal range in 26 of the 58 patients (45%). Estradiol suppression was significantly associated with greater reduction in post-treatment BPE: -42.7% [-54.3, -21.8] BPE reduction for the suppressed estradiol group versus -15.0% [-40.6, 6.85] for the non-suppressed estradiol group (p=0.002). Conclusion This study demonstrates the estrogen dependency of BPE in premenopausal patients with HR+/HER2- breast cancer. Baseline estradiol levels positively correlated with baseline BPE, and the suppression of on-treatment estradiol was associated with greater BPE suppression following NET. Our findings further support exploration of the use of BPE as a reflection of estradiol level under NET and OFS in addition to other MRI biomarkers such as functional tumor volume. These complementary imaging biomarkers could independently reflect both non-malignant and tumor-specific biological processes to improve predicted performance. Citation Format: S. Choi, N. Onishi, P. Metanat, R. Mukhtar, K. Giridhar, M. P. Goetz, L. Huppert, A. Elias, O. Olopade, I-SPY2 Imaging Working Group, I-SPY2 Investigator Network, L. Esserman, J. Chien, N. Hylton. Correlation between MRI background parenchymal enhancement and serum estradiol in premenopausal patients on neoadjuvant endocrine therapy for breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-07-22.