Potential of Diffusion-Weighted Imaging in the Characterization of Malignant, Benign, and Healthy Breast Tissues and Molecular Subtypes of Breast Cancer

Abstract

The role of apparent diffusion coefficient (ADC) in the diagnosis of breast cancer and its association with molecular biomarkers was investigated in 259 patients with breast cancer, 67 with benign pathology, and 54 healthy volunteers using diffusion-weighted imaging (DWI) at 1.5 T. In 59 breast cancer patients, dynamic contrast-enhanced MRI (DCEMRI) was also acquired. Mean ADC of malignant lesions was significantly lower (1.02 ± 0.17 × 10−3 mm2/s) compared to benign (1.57 ± 0.26 × 10−3 mm2/s) and healthy (1.78 ± 0.13 × 10−3 mm2/s) breast tissues. A cutoff ADC value of 1.23 × 10−3 mm2/s (sensitivity 92.5%; specificity 91.1%; area under the curve 0.96) to differentiate malignant from benign diseases was arrived by receiver operating curve analysis. In 10/59 breast cancer patients, indeterminate DCE curve was seen, while their ADC value was indicative of malignancy, implying the potential of the addition of DWI in increasing the specificity of DCEMRI data. Further, the association of ADC with tumor volume, stage, hormonal receptors [estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor (HER2)], and menopausal status was investigated. A significant difference was seen in tumor volume between breast cancer patients of stages IIA and IIIA, IIB and IIIA, and IIB and III (B + C), respectively (P < 0.05). Patients with early breast cancer (n = 52) had significantly lower ADC and tumor volume than those with locally advanced breast cancer (n = 207). No association was found in ADC and tumor volume with the menopausal status. Breast cancers with ER−, PR−, and triple-negative (TN) status showed a significantly larger tumor volume compared to ER+, PR+, and non-triple-negative (nTN) cancers, respectively. Also, TN tumors showed a significantly higher ADC compared to ER+, PR+, and nTN cancers. Patients with ER− and TN cancers were younger than those with ER+ and nTN cancers. The present study demonstrated that ADC may increase the diagnostic specificity of DCEMRI and be useful for treatment management in clinical setting. Additionally, it provides an insight into characterization of molecular types of breast cancer and may serve as an indicator of metabolic reprograming underlying tumor proliferation.

Rim sign and histogram analysis of apparent diffusion coefficient values on diffusion-weighted MRI in triple-negative breast cancer: Comparison with ER-positive subtype

“…[24,25] However, prior studies [8,22] have found that TNBC has a higher mean ADC value than other breast cancer subtypes due to TNBC's necrotic components. Our results confirmed findings of higher mean ADC value (P<0.001) in TNBC in a univariate analysis.…”

Diffusion‐weighted imaging features of breast tumours and the surrounding stroma reflect intrinsic heterogeneous characteristics of molecular subtypes in breast cancer

“…Moreover, ADC has been utilized as an indicator of tumour aggressiveness, Ki‐67 expression, tumour cellularity and the expression of prognosis biomarkers in breast cancer . Recent studies have reported a correlation between ADC and the molecular markers of breast cancer . In addition to direct analysis of the entire tumour, DWI information on the breast tumour–stromal boundary and adjacent tissue surrounding the tumour has also been combined to associate DWI parameters with pathological factors or to predict responses to treatment …”

“…[19][20][21][22][23] Recent studies have reported a correlation between ADC and the molecular markers of breast cancer. [24][25][26][27] In addition to direct analysis of the entire tumour, DWI information on the breast tumour-stromal boundary and adjacent tissue surrounding the tumour has also been combined to associate DWI parameters with pathological factors or to predict responses to treatment. 28,29 In this study, we hypothesized that the ADC values of the tumour and surrounding peritumoral stroma may be distinct and may reflect the heterogeneity of the tumour microenvironment in breast cancer.…”

Application of in vivo MR methods in the study of breast cancer metabolism

“…Moreover, during the progression of disease as in LABC, necrosis is commonly seen, and Sharma et al have reported that ADC is a reliable indicator to monitor these islets of necrotic regions (Figure ). Patients with early breast cancer had significantly lower ADC compared with those with LABC, and no association was found between ADC and menopausal status . These results thus provide information on tumor biology and microstructural features.…”