Molecular subtypes of breast cancer identified by dynamically enhanced MRI radiomics: the delayed phase cannot be ignored.

OBJECTIVES: To compare the diagnostic performance of intratumoral and peritumoral features from different contrast phases of breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) by building radiomics models for differentiating molecular subtypes of breast cancer. METHODS: This retrospective study included 377 patients with pathologically confirmed breast cancer. Patients were divided into training set (n = 202), validation set (n = 87) and test set (n = 88). The intratumoral volume of interest (VOI) and peritumoral VOI were delineated on primary breast cancers at three different DCE-MRI contrast phases: early, peak, and delayed. Radiomics features were extracted from each phase. After feature standardization, the training set was filtered by variance analysis, correlation analysis, and least absolute shrinkage and selection (LASSO). Using the extracted features, a logistic regression model based on each tumor subtype (Luminal A, Luminal B, HER2-enriched, triple-negative) was established. Ten models based on intratumoral or/plus peritumoral features from three different phases were developed for each differentiation. RESULTS: Radiomics features extracted from delayed phase DCE-MRI demonstrated dominant diagnostic performance over features from other phases. However, the differences were not statistically significant. In the full fusion model for differentiating different molecular subtypes, the most frequently screened features were those from the delayed phase. According to the Shapley additive explanation (SHAP) method, the most important features were also identified from the delayed phase. CONCLUSIONS: The intratumoral and peritumoral radiomics features from the delayed phase of DCE-MRI can provide additional information for preoperative molecular typing. The delayed phase of DCE-MRI cannot be ignored. CRITICAL RELEVANCE STATEMENT: Radiomics features extracted and radiomics models constructed from the delayed phase of DCE-MRI played a crucial role in molecular subtype classification, although no significant difference was observed in the test cohort. KEY POINTS: The molecular subtype of breast cancer provides a basis for setting treatment strategy and prognosis. The delayed-phase radiomics model outperformed that of early-/peak-phases, but no differently than other phases or combinations. Both intra- and peritumoral radiomics features offer valuable insights for molecular typing.

MRI-based tumor shrinkage patterns after early neoadjuvant therapy in breast cancer: correlation with molecular subtypes and pathological response after therapy.

BACKGROUND: MRI-based tumor shrinkage patterns (TSP) after neoadjuvant therapy (NAT) have been associated with pathological response. However, the understanding of TSP after early NAT remains limited. We aimed to analyze the relationship between TSP after early NAT and pathological response after therapy in different molecular subtypes. METHODS: We prospectively enrolled participants with invasive ductal breast cancers who received NAT and performed pretreatment DCE-MRI from September 2020 to August 2022. Early-stage MRIs were performed after the first (1st-MRI) and/or second (2nd-MRI) cycle of NAT. Tumor shrinkage patterns were categorized into four groups: concentric shrinkage, diffuse decrease (DD), decrease of intensity only (DIO), and stable disease (SD). Logistic regression analysis was performed to identify independent variables associated with pathologic complete response (pCR), and stratified analysis according to tumor hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) disease subtype. RESULTS: 344 participants (mean age: 50 years, 113/345 [33%] pCR) with 345 tumors (1 bilateral) had evaluable 1st-MRI or 2nd-MRI to comprise the primary analysis cohort, of which 244 participants with 245 tumors had evaluable 1st-MRI (82/245 [33%] pCR) and 206 participants with 207 tumors had evaluable 2nd-MRI (69/207 [33%] pCR) to comprise the 1st- and 2nd-timepoint subgroup analysis cohorts, respectively. In the primary analysis, multivariate analysis showed that early DD pattern (OR = 12.08; 95% CI 3.34-43.75; p < 0.001) predicted pCR independently of the change in tumor size (OR = 1.37; 95% CI 0.94-2.01; p = 0.106) in HR+/HER2- subtype, and the change in tumor size was a strong pCR predictor in HER2+ (OR = 1.61; 95% CI 1.22-2.13; p = 0.001) and triple-negative breast cancer (TNBC, OR = 1.61; 95% CI 1.22-2.11; p = 0.001). Compared with the change in tumor size, the SD pattern achieved a higher negative predictive value in HER2+ and TNBC. The statistical significance of complete 1st-timepoint subgroup analysis was consistent with the primary analysis. CONCLUSION: The diffuse decrease pattern in HR+/HER2- subtype and stable disease in HER2+ and TNBC after early NAT could serve as additional straightforward and comprehensible indicators of treatment response. TRIAL REGISTRATION: Trial registration at https://www.chictr.org.cn/ . REGISTRATION NUMBER: ChiCTR2000038578, registered September 24, 2020.

Potential Antihuman Epidermal Growth Factor Receptor 2 Target Therapy Beneficiaries: The Role of MRI-Based Radiomics in Distinguishing Human Epidermal Growth Factor Receptor 2-Low Status of Breast Cancer.

BACKGROUND: Multiparametric MRI radiomics could distinguish human epidermal growth factor receptor 2 (HER2)-positive from HER2-negative breast cancers. However, its value for further distinguishing HER2-low from HER2-negative breast cancers has not been investigated. PURPOSE: To investigate whether multiparametric MRI-based radiomics can distinguish HER2-positive from HER2-negative breast cancers (task 1) and HER2-low from HER2-negative breast cancers (task 2). STUDY TYPE: Retrospective. POPULATION: Task 1: 310 operable breast cancer patients from center 1 (97 HER2-positive and 213 HER2-negative); task 2: 213 HER2-negative patients (108 HER2-low and 105 HER2-zero); 59 patients from center 2 (16 HER2-positive, 27 HER2-low and 16 HER2-zero) for external validation. FIELD STRENGTH/SEQUENCE: A 3.0 T/T1-weighted contrast-enhanced imaging (T1CE), diffusion-weighted imaging (DWI)-derived apparent diffusion coefficient (ADC). ASSESSMENT: Patients in center 1 were assigned to a training and internal validation cohort at a 2:1 ratio. Intratumoral and peritumoral features were extracted from T1CE and ADC. After dimensionality reduction, the radiomics signatures (RS) of two tasks were developed using features from T1CE (RS-T1CE), ADC (RS-ADC) alone and T1CE + ADC combination (RS-Com). STATISTICAL TESTS: Mann-Whitney U tests, the least absolute shrinkage and selection operator, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). RESULTS: For task 1, RS-ADC yielded higher area under the ROC curve (AUC) in the training, internal, and external validation of 0.767/0.725/0.746 than RS-T1CE (AUC = 0.733/0.674/0.641). For task 2, RS-T1CE yielded higher AUC of 0.765/0.755/0.678 than RS-ADC (AUC = 0.706/0.608/0.630). For both of task 1 and task 2, RS-Com achieved the best performance with AUC of 0.793/0.778/0.760 and 0.820/0.776/0.711, respectively, and obtained higher clinical benefit in DCA compared with RS-T1CE and RS-ADC. The calibration curves of all RS demonstrated a good fitness. DATA CONCLUSION: Multiparametric MRI radiomics could noninvasively and robustly distinguish HER2-positive from HER2-negative breast cancers and further distinguish HER2-low from HER2-negative breast cancers. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Time Course Changes of Synthetic Relaxation Time During Neoadjuvant Chemotherapy in Breast Cancer: The Optimal Parameter for Treatment Response Evaluation.

BACKGROUND: Synthetic MRI (syMRI) has enabled quantification of multiple relaxation parameters (T1/T2 relaxation time [T1/T2], proton density [PD]), and their longitudinal change during neoadjuvant chemotherapy (NAC) promises to be valuable parameters for treatment response evaluation in breast cancer. PURPOSE: To investigate the time course changes of syMRI parameters during NAC and evaluate their value as predictors for pathological complete response (pCR) in breast cancer. STUDY TYPE: Retrospective, longitudinal. POPULATION: A total of 129 women (median age, 50 years; range, 28-69 years) with locally advanced breast cancer who underwent NAC; all performed multiple conventional breast MRI examinations with added syMRI during NAC. FIELD STRENGTH/SEQUENCE: A 3.0 T, T1-weighted dynamic contrast enhanced and syMRI acquired by a multiple-dynamic, multiple-echo sequence. ASSESSMENT: Breast MRI was set at four time-points: baseline, after one cycle, after three or four cycles of NAC and preoperation. SyMRI parameters and tumor diameters were measured and their changes from baseline were calculated. All parameters were compared between pCR and non-pCR. Interaction between syMRI parameters and clinicopathological features was analyzed. STATISTICAL TESTS: Mann-Whitney U tests, random effects model of repeated measurement, receiver operating characteristic (ROC) analysis, interaction analysis. RESULTS: Median synthetic T1/T2/PD and tumor diameter generally decreased throughout NAC. Absolute T1 at early-NAC, T1, and PD at mid-NAC were significantly lower in the pCR group. After early-NAC, the T1 change was significantly higher in the pCR (median ± IQR, 18.17 ± 11.33) than the non-pCR group (median ± IQR, 10.90 ± 10.03), with the highest area under the ROC curves (AUC) of 0.769 (95% CI, 0.684-0.838). Interaction analysis showed that histological grade III patients had higher odds ratio (OR) (OR = 1.206) compared to grade II patients (OR = 1.067). DATA CONCLUSION: Synthetic T1 changes after one cycle of NAC maybe useful for early evaluating NAC response in breast cancer during whole treatment cycles. However, its discriminative ability is significantly affected by histological grade. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Delta-Radiomics Based on Dynamic Contrast-Enhanced MRI Predicts Pathologic Complete Response in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

OBJECTIVE: To investigate the value of delta-radiomics after the first cycle of neoadjuvant chemotherapy (NAC) using dynamic contrast-enhanced (DCE) MRI for early prediction of pathological complete response (pCR) in patients with breast cancer. METHODS: From September 2018 to May 2021, a total of 140 consecutive patients (training, n = 98: validation, n = 42), newly diagnosed with breast cancer who received NAC before surgery, were prospectively enrolled. All patients underwent DCE-MRI at pre-NAC (pre-) and after the first cycle (1st-) of NAC. Radiomic features were extracted from the postcontrast early, peak, and delay phases. Delta-radiomics features were computed in each contrast phases. Least absolute shrinkage and selection operator (LASSO) and a logistic regression model were used to select features and build models. The model performance was assessed by receiver operating characteristic (ROC) analysis and compared by DeLong test. RESULTS: The delta-radiomics model based on the early phases of DCE-MRI showed a highest AUC (0.917/0.842 for training/validation cohort) compared with that using the peak and delay phases images. The delta-radiomics model outperformed the pre-radiomics model (AUC = 0.759/0.617, p = 0.011/0.047 for training/validation cohort) in early phase. Based on the optimal model, longitudinal fusion radiomic models achieved an AUC of 0.871/0.869 in training/validation cohort. Clinical-radiomics model generated good calibration and discrimination capacity with AUC 0.934 (95%CI: 0.882, 0.986)/0.864 (95%CI: 0.746, 0.982) for training and validation cohort. Delta-radiomics based on early contrast phases of DCE-MRI combined clinicopathology information could predict pCR after one cycle of NAC in patients with breast cancer.

Contrast-free MRI quantitative parameters for early prediction of pathological response to neoadjuvant chemotherapy in breast cancer.

OBJECTIVES: To assess early changes in synthetic relaxometry after neoadjuvant chemotherapy (NAC) for breast cancer and establish a model with contrast-free quantitative parameters for early prediction of pathological response. METHODS: From March 2019 to January 2021, breast MRI were performed for a primary cohort of women with breast cancer before (n = 102) and after the first (n = 93) and second (n = 90) cycle of NAC. Tumor size, synthetic relaxometry (T1/T2 relaxation time [T1/T2], proton density), and ADC were obtained, and the changes after treatment were calculated. Prediction models were established by multivariate logistic regression; evaluated with discrimination, calibration, and clinical application; and compared with Delong tests, net reclassification (NRI), and integrated discrimination index (IDI). External validation was performed from February to June 2021 with an independent cohort of 35 patients. RESULTS: In the primary cohort, all parameters changed after early treatment. Synthetic relaxometry decreased to a greater degree in major histologic responders (MHR, Miller-Payne G4-5) compared with non-MHR (Miller-Payne G1-3). A model combining ADC after treatment, changes in T1 and tumor size, and cancer subtype achieved the highest AUC after the first (primary/validation cohort, 0.83/0.82) and second cycles (primary/validation cohort, 0.85/0.84). No difference of AUC (p ≥ 0.27), NRI (p ≥ 0.31), and IDI (p ≥ 0.32) was found between models with different cycles and size-measured sequences. Model calibration and decision curves demonstrated a good fitness and clinical benefit, respectively. CONCLUSIONS: Early reduction in synthetic relaxometry indicated pathological response to NAC. Contrast-free T1 and ADC combined with size and cancer subtype predicted effectively pathological response after one NAC cycle. KEY POINTS: • Synthetic MRI relaxometry changed after early neoadjuvant chemotherapy, which demonstrated pathological response for mass-like breast cancers. • Contrast-free quantitative parameters including T1 relaxation time and apparent diffusion coefficient, combined with tumor size and cancer subtype, stratified major histologic responders. • A contrast-free model predicted an early pathological response after the first treatment cycle of neoadjuvant chemotherapy.

Associations of MTHFR and MTRR polymorphisms with serum lipid levels in Chinese hypertensive patients.

OBJECTIVE: To examine the effects of the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene polymorphisms and their interactions with environmental factors on serum lipid levels. METHODS: We investigated totally 340 patients with essential hypertension, from Dongzhi community, Anhui, China. High-throughput TaqMan allelic discrimination assay was used for the genotyping of MTHFR C677T (Ala222Val), MTHFR A1298C (Glu429Ala), MTRR A66G (Ile22Met), and MTRR His595Tyr. RESULTS: Compared with the MTRR 66AA genotype carriers, the GG genotype carriers had lower serum total cholesterol (TC) levels (adjusted ß ± standard error [SE]: -0.5 ± 0.2 mmol/L; P = .003) and low-density lipoprotein cholesterol (LDL-C) levels (adjusted ß ± SE: -0.4 ± 0.2 mmol/L; P = .005). Their false discovery rate (FDR)-adjusted P values were 0.056 and 0.056, respectively. We further found that there was a statistically significant interaction between 677TT genotype and sex in their associations with LDL levels (P interaction = .020), and significant interaction between 677TT genotype and smoking on LDL levels (P interaction = .036). A similar pattern of interaction was found between 66GG and drinking on levels of TC (P interaction = .034) and LDL (P interaction = .020). However, there were no significant interactions observed after FDR adjustment. CONCLUSION: Both MTHFR and MTRR gene polymorphisms could be important genetic determinants of serum lipid levels in Chinese patients with hypertension. These findings need to be replicated in a larger sample.