Validity of computed mean compressed fibroglandular tissue thickness and breast composition for stratification of masking risk in Japanese women.

BACKGROUND: The volumetric measurement system for mammographic breast density is a high-precision objective method for evaluating the percentage of fibroglandular tissue volume (FG%). Nonetheless, FG% does not precisely correlate with subjective visual estimation (SVE) and shows poor evaluation performance regarding masking risk in patients with comparatively thin compressed breast thickness (CBT), commonly found in Japanese women. We considered that the mean compressed fibroglandular tissue thickness (mCGT), which incorporates the CBT element into the evaluation of breast density, may better predict masking risk. METHODS: Volumetric measurements and SVEs were performed on mammograms of 108 breast cancer patients from our center. mCGT was calculated as the product of CBT and FG%. SVE was classified using the Breast Imaging-Reporting and Data System classification, 5th edition. Subsequently, the performance of mCGT, SVE, and FG% in predicting masking risk was estimated using the AUC. RESULTS: The AUC values of mCGT and SVE were 0.84 (95% confidence interval, 0.71-0.92) and 0.78 (0.66-0.86), respectively (P = 0.16). The AUC of the FG% was 0.65 (0.52-0.77), which was significantly lower than that of mCGT (P < 0.001). The sensitivity and specificity of mCGT in predicting negative detection were 89% and 71%, respectively; of SVE 83% and 61% (versus 72% and 57% with FG%), suggesting that mCGT was superior to FG% in both sensitivity and specificity, and comparable with SVE. CONCLUSIONS: Objective mCGT calculated from the volumetric measurement system will highly likely be useful in evaluating breast density and supporting visual assessment for masking risk stratification.

Can quantitative evaluation of mammographic breast density, "volumetric measurement", predict the masking risk with dense breast tissue? Investigation by comparison with subjective visual estimation by Japanese radiologists.

BACKGROUND: Sensitivity to detect breast cancer (BC) is not high in a dense breast due to masking in mammography. To evaluate the breast density, a volumetric measurement system has been recently developed that measures the percent fibroglandular tissue volume (percent FGV, hereafter termed as "FG%") to the breast volume (BV). This study was designed to investigate whether evaluation using FG% can accurately predict the masking risk by comparing with the current standard method of subjective visual estimation (SVE). METHODS: Using pre-biopsy mammograms of 114 cases histopathologically diagnosed with BC in our facility, SVE based on BI-RADS (5th edition) and volumetric measurements of FG% were conducted. Performance to predict the masking risk was evaluated using the area under the receiver operating characteristic curve (AUC). Relationship between these parameters and the masking risk was evaluated by the adjusted multivariate linear regression analysis. RESULTS: The AUC of SVE values was 0.742 (95% CI 0.641-0.822), while that of FG% was as significantly low as 0.560 (95% CI 0.427-0.685) (P = 0.0014). The SVE values correlated with the detection of BC in mammography (P = 0.0035), but there was no significant relationship with FG% (P = 0.74). The median BV and FGV were 313 cm3 (IQR 191-440) and 63 cm3 (IQR 44-102), respectively. The FGV was comparable to the data for Caucasian women reported in previous studies, but the BV was one-half of the previous data. CONCLUSION: The current volumetric measurement system to evaluate FG% to BV was found to be insufficient in the performance to predict the masking risk in Japanese women with relatively small-sized breasts.

Diagnostic performance of digital breast tomosynthesis and full-field digital mammography with new reconstruction and new processing for dose reduction.

BACKGROUND: The main barrier to adoption of digital breast tomosynthesis (DBT) plus full-field digital mammography (FFDM) is radiation exposure dose. The purpose of this study was to evaluate the diagnostic performance of DBT plus FFDM, both with newly developed technology (nd), at a dose comparable to that of the conventional FFDM alone. METHODS: Nine hundred and thirteen participants were recruited from May 2014 to January 2016 consecutively. For each subject, the exposure setting for DBT(nd) + FFDM(nd) was also used for the conventional FFDM alone. Retrospective reader studies were performed: DBT(nd) + FFDM(nd) (142 cases, including 42 cancer cases) and conventional FFDM (258 cases, including 87 cancer cases). Eight radiologists provided Japanese categorizations and probability of malignancy independently. Diagnostic performance was assessed by comparing sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Two-sided P values were calculated. RESULTS: DBT(nd) + FFDM(nd) showed sensitivity and AUC significantly increased over the conventional FFDM (85.4 vs. 80.3%, P = 0.015 and 90.9 vs. 88.3%, P = 0.049) and specificity did not significantly increase (89.6 vs. 88.4%, P = 0.52). The mean glandular dose (MGD) difference of DBT(nd) + FFDM(nd) and conventional FFDM was not significant (difference - 0.11 mGy, P = 0.08). CONCLUSIONS: In this study population, DBT plus FFDM, both with newly developed technology, provided diagnostic performance improved over the conventional FFDM alone, even at comparable MGD.

Detectability comparison of modes in dual-mode digital breast tomosynthesis.

BACKGROUND: The objectives of this study were: (1) to evaluate the detectability of full-field digital mammography (FFDM) plus dual-mode digital breast tomosynthesis (DBT) and compare it with that of FFDM alone and (2) to compare the detectability of high-resolution-mode (HR mode used with 40°-angle imaging, 100-µm pixel size, and higher dose) DBT with that of standard-mode (ST mode used with 15°-angle imaging, 150-µm pixel size, and lower dose) DBT for diagnostic evaluation. MATERIALS: The local Institutional Review Board approved this retrospective study of two different sets of cases. All participants gave written informed consent. FFDM and DBT images of 471 women who were recalled were acquired between August 2013 and October 2014. HR mode and ST mode were applied to 155 breasts and 157 breasts, respectively. The cases of both modes were selected randomly. Eight radiologists interpreted the images. The detectability for recall cases and for follow cases, and area under the receiver operating characteristic curve (AUC) were calculated. RESULTS: Adding DBT to FFDM significantly increased the detectability for recall cases and AUC relative to those of FFDM alone (HR mode 8.9 %; 95 % confidence interval (CI) 5.7, 15.0 %; P = 0.013 and 4.9 %; 95 % CI 2.1, 7.7 %; P = 0.001; ST mode 8.3 %; 95 % CI 4.1, 12.1 %; P = 0.007 and 2.9 %; 95 % CI 0.5, 5.3 %; P = 0.02), whereas the detectability for follow cases did not significantly differ. The AUC increase was significantly higher in HR mode than in ST mode (1.5 %; 95 % CI 0.5, 3.7 %; P = 0.023). CONCLUSION: Adding HR-mode or ST-mode DBT to FFDM significantly improved the detectability for diagnostic evaluation case.

Circulating tumor cells detected by reverse transcription-polymerase chain reaction for carcinoembryonic antigen mRNA: distinguishing follicular thyroid carcinoma from adenoma.

BACKGROUND: We prospectively tested whether circulating tumor cells could be detected in peripheral blood of patients with thyroid tumors by a reverse transcription-polymerase chain reaction (RT-PCR) to detect carcinoembryonic antigen (CEA) messenger RNA (mRNA). METHODS: We assayed for CEA mRNA by RT-PCR in peripheral blood sampled before and 2 to 3 weeks after curative surgery for thyroid tumors in 121 patients. Blood samples from 7 patients with chronic thyroiditis and 7 healthy subjects served as controls. RESULTS: No control samples were positive for CEA mRNA by RT-PCR. Of 121 preoperative samples from patients with thyroid tumor, 6 were positive (5.0%). Preoperative frequencies of CEA mRNA positivity in benign tumor, papillary carcinoma, follicular variant papillary carcinoma, minimally invasive follicular carcinoma, and widely invasive follicular carcinoma were 0%, 0%, 0%, 44.4% (4/9), and 50.0% (2/4), respectively. Among positive patients only one, who had widely invasive follicular carcinoma, remained positive after surgery. CONCLUSIONS: RT-PCR detection of tumor cells in preoperative blood often can distinguish malignant from benign follicular thyroid tumors.

The alpha4 residues of human DNA topoisomerase IIalpha function in enzymatic activity and anticancer drug sensitivity.

We introduced a series of Pro substitutions within and near the alpha4 helix, a part of the breakage/rejoining region, in human DNA topoisomerase IIalpha, and analyzed if this region is involved in determination of anti-cancer drug sensitivity in a temperature- sensitive yeast strain (top2-4 allele). Among the 19 mutants generated, H759P and N770P showed resistance to etoposide and doxorubicin at the non-permissive temperature, where cell growth depends on activity of the human enzyme. For these residues, mutants with an Ala substitution were further created, in which H759A also showed resistance to etoposide. H759P, H759A and N770P were expressed, purified and subjected to in vitro measurement of drug sensitivity. They generated lower amounts of the etoposide-induced cleavable complexes, and were also found to have lower decatenation activity than the wild-type. In the crystal structure, the yeast equivalent of His759 is found in the vicinity of the Arg713, a putative anchoring residue of the 3'-side of cleaved DNA strands. These results suggest that His759 and the other alpha4 helix residues are involved in the enzymatic activity and drug sensitivity of human DNA topoisomerase IIalpha, via interaction with cleaved DNA.

Function of the loop residue Thr792 in human DNA topoisomerase II alpha.

We studied the mutation effect of one of the putative loop residues Thr792 in human DNA topoisomerase II alpha (TOP2 alpha). Thr792 mutants were expressed from high or low copy plasmids in a temperature sensitive yeast strain deficient in TOP2 (top2-1). When expressed from a high copy plasmid, mutants with small side chains complemented the yeast defect; however, from a low copy plasmid, only wild-type, Ser, and Cys substitution mutants complemented the yeast defect. Interestingly, at the permissive temperature other mutants (e.g., Val, Gly, and Glu substitutions) showed the dominant negative effect to the top2-1 allele, which was not observed by the control alpha 4-helix mutants. T792E mutant was 10-fold less active than wild-type and the T792P had no decatenation activity in vitro. These results suggest that Thr792 in human TOP2 alpha is involved in enzyme catalysis.