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The role of diffusion-weighted magnetic resonance imaging (DWI) to differentiate breast lesions in vivo was evaluated. Sixty women (mean age, 53 years) with 81 breast lesions were enrolled. A coronal echo planar imaging (EPI) sequence sensitised to diffusion (b value=1,000 s/mm(2)) was added to standard MR. The mean diffusivity (MD) was calculated. Differences in MD among cysts, benign lesions and malignant lesions were evaluated, and the sensitivity and specificity of DWI to diagnose malignant and benign lesions were calculated. The diagnosis was 18 cysts, 21 benign and 42 malignant nodules. MD values (mean +/- SD x 10(-3) mm(2)/s) were (1.48 +/- 0.37) for benign lesions, (0.95 +/- 0.18) for malignant lesions and (2.25 +/- 0.26) for cysts. Different MD values characterized different malignant breast lesion types. A MD threshold value of 1.1 x 10(-3) mm(2)/s discriminated malignant breast lesions from benign lesions with a specificity of 81% and sensitivity of 80%. Choosing a cut-off of 1.31 x 10(-3) mm(2)/s (MD of malignant lesions -2 SD), the specificity would be 67% with a sensitivity of 100%. Thus, MD values, related to tumor cellularity, provide reliable information to differentiate malignant breast lesions from benign ones. Quantitative DWI is not time-consuming and can be easily inserted into standard clinical breast MR imaging protocols.

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Background and objectives: Cancer stem cells (CSCs) have been implicated in tumor initiation, recurrence, metastatic spread and poor survival in multiple tumor types, breast cancers included. CSCs selectively overexpress key mitochondrial-related proteins and inhibition of mitochondrial function may represent a new potential approach for the eradication of CSCs. Because mitochondria evolved from bacteria, many classes of FDA-approved antibiotics, including doxycycline, actually target mitochondria. Our clinical pilot study aimed to determine whether short-term pre-operative treatment with oral doxycycline results in reduction of CSCs in early breast cancer patients.Methods: Doxycycline was administered orally for 14 days before surgery for a daily dose of 200 mg. Immuno-histochemical analysis of formalin-fixed paraffin-embedded (FFPE) samples from 15 patients, of which 9 were treated with doxycycline and 6 were controls (no treatment), was performed with known biomarkers of “stemness” (CD44, ALDH1), mitochondria (TOMM20), cell proliferation (Ki67, p27), apoptosis (cleaved caspase-3), and neo-angiogenesis (CD31). For each patient, the analysis was performed both on pre-operative specimens (core-biopsies) and surgical specimens. Changes from baseline to post-treatment were assessed with MedCalc 12 (unpaired t-test) and ANOVA.Results: Post-doxycycline tumor samples demonstrated a statistically significant decrease in the stemness marker CD44 (p-value < 0.005), when compared to pre-doxycycline tumor samples. More specifically, CD44 levels were reduced between 17.65 and 66.67%, in 8 out of 9 patients treated with doxycycline. In contrast, only one patient showed a rise in CD44, by 15%. Overall, this represents a positive response rate of nearly 90%. Similar results were also obtained with ALDH1, another marker of stemness. In contrast, markers of mitochondria, proliferation, apoptosis, and neo-angiogenesis, were all similar between the two groups.Conclusions: Quantitative decreases in CD44 and ALDH1 expression are consistent with pre-clinical experiments and suggest that doxycycline can selectively eradicate CSCs in breast cancer patients in vivo. Future studies (with larger numbers of patients) will be conducted to validate these promising pilot studies.

Mammography and stereotactic biopsy still remain the only techniques for characterising microcalcifications. MRI cannot be considered a diagnostic tool for evaluating microcalcifications. It is, however, useful for identifying DCIS with more aggressive histological grades. An important application of MRI in patients with DCIS associated with suspicious microcalcifications could be to evaluate disease extension after a microhistological diagnosis of malignancy, as it allows a more accurate presurgical planning.