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Magnetic resonance imaging and molecular features associated with tumor-infiltrating lymphocytes in breast cancer.

ABSTRACT: BACKGROUND:We sought to investigate associations between dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) features and tumor-infiltrating lymphocytes (TILs) in breast cancer, as well as to study if MRI features are complementary to molecular markers of TILs. METHODS:In this retrospective study, we extracted 17 computational DCE-MRI features to characterize tumor and parenchyma in The Cancer Genome Atlas cohort (n?=?126). The percentage of stromal TILs was evaluated on H&E-stained histological whole-tumor sections. We first evaluated associations between individual imaging features and TILs. Multiple-hypothesis testing was corrected by the Benjamini-Hochberg method using false discovery rate (FDR). Second, we implemented LASSO (least absolute shrinkage and selection operator) and linear regression nested with tenfold cross-validation to develop an imaging signature for TILs. Next, we built a composite prediction model for TILs by combining imaging signature with molecular features. Finally, we tested the prognostic significance of the TIL model in an independent cohort (I-SPY 1; n?=?106). RESULTS:Four imaging features were significantly associated with TILs (P?

SUBMITTER: Wu J

PROVIDER: S-EPMC6122724 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Magnetic resonance imaging and molecular features associated with tumor-infiltrating lymphocytes in breast cancer.

Wu Jia J Li Xuejie X Teng Xiaodong X Rubin Daniel L DL Napel Sandy S Daniel Bruce L BL Li Ruijiang R

Breast cancer research : BCR 20180903 1

<h4>Background</h4>We sought to investigate associations between dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) features and tumor-infiltrating lymphocytes (TILs) in breast cancer, as well as to study if MRI features are complementary to molecular markers of TILs.<h4>Methods</h4>In this retrospective study, we extracted 17 computational DCE-MRI features to characterize tumor and parenchyma in The Cancer Genome Atlas cohort (n = 126). The percentage of stromal TILs was evaluated ...[more]

PMID: 30176944

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Project description:Women with germline pathogenic variants in CDH1, which encodes E-cadherin protein, are at increased lifetime risk of invasive lobular carcinoma (ILC). The associated tumor characteristics of hereditary lobular breast carcinoma (HLBC) in this high-risk population are not well-known. A single-center prospective cohort study was conducted to determine the imaging and pathologic features of HLBC compared to population-based ILC using Surveillance, Epidemiology, and End Results (SEER) data. One hundred fifty-eight women with CDH1 variants were evaluated, of whom 48 (30%) also had an ILC diagnosis. The median age at CDH1 diagnosis was 45 years [interquartile range, IQR 34-57 years] whereas the median age at diagnosis of CDH1 with concomitant ILC (HLBC) was 53 [IQR 45-62] years. Among women with HLBC, 83% (40/48) were identified with CDH1 mutation after diagnosis of ILC. Among 76 women (48%, 76/158) undergoing surveillance for ILC with breast magnetic resonance imaging (MRI), 29% (22/76) had an abnormal MRI result with available biopsy data for comparison. MRI detected ILC in 7 out of 8 biopsy-confirmed cases, corresponding with high sensitivity (88%), specificity (75%), and negative predictive value (98%); however, false-positive and false-discovery rates were elevated also (25% and 68%, respectively). HLBC was most frequently diagnosed at age 40-49 years (44%, 21/48), significantly younger than the common age of diagnosis of ILC in SEER general population data (most frequent age range 60-69 years, 28%; p < 0.001). HLBC tumors were smaller than SEER-documented ILC tumors (median 1.40 vs. 2.00 cm; p = 0.002) and had a higher incidence of background lobular carcinoma in situ (88% vs. 1%; p < 0.001) as well as progesterone receptor positivity (95% vs. 81%, p = 0.032). These findings suggest that HLBC is often detected via conventional screening methods as an early-stage hormone receptor-positive tumor, thus the clinical benefit of intensive screening with MRI may be limited to a subset of women with germline CDH1 variants.

Project description:Background: Tumor-infiltrating lymphocytes (TILs) play important roles in the prediction of prognosis and neoadjuvant therapy (NAT) efficacy in breast cancer (BRCA) patients, in this study, we identified clinicopathological factors related to BRCA TILs, then to construct and validate nomogram to predict high density of TILs. Methods: A total of 826 patients diagnosed with BRCA in Sun Yat-Sen University cancer center were enrolled in nomogram cohort. TILs were assessed using hematoxylin-eosin (H&E) staining by two pathologists. Complete clinical data were collected for analysis. Then the enrolled patients were split into a training set and validation set at a ratio of 8:2. and the backward multivariate binary logistic regression model was used to establish nomogram for predicting BRCA TILs, which were further evaluated and validated using the C-index, receiver operating characteristic (ROC) curves and calibration curves. Then another independent NAT cohort of 106 patients was established for verifying this nomogram in NAT efficacy prediction. Results: TILs were significantly correlated with body mass index (BMI), tumor differentiation, ER, PR, HER2 expression, Ki67, blood biochemical indicators including total bilirubin (TBIL), indirect bilirubin (IBIL), total protein (TP), Globulin (GLOB), inorganic phosphorus (IP), calcium (Ca). In which ER expression level [OR = 0.987, 95%CI (0.982-0.992), p < 0.001], IP [OR = 4.462, 95%CI (1.171∼17.289), p = 0.029], IBIL [OR = 0.906, 95%CI (0.845-0.966), p = 0.004] and TP [OR = 1.053, 95%CI (1.010-1.098, p = 0.016)] were independent predictors of TILs. Then nomogram was established, for which calibration curves (C-index = 0.759) and ROC curve (AUC = 0.759, 95%CI 0.717-0.801) in training sets, calibration curves (C-index = 0.708) and ROC curve (AUC = 0.708, 95%CI 0.617-0.800) in validation sets demonstrated great evaluation efficiency. Besides, independent NAT cohort verified this nomogram can distinguish patients with greater NAT efficacy (p = 0.041). Conclusion: The finds of clinicopathological factors associated with TILs could help clinicians to understand the tumor immunity of BRCA and improve treatment system for patients, and the established nomogram with high evaluation efficiency may be used as a complement tool for distinguishing patients with better NAT efficacy.

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Magnetic resonance imaging and molecular features associated with tumor-infiltrating lymphocytes in breast cancer.

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Magnetic resonance imaging and molecular features associated with tumor-infiltrating lymphocytes in breast cancer.

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