Effect of mammography screening on surgical treatment for breast cancer in Norway: comparative analysis of cancer registry data

Objective To determine the effect of mammography screening on surgical treatment for breast cancer

Expression of thyroid transcription factor-1 is associated with a basal-like phenotype in breast carcinomas

Background: The differential diagnosis between primary and secondary breast cancers might be difficult, especially in poorly differentiated tumors. Thyroid Transcription Factor-1 (TTF-1) has been regarded as a reliable marker for lung or thyroid origin, with only occasional positive staining in other tumors. However, positive cases have recently been reported among primary breast carcinomas. Methods and results: Here, we analyzed expression of TTF-1 protein (clone SPT24) by immunohistochemical staining of sections from paraffin embedded tumor samples in 247 primary breast cancers from the population- based Norwegian Breast Cancer Screening Program. Positive staining (weak or strong) was observed in 7 cases (2,8%). As novel observations, positivity was demonstrated more frequently in estrogen receptor negative cases (14,0% vs. 1,4%; p = 0,004), highly proliferative tumors (8,8% vs. 1,1%; p = 0,008), tumors with a basal-like phenotype by showing expression of CK5/6 and/or P-cadherin (11,1% vs. 1,4%; p = 0,01), and tumors with blood vessel invasion (9,7% vs. 1,9%; p = 0,04). Also, TTF-1 was associated with histological grade 3 tumors compared with grade 1 or 2 tumors (7,7% vs. 1,5%; p = 0,04) as well as lymph node positive cases (5,2% vs. 1,8%; p = 0,03). Conclusions: Our population-based findings indicate that TTF-1 may be positive in approximately 3% of primary breast cancers, and positivity indicates an association with adverse prognostic factors

Additional file 1: Table S1. of Accuracy of cervical cytology: comparison of diagnoses of 100 Pap smears read by four pathologists at three hospitals in Norway

Diagnoses per pathologist (P2–P5) in samples with Normal cytology at UNN. Table S2. Diagnoses per pathologist (P2–P5) in samples with ASC-US cytology at UNN. Table S3. Diagnoses per pathologist (P2–P5) in samples with LSIL cytology at UNN. Table S4. Diagnoses per pathologist (P2–P5) in samples with ASC-H cytology at UNN. Table S5. Diagnoses per pathologist in samples with HSIL cytology at UNN. Figure S1. Distribution of high-grade cytology (ASC-H+) diagnoses by observer (P2–P5) in women with at least one high-grade cytology (N=61). Figure S2. Distribution of high-grade cytology (ASC-H+) diagnoses by observer (P2–P5) in women with histological CIN2+ in follow-up (N=32). (PDF 100 kb

“Evaluation of ROS1 expression and rearrangements in a large cohort of early-stage lung cancer”

Abstract Background ROS1 fusion is an infrequent, but attractive target for therapy in patients with metastatic non- small-cell lung cancer. In studies on mainly late-stage disease, the prevalence of ROS1 fusions is about 1–3%. In early-stage lung cancer ROS1 might also provide a fruitful target for neoadjuvant or adjuvant therapy. In the present study, we investigated the prevalence of ROS1 fusion in a Norwegian cohort of early-stage lung cancer. We also explored whether positive ROS1 immunohistochemical (IHC) stain was associated with certain mutations, clinical characteristics and outcomes. Methods The study was performed using biobank material from 921 lung cancer patients including 542 patients with adenocarcinoma surgically resected during 2006–2018. Initially, we screened the samples with two different IHC clones (D4D6 and SP384) targeting ROS1. All samples that showed more than weak or focal staining, as well as a subgroup of negative samples, were analyzed with ROS1 fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) with a comprehensive NGS DNA and RNA panel. Positive ROS1-fusion was defined as those samples positive in at least two of the three methods (IHC, FISH, NGS). Results Fifty cases were IHC positive. Of these, three samples were both NGS and FISH-positive and considered positive for ROS1 fusion. Two more samples were FISH positive only, and whilst IHC and NGS were negative. These were also negative with Reverse Transcription quantitative real time Polymerase Chain Reaction (RT-qPCR). The prevalence of ROS1 fusion in adenocarcinomas was 0.6%. All cases with ROS1 fusion had TP53 mutations. IHC-positivity was associated with adenocarcinoma. Among SP384-IHC positive cases we also found an association with never smoking status. There was no association between positive IHC and overall survival, time to relapse, age, stage, sex or pack-year of smoking. Conclusions ROS1 seems to be less frequent in early-stage disease than in advanced stages. IHC is a sensitive, but less specific method and the results need to be confirmed with another method like FISH or NGS

Interval and Consecutive Round Breast Cancer after Digital Breast Tomosynthesis and Synthetic 2D Mammography versus Standard 2D Digital Mammography in BreastScreen Norway

Background: Screening that includes digital breast tomosynthesis (DBT) with two-dimensional (2D) synthetic mammography (SM) or standard 2D digital mammography (DM) results in detection of more breast cancers than does screening with DM alone. A decrease in interval breast cancer rates is anticipated but is not reported. Purpose: To compare rates and characteristics of (a) interval breast cancer in women screened with DBT and SM versus those screened with DM alone and (b) screen-detected breast cancer at consecutive screenings with DM. Materials and Methods: This prospective cohort study from BreastScreen Norway included women screened with DBT and SM (study group) or DM alone (control group) between February 2014 and December 2015 (baseline). All women, except nonattendees, women with breast cancer, and those who exceeded the upper age limit, were consecutively screened with DM after 2 years. Interval breast cancer, sensitivity, and specificity were estimated for women screened at baseline. Recall, screen-detected breast cancer, and positive predictive value were analyzed for consecutively screened women. A χ2 test, t test (P < .001 after Bonferroni correction indicated a significant difference), and binomial regression model were used to analyze differences across groups. Results: A total of 92 404 women who underwent baseline screening (mean age, 59 years ± 6 [standard deviation]) were evaluated; 34 641 women in the study group (mean age, 59 years ± 6) were screened with DBT and SM and 57 763 women in the control group (mean age, 59 years ± 6) were screened with DM. A total of 26 474 women in the study group (mean age, 60 years ± 5) and 45 543 women in the control group (mean age, 60 years ± 5) were consecutively screened with DM. Rates of interval breast cancer were 2.0 per 1000 screened women in the study group and 1.5 per 1000 screened women in the control group (P = .12). No differences in histopathologic characteristics of interval breast cancer were observed. In the consecutive screening round, rates of screen-detected breast cancer were 3.9 per 1000 screened women (study group) and 5.6 per 1000 screened women (control group) (P = .001). Rates of histologic grade 1 invasive cancer were 0.5 per 1000 screened women (study group) and 1.3 per 1000 screened women (control group) (P = .001). Conclusion: No differences in interval breast cancer rates or tumor characteristics were observed in women screened with DBT and SM compared with women screened with DM. Higher rates of low-grade screen-detected tumors were observed in the control group at consecutive screening

Digital Breast Tomosynthesis and Synthetic 2D Mammography versus Digital Mammography: Evaluation in a Population-based Screening Program

Purpose: To compare the performance of digital breast tomosynthesis (DBT) and two-dimensional synthetic mammography (SM) with that of digital mammography (DM) in a population-based mammographic screening program. Materials and Methods: In this prospective cohort study, data from 37 185 women screened with DBT and SM and from 61 742 women screened with DM as part of a population-based screening program in 2014 and 2015 were included. Early performance measures, including recall rate due to abnormal mammographic findings, rate of screen-detected breast cancer, positive predictive value of recall, positive predictive value of needle biopsy, histopathologic type, tumor size, tumor grade, lymph node involvement, hormonal status, Ki-67 level, and human epidermal growth factor receptor 2 status were compared in women who underwent DBT and SM screening and in those who underwent DM screening by using x2 tests, two-sample unpaired t tests, and tests of proportions. Results: Recall rates were 3.4% for DBT and SM screening and 3.3% for DM screening (P = .563). DBT and SM screening showed a significantly higher rate of screen-detected cancer compared with DM screening (9.4 vs 6.1 cancers per 1000 patients screened, respectively; P , .001). The rate of detection of tumors 10 mm or smaller was 3.2 per 1000 patients screened with DBT and SM and 1.8 per 1000 patients screened with DM (P , .001), and the rate of grade 1 tumors was 3.3 per 1000 patients screened with DBT and SM versus 1.4 per 1000 patients screened with DM (P , .001). On the basis of immunohistochemical analyses, rates of lymph node involvement and tumor subtypes did not differ between women who underwent DBT and SM screening and those who underwent DM screening. Conclusion: DBT and SM screening increased the detection rate of histologically favorable tumors compared with that attained with DM screening