MRI detection of distinct incidental cancer in women with primary breast cancer studied

Background: Prior single institution studies suggest MRI may improve the assessment of the extent of cancer within the breast, and thus reduce the risk of leaving macroscopic disease in the breast following breast conservation therapy. We report on the rate of MRI and mammography detection of foci of distinct incidental cancer in a prospective, multi center trial involving 426 women with confirmed breast cancer at 15 institutions in the US, Canada, and Germany. Methods: Women underwent mammography and MRI prior to biopsy of the suspicious index lesion. Additional incidental lesions (IL) greater than 2 cm from the index lesion that were detected by mammography and MRI were noted and characterized. Biopsy recommendations were associated with ILs given an assessment of suspicious or highly suspicous (BiRads 4 and 5). These assessments were considered a positive test. Results: MRI had a significantly higher yield of confirmed cancer ILs than mammography (0.18 (95%CI: 0.142-0.214) for MRI versus 0.072 (95%CI: 0.050-0.100) for mammography). The cancer ILs detected by MRI alone appeared to be similar to those detected by mammography with respect to size and histology. The percentage of biopsies of ILs that resulted in a cancer diagnosis was similar between Philadelphia, PA 19104, Fax: 215-662-7238, 215-662-301

Self-Referral for Screening Mammography

Patients can obtain screening mammograms without a physician's referral, leading to potential problems in clinical care. Because of the complexity of self-referral and the limitations of prior studies, we examined this phenomenon in a representative sample of mammography facilities. A questionnaire was given to all women obtaining mammograms at nine Connecticut mammography facilities during a 2-week period. Facilities included mobile sites, urban fixed sites, and rural fixed sites. Responses were categorized according to whether or not the woman had seen a primary care provider within the last year and whether or not she had received a recommendation to obtain a mammogram. The response rate was 62% (732 of 1,189), and the mean age of respondents was 58 years (range, 30–100 years). Self-referred women, defined as those without a recent visit to a primary care clinician and without a clinician's recommendation for a mammogram, constituted 6% of respondents. Self-referred women were significantly more likely to use mobile facilities (78% vs 33%, p < .01) and be under 50 years of age (44% vs 28%, p = .02) compared with provider-referred women who had recently seen their provider. We conclude that younger women are obtaining screening mammograms without clear evidence of having seen their primary care provider in the previous year or having received a referral from their provider. Self-referral is especially common at mobile mammography facilities. Further study is needed to assess the clinical impact of self-referral on mass screening programs

Diagnostic architectural and dynamic features at breast MR imaging: multicenter study. Radiology 238

Purpose: To prospectively determine the prevalence and predictive value of three-dimensional (3D) and dynamic breast magnetic resonance (MR) imaging and contrast material kinetic features alone and as part of predictive diagnostic models. Materials and Methods: The study protocol was approved by the institutional review board or ethics committees of all participating institutions, and informed consent was obtained from all participants. Although study data collection was performed before HIPAA went into effect, standards that would be compliant with HIPAA were adhered to. Data from the International Breast MR Consortium trial 6883 were used in the analysis. Women underwent 3D (minimum spatial resolution, 0.7 ϫ 1.4 ϫ 3 mm; minimal temporal resolution, 4 minutes) and dynamic two-dimensional (temporal resolution, 15 seconds) MR imaging examinations. Readers rated enhancement shape, enhancement distribution, border architecture, enhancement intensity, presence of rim enhancement or internal septations, and the shape of the contrast material kinetic curve. Regression was performed for each feature individually and after adjustment for associated mammographic findings. Multivariate models were also constructed from multiple architectural and dynamic features. Areas under the receiver operating characteristic curve (A z values) were estimated for all models. Results: There were 995 lesions in 854 women (mean age, 53 years Ϯ 12 [standard deviation]; range, 18 -80 years) for whom pathology data were available. The absence of enhancement was associated with an 88% negative predictive value for cancer. Qualitative characterization of the dynamic enhancement pattern was associated with an A z value of 0.66 across all lesion architectures. Focal mass margins (A z ϭ 0.76) and signal intensity (A z ϭ 0.70) were highly predictive imaging features. Multivariate models were constructed with an A z value of 0.880. Conclusion: Architectural and dynamic features are important in breast MR imaging interpretation. Multivariate models involving feature assessment have a diagnostic accuracy superior to that of qualitative characterization of the dynamic enhancement pattern

Integrative testis transcriptome analysis reveals differentially expressed miRNAs and their mRNA targets during early puberty in Atlantic salmon

Background: Our understanding of the molecular mechanisms implementing pubertal maturation of the testis in vertebrates is incomplete. This topic is relevant in Atlantic salmon aquaculture, since precocious male puberty negatively impacts animal welfare and growth. We hypothesize that certain miRNAs modulate mRNAs relevant for the initiation of puberty. To explore which miRNAs regulate mRNAs during initiation of puberty in salmon, we performed an integrated transcriptome analysis (miRNA and mRNA-seq) of salmon testis at three stages of development: an immature, long-term quiescent stage, a prepubertal stage just before, and a pubertal stage just after the onset of single cell proliferation activity in the testis. Results: Differentially expressed miRNAs clustered into 5 distinct expression profiles related to the immature, prepubertal and pubertal salmon testis. Potential mRNA targets of these miRNAs were predicted with miRmap and filtered for mRNAs displaying negatively correlated expression patterns. In summary, this analysis revealed miRNAs previously known to be regulated in immature vertebrate testis (miR-101, miR-137, miR-92b, miR-18a, miR-20a), but also miRNAs first reported here as regulated in the testis (miR-new289, miR-30c, miR-724, miR-26b, miR-new271, miR-217, miR-216a, miR-135a, miR-new194 and the novel predicted n268). By KEGG enrichment analysis, progesterone signaling and cell cycle pathway genes were found regulated by these differentially expressed miRNAs. During the transition into puberty we found differential expression of miRNAs previously associated (let7a/b/c), or newly associated (miR-15c, miR-2184, miR-145 and the novel predicted n7a and b) with this stage. KEGG enrichment analysis revealed that mRNAs of the Wnt, Hedgehog and Apelin signaling pathways were potential regulated targets during the transition into puberty. Likewise, several regulated miRNAs in the pubertal stage had earlier been associated (miR-20a, miR-25, miR-181a, miR-202, let7c/d/a, miR-125b, miR-222a/b, miR-190a) or have now been found connected (miR-2188, miR-144, miR-731, miR-8157 and the novel n2) to the initiation of puberty. Conclusions: This study has - for the first time - linked testis maturation to specific miRNAs and their inversely correlated expressed targets in Atlantic salmon. The study indicates a broad functional conservation of already known miRNAs and associated pathways involved in the transition into puberty in vertebrates. The analysis also reveals miRNAs not previously associated with testis tissue or its maturation, which calls for further functional studies in the testis