Assessment of grating-based X-ray phase-contrast CT for differentiation of invasive ductal carcinoma and ductal carcinoma in situ in an experimental ex vivo set-up.

OBJECTIVE: Limited contrast between healthy and tumour tissue is a limiting factor in mammography and CT of the breast. Phase-contrast computed tomography (PC-CT) provides improved soft-tissue contrast compared with absorption-based techniques. In this study, we assessed the technical feasibility of grating-based PC-CT imaging of the breast for characterisation of ductal carcinoma in situ (DCIS). METHODS: Grating-based PC-CT was performed on one breast specimen containing an invasive ductal carcinoma and DCIS using monochromatic radiation of 23 keV. Phase-contrast and absorption-based images were compared qualitatively and quantitatively with histopathology in a blinded fashion. RESULTS: Grating-based PC-CT showed improved differentiation of soft-tissue components. Circular structures of high phase-shift contrast corresponding to the walls of the dilated ductuli of the DCIS were visualised with a contrast-to-noise ratio (CNR) of 9.6 using PC-CT but were not detectable on absorption-based images (CNR = 0.27). The high phase-shift structures of the dilated ductuli were identifiable in the PC-CT volume data set allowing for 3D characterisation of DCIS. CONCLUSIONS: Our results indicate that unlike conventional CT, grating-based PC-CT may allow the differentiation between invasive carcinoma and intraductal carcinoma and healthy breast tissue and provide 3D visualisation of DCIS.

High-resolution, low-dose phase contrast X-ray tomography for 3D diagnosis of human breast cancers.

Mammography is the primary imaging tool for screening and diagnosis of human breast cancers, but ~10-20% of palpable tumors are not detectable on mammograms and only about 40% of biopsied lesions are malignant. Here we report a high-resolution, low-dose phase contrast X-ray tomographic method for 3D diagnosis of human breast cancers. By combining phase contrast X-ray imaging with an image reconstruction method known as equally sloped tomography, we imaged a human breast in three dimensions and identified a malignant cancer with a pixel size of 92 µm and a radiation dose less than that of dual-view mammography. According to a blind evaluation by five independent radiologists, our method can reduce the radiation dose and acquisition time by ~74% relative to conventional phase contrast X-ray tomography, while maintaining high image resolution and image contrast. These results demonstrate that high-resolution 3D diagnostic imaging of human breast cancers can, in principle, be performed at clinical compatible doses.

CEA-, Her2/neu-, BCRP- and Hsp27-positive microparticles in breast cancer patients.

BACKGROUND: This is the first prospective case-control study that evaluates the expression of tumour-specific antigens on circulating microparticles (MP) in breast cancer patients and in women with benign breast tumour. MATERIALS AND METHODS: MP were determined by flow cytometry in patients with breast cancer (n=34; T1 (n=19) and T2 (n=15)) and women with benign breast tumour (n=19). RESULTS: Patients with lymph node metastases (N1, n=9) showed significantly higher numbers of annexin V(+) MP (p=0.042), CD66(+) MP (p=0.045), BCRP1(+) MP (breast cancer resistance protein) (p=0.025) and Hsp27(+) MP (p=0.034) than controls. Furthermore, T1 patients had significantly higher levels of annexin V(+) MP (p=0.004), CD66(+) MP (p=0.025), BCRP1(+) MP (p=0.008) and Hsp27(+) MP (p=0.02) than controls. CONCLUSION: Significant differences are present between breast cancer patients with lymph node metastases and controls concerning annexin V-, CD66-, BCRP1- and Hsp27-positive MP. To specify the role of these MP subpopulations in breast cancer progression, further studies enrolling larger patient groups are part of ongoing research.

Thyroid function in breast cancer patients.

BACKGROUND: Recent studies indicate a possible relationship between hypothyroidism and breast cancer in vivo. In addition, oestrogen-like effects of thyroid hormones on breast cancer cell growth are seen in vitro. Therefore, this study evaluated thyroid function in breast cancer patients, women with benign breast tumour and healthy controls. PATIENTS AND METHODS: Breast cancer patients (n=65), women with carcinoma in situ (n=13) or benign breast tumour (n=27), and healthy controls (n=38) were included in the study. Thyroid history was reported. Thyroid hormones (fT4, fT3, TSH) and thyroid antibodies (TPO, TRAK and TG) were determined. Statistical analysis was performed by Mann-Whitney U and Fisher's exact test (p<0.005 significant). RESULTS: fT3 and fT4 levels were highest in breast cancer patients, and differed significantly from controls (fT3 and fT4: p<0.001) as well as from patients with benign breast tumour (fT3: p=0.021; fT4: p=0.017). TSH was highest in the control group without reaching significance. With regard to TRAK antibodies, breast cancer patients showed the highest levels differing significantly from women with benign breast tumours (p=0.048). CONCLUSION: Significant differences in fT3/fT4 as well as TRAK levels were observed among breast cancer patients, women with benign breast tumours and healthy controls. Further studies using larger patient groups are part of ongoing research.

Platelet-derived microparticles and coagulation activation in breast cancer patients.

In the mid 1800s Trousseau observed cancer-associated thrombosis, of which the underlying pathogenesis still remains unknown. We performed a prospective study on platelet-derived microparticles (PMP) and their procoagulant potential in breast cancer patients. Fifty-eight breast cancer patients and 13 women with benign breast tumors were included in the study. Microparticles (MP) were examined by electron microscopy and FACS analysis using labels for annexin V (total numbers), CD61 (PMP), CD62P and CD63 (activated platelets), CD62E (endothelial cells), CD45 (leukocytes) as well as CD142 (tissue factor). Prothrombin fragment 1+2 (F1+2) and thrombin generation were measured as blood coagulation markers. Numbers of annexin V+-MP were highest in breast cancer patients with larger tumor size (T2; median = 5,637 x 10(6)/l; range = 2,852-8,613) and patients with distant metastases (M1; median = 6,102 x 10(6)/l; range = 3,350-7,445), and differed significantly from patients with in-situ tumor (Tis; median = 3,220 x 10(6)/l; range = 2,277-4,124; p = 0.019), small tumor size (T1; median = 3,281 x 10(6)/l; range = 2,356-4,861; p = 0.043) and women with benign breast tumor (median = 4,108 x 10(6)/l; range = 2,530-4,874; p = 0.040). A total of 82.3% of MP were from platelets, 14.6 % from endothelial cells and 0.3% from leukocytes. Less than 10% of PMP showed degranulation markers. Larger tumor size (T2) and metastases correlated with high counts of PMP and with highest F1+2 levels. Since prothrombin levels and thrombin generation did not parallel MP levels, we speculate that MP act in the microenvironment of tumor tissue and may thus not be an exclusive parameter reflecting in-vivo procoagulant activity.

Circulating microparticles in breast cancer patients: a comparative analysis with established biomarkers.

BACKGROUND: The aim of the present prospective case-control study was to evaluate the putative relevance of circulating microparticles (MP) as a biomarker in breast cancer patients. MATERIALS AND METHODS: Endothelial cell-(EMP) and leukocyte-derived MP (LMP) were determined by flow cytometry in breast cancer patients (n = 41) and healthy controls (n = 25) and compared to carcinoembryonic antigen (CEA), cancer antigen (CA)15-3 and von Willebrand factor antigen (vWF) levels by specificity-sensitivity profiles. RESULTS: LMP, CEA and CA15-3 levels differed significantly between breast cancer patients and controls, whereas EMP and vWF did not. The specificity-sensitivity profiles of LMP and CA15-3 were similar. CONCLUSION: Increasing levels of circulating LMP (CD45+), CEA and CA15-3 correlated with increasing tumor size, thus reflecting disease stage. LMP showed an equal specificity-sensitivity profile to the established marker CA15-3 and therefore might have the potential to become a new biomarker in breast cancer patients.