The potential of total choline (tCho) signal-to-noise ratio (SNR) (ChoSNR) and tumor volume in the assessment of tumor response in locally advanced breast cancer (LABC) patients (n = 30) undergoing neoadjuvant chemotherapy (NACT) was investigated using magnetic resonance spectroscopic imaging (MRSI) and conventional MRI at 1.5 T. Experiments were carried out sequentially at four time-points: prior to therapy and after I, II and III NACT and ChoSNR, and the tumor volume was measured. The MR response was compared with the clinical response. Sequential data of 25 patients were retrospectively analyzed by classifying them as clinical responders and non-responders. In 14 responders, the pre-therapy ChoSNR was 7.8 +/- 5.1. In 10/14 responders, no choline was observed after III NACT while in the remaining four patients the ChoSNR was reduced to 3.6 +/- 1.1 (p < 0.05). Non-responders showed no statistically significant change in ChoSNR. After III NACT, the tumor volume reduced by 84.0 +/- 14.8% in responders. Using receiver operating curve (ROC) analysis, cut-off values of 53% for ChoSNR and 47.5% for volume were obtained to differentiate responders from non-responders. The sensitivity to detect responders from non-responders using ChoSNR was 85.7% with 91% specificity while 100% sensitivity was observed for volume but with reduced specificity of 73%. Our results indicate that ChoSNR may serve as a useful parameter to predict tumor response to NACT with higher specificity compared to volume, suggesting its potential in effective treatment management.

The association of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status of breast cancer patients with total choline (tCho) concentration and tumor volume was investigated using in vivo proton magnetic resonance spectroscopy and MRI at 1.5 T. Values for tCho concentration were determined in 120 locally advanced breast cancer patients (stages IIB, IIIA, IIIB, and IIIC), 31 early breast cancer patients (stage IIA), 38 patients with benign lesions, and 37 controls. Significantly higher tCho concentration and lower tumor volume were observed in early breast cancer patients compared to locally advanced breast cancer patients (P<0.05). tCho concentration and tumor volume did not correlate with age and menstruation. tCho cutoff values were obtained for the differentiation of malignant from benign breast tissues (2.54 mmol/kg); malignant versus normal (1.45 mmol/kg) and benign versus normal tissues (0.82 mmol/kg). Estrogen receptor negative patients showed significantly larger tumor volumes, indicating higher angiogenesis with aggressive tumor behavior. Nontriple negative and triple positive patients had a significantly higher tCho concentration compared to triple negative patients (P<0.05), indicating complex molecular mechanism of cell proliferation and the molecular heterogeneity of breast lesions. The results indicate the potential use of integration of breast 1H magnetic resonance spectroscopy in diagnostic workup.

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.

Observation of lactose peak with higher ADC in the breast tissue of healthy lactating women volunteers may aid in differentiation of changes that occur in breast tissue due to normal physiological conditions like lactation compared with malignant transformation.

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