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.
Highlights
Breast cancer is a heterogeneous tumor exhibiting five molecular types, classified by gene profiling and the expression of hormonal receptors such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor (HER2) [1]
Association between angiogenesis and HER2 expression has been described [67, 68]. These findings indicated that positive ER expression was associated with the inhibition of angiogenesis, while positive PR and HER2 expression was associated with the enhancement of angiogenesis
The present study on a relatively large cohort of subjects demonstrated that a low apparent diffusion coefficient (ADC) value is indicative of malignancy
Summary
Breast cancer is a heterogeneous tumor exhibiting five molecular types, classified by gene profiling and the expression of hormonal receptors such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor (HER2) [1]. Mammography is the primary diagnostic screening tool, despite its limitation in sensitivity and specificity, especially in regard to the dense breast [4, 5] Breast magnetic resonance imaging (MRI) has become an important adjunct modality in the evaluation of suspicious mammographically occult breast lesions, detection of tumor recurrence, and screening of women with high-risk cancer and those with breast implants [7]. It is useful in pre-operative tumor staging and in the assessment of post-therapy residual disease in a clinical setting [7]. The DCEMRI has been shown to have high sensitivity (93–99%) but with variable specificity (37–85%) [9]
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