Prediction of Prognostic Factors and Genotypes in Patients With Breast Cancer Using Multiple Mathematical Models of MR Diffusion Imaging

Front Oncol. 2022 Jan 31;12:825264. doi: 10.3389/fonc.2022.825264. eCollection 2022.


Purpose: To explore the clinical value of apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI) based on diffusion-weighted MRI (DW-MRI) for predicting genotypes and prognostic factors of breast cancer.

Materials and methods: A total of 227 patients with breast cancer confirmed by pathology were reviewed retrospectively. Diffusion-weighted imaging (DWI), IVIM, and DKI were performed in all patients. The corresponding ADC, true diffusion coefficient (D), perfusion-related diffusion coefficient (D*), perfusion fraction (f), mean diffusion rate (MD), and mean kurtosis value (MK) were measured. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve were used to analyze the diagnostic efficacy in predicting the Nottingham prognostic index (NPI), the expression of antigen Ki-67, and the molecular subtypes of breast cancer. The nomogram of the combined genotype-prediction model was established based on the multivariate logistic regression model results.

Results: D* and MK values were significantly higher in the high-grade Nottingham group (NPI ≥ 3.4) than the low-grade Nottingham group (NPI < 3.4) (p < 0.01). When D* ≥ 30.95 × 10-3 mm2/s and MK ≥ 0.69, the NPI tended to be high grade (with areas under the curve (AUCs) of 0.712 and 0.647, respectively). The combination of D* and MK demonstrated the highest AUC of 0.734 in grading NPI with sensitivity and accuracy of 71.7% and 77.1%, respectively. Additionally, higher D*, f, and MK and lower ADC and D values were observed in the high Ki-67 than low Ki-67 expression groups (p < 0.05). The AUC of the combined model (D + D* + f + MK) was 0.755, being significantly higher than that of single parameters (Z = 2.770~3.244, p = 0.001~0.006) in distinguishing high from low Ki-67 expression. D* and f values in the Luminal A subtype were significantly lower than in other subtypes (p < 0.05). Luminal B showed decreased D value compared with other subtypes (p < 0.05). The HER-2-positive subtype demonstrated increased ADC values compared with the Luminal B subtype (p < 0.05). Luminal A/B showed significantly lower D, D*, MD, and MK than the non-Luminal subtypes (p < 0.05). The combined model (D + D* + MD + MK) showed an AUC of 0.830 in diagnosing the Luminal and non-Luminal subtypes, which is significantly higher than that of a single parameter (Z = 3.273~4.440, p < 0.01). f ≥ 54.30% [odds ratio (OR) = 1.038, p < 0.001] and MK ≥ 0.68 (OR = 24.745, p = 0.012) were found to be significant predictors of triple-negative subtypes. The combination of f and MK values demonstrated superior diagnostic performance with AUC, sensitivity, specificity, and accuracy of 0.756, 67.5%, 77.5%, and 82.4%, respectively. Moreover, as shown in the calibration curve, strong agreements were observed between nomogram prediction probability and actual findings in the prediction of genotypes (p = 0.22, 0.74).

Conclusion: DWI, IVIM, and DKI, as MR diffusion imaging techniques with different mathematical models showed potential to identify the prognosis and genotype of breast cancer. In addition, the combination of these three models can improve the diagnostic efficiency and thus may contribute to opting for an appropriate therapeutic approach in clinic treatment.

Keywords: breast neoplasms; diffusion kurtosis imaging; diffusion-weighted imaging; intravoxel incoherent motion; magnetic resonance imaging.