Role Of Tumor Microenvironment, As Assessed By Breast Mri Background Parenchymal Enhancement (Bpe), In Modulating Response To Neoadjuvant Chemotherapy In Young Women With Localized Breast Cancer

Background: Neoadjuvant chemotherapy (NACT) is generally established as a therapeutic option for selected high-risk patients with localized breast cancer, including triple negative breast cancer (TNBC). On a patient level, achievement of pathologic complete response (pCR) at the time of surgery is associated with improved long-term outcomes and is considered to be a surrogate marker. Response to NACT is a complex phenomenon dependent on both host and tumor characteristics. While tumor characteristics, such as receptors and tumor grade, have been well studied as predictors of pCR, host characteristics to predict pCR have been less well studied. Background parenchymal enhancement (BPE) is an imaging characteristic that reflects the normal enhancement of the fibroglandular tissue on breast MRI, and could potentially modulate response to NACT by influencing the tumor microenvironment and vasculature. The aim of this study was to explore the ability of baseline BPE to predict pCR in a cohort of young women with localized breast cancer. Methods: A retrospective chart review was conducted of women ages 40 and under with stage II-III breast cancer treated with NACT at our institution from 2004 – 2014. Demographic, clinical, and pathological variables were extracted from the medical records. The primary outcome was achievement of pCR, defined as ypT0/is ypN0, after NACT. BPE pattern in the contralateral breast was obtained from pre-treatment breast MRI reports if available and otherwise was retrospectively determined by a breast radiologist blinded to patient outcomes. BPE was dichotomized as low (minimum and mild) vs. high (moderate and marked). Logistic regression was used for statistical analysis. Results: A total of 69 patients ages 40 and under received NACT for localized breast cancer during the study period and had available pre-treatment breast MRI images. Median age at diagnosis was 36 (range 27-40). The majority of patients had grade 3 (65.2%), ER+/HER2- (60.9%) tumors while 24.6% had TNBC. Among pre-treatment breast MRIs, 42 (60.9%) patients had minimum or mild BPE and 27 (39.1%) patients had moderate or marked BPE. The overall pCR rate was 39%. After controlling for tumor grade, ER status, HER2 status, clinical stage, and type of NACT, high baseline BPE was associated with a trend towards higher odds of achieving pCR compared to low BPE (OR = 1.49, 95% CI 0.47–4.71), though statistical significance was not reached (p = 0.50). When stratified by ER status, the relationship was stronger among the ER+ subset (OR 1.8, p = 0.49) compared to the ER- subset (OR 1.3, p = 0.78). Conclusions: A statistically significant association between high baseline BPE and achievement of pCR was not found in this limited sample size, but a trend towards higher pCR rates, particularly with ER+ tumors, was seen. While tumor factors have traditionally been used to predict pCR, BPE is a readily available MRI imaging characteristic that reflects the tumor microenvironment and may be useful in building a model that incorporates tumor factors along with host factors to develop personalized NACT regimens for young women with breast cancer. Citation Format: Spring L, Rutledge G, Yala A, Haddad S, Specht M, Moy B, Barzilay R, Lehman C, Bardia A. Role of tumor microenvironment, as assessed by breast MRI background parenchymal enhancement (BPE), in modulating response to neoadjuvant chemotherapy in young women with localized breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-16.