Awareness of Breast Cancer Risk Factors in Women with vs. Without High Breast Density.

Purpose: Women with high breast density (HBD) carry an increased risk for breast cancer (BC). The aim of the study was to provide data on awareness and knowledge gaps among women with vs w/o HBD about BC risk factors (BCRFs), which is the basis for effective communication about screening. Patients and Methods: This was a web-based survey of 3000 women aged ≥30 and ≤70 from six countries. It comprised of 45 questions. T-tests and chi-square tests with False Discovery Rate adjustments were conducted as applicable, with significant differences reported at α=0.05. Results: Three-thousand women were included in the analysis, 733 (24.4%) had HBD. Overall, 39% of women were familiar with the concept of HBD in the context of BC. Thirty-one percent of women were aware of HBD as BCRF and for 24% of women HBD was personally applicable. A significantly higher proportion of women with HBD were aware of almost all BCRFs compared to women w/o HBD (p ≤ 0.05). Similarly, a significantly higher proportion of women with HBD have undergone screening procedures compared to women w/o HBD (p ≤ 0.05). Women with HBD were significantly better aware of basic facts about BC (p ≤ 0.05). A total of 1617 women underwent mammography, 904 ultrasound and 150 MRI during their last screening. The most relevant source of information about BC was the health care professional, as reported by 63% of women. Conclusion: Overall 39% of women were familiar with HBD as BCRF. Lack of BCRF awareness may contribute to delayed screenings, missed opportunities for early detection, and potentially poorer outcomes for individuals with dense breast tissue. Thus, this information should be communicated more widely.

Iopromide for Contrast-Enhanced Mammography: A Systemic Review and Meta-Analysis of Pertinent Literature.

Background: Contrast-enhanced mammography (CEM) is an emerging breast imaging modality. Clinical data is scarce. Objectives: To summarize clinical evidence on the use of iopromide in CEM for the detection or by systematically analyzing the available literature on efficacy and safety. Design: Systematic review and meta-analysis. Data sources and methods: Iopromide-specific publications reporting its use in CEM were identified by a systematic search within Bayer's Product Literature Information (PLI) database and by levering a recent review publication. The literature search in PLI was performed up to January 2023. The confirmatory-supporting review publication was based on a MEDLINE/EMBASE + full text search for publications issued between September 2003 and January 2019. Relevant literature was selected based on pre-defined criteria by 2 reviewers. The comparison of CEM vs traditional mammography (XRM) was performed on published results of sensitivity and specificity. Differences in diagnostic parameters were assessed within a meta-analysis. Results: Literature search: A total of 31 studies were identified reporting data on 5194 patients. Thereof, 19 studies on efficacy and 3 studies on safety. Efficacy: in 11 studies comparing iopromide CEM vs XRM, sensitivity was up to 43% higher (range 1%-43%) for CEM. Differences in specificity were found to be in a range of -4% to 46% for CEM compared with XRM. The overall gain in sensitivity for CEM vs XRM was 7% (95% CI [4%, 11%]) with no statistically significant loss in specificity in any study assessed. In most studies, accuracy, positive predictive value, and negative predictive value were found to be in favor of CEM. In 2 studies comparing CEM with breast magnetic resonance imaging (bMRI), both imaging modalities performed either equally well or CEM tended to show better results with respect to sensitivity and specificity. Safety: eight cases of iopromide-related adverse drug reactions were reported in 1022 patients (0.8%). Conclusions: Pertinent literature provides evidence for clinical utility of iopromide in CEM for the detection or confirmation of breast cancer. The overall gain in sensitivity for iopromide CEM vs XRM was 7% with no statistically significant loss in specificity.

Sensitivity of Contrast-Enhanced Breast MRI vs X-ray Mammography Based on Cancer Histology, Tumor Grading, Receptor Status, and Molecular Subtype: A Supplemental Analysis of 2 Large Phase III Studies.

Background: The impact of certain tumor parameters on the sensitivity of imaging tools is unknown. The purpose was to study the impact of breast cancer histology, tumor grading, single receptor status, and molecular subtype on the sensitivity of contrast-enhanced breast magnetic resonance imaging (CE-BMRI) vs X-ray mammography (XRM) to detect breast cancer. Materials and Methods: We ran a supplemental analysis of 2 global Phase III studies which recruited patients with histologically proven breast cancers. The sensitivity of CE-BMRI vs XRM to detect cancer lesions with different histologies, tumor grading, single receptor status, and molecular subtype was compared. Six blinded readers for each study evaluated the images. Results were summarized as the "Mean Reader." For each reader, sensitivity was defined as the proportion of detected lesions vs the total number of lesions identified by the standard of reference. Two-sided 95% confidence intervals were calculated for within-group proportions, and for the difference between CE-BMRI and XRM, using a normal approximation to the binomial distribution. Results: In 778 patients, 1273 cancer lesions were detected. A total of 435 patients had 1 lesion, 254 had 2 lesions, and 77 had 3 or more lesions. The sensitivity of CE-BMRI was significantly higher compared with XRM irrespective of the histology. The largest difference was seen for invasive lobular carcinoma (22.3%) and ductal carcinoma in situ (19%). Across all 3 tumor grades, the sensitivity advantage of CE-BMRI over XRM ranged from 15.7% to 18.5%. Contrast-enhanced breast magnetic resonance imaging showed higher sensitivity compared with XRM irrespective of single receptor expressions (15.3%-19.4%). The sensitivities for both imaging methods were numerically higher for the more aggressive ER- (estrogen receptor), PR- (progesterone receptor), and HER2+ (human epidermal growth factor receptor 2) tumors. Irrespective of molecular subtype, sensitivity of CE-BMRI was 14.8% to 18.9% higher compared with XRM. Conclusions: Contrast-enhanced breast magnetic resonance imaging showed significantly higher sensitivity compared with XRM independent of tumor histology, tumor grading, single receptor status, and molecular subtype.Trial Registration: ClinicalTrials.gov: NCT01067976 and NCT01104584.

Immunohistochemical assessment of PD-L1 expression using three different monoclonal antibodies in triple negative breast cancer patients.

BACKGROUND: PD-L1 receptor expression in breast cancer tissue can be assessed with different anti-human PD-L1 monoclonal antibodies. The performance of three specific monoclonal antibodies in a head-to-head comparison is unknown. In addition, a potential correlation of PD-L1 expression and clinico-pathological parameters has not been investigated. METHODS: This was a retrospective study on tissue samples of patients with histologically confirmed triple negative breast cancer (TNBC). PD-L1 receptors were immune histochemically stained with three anti-human PD-L1 monoclonal antibodies: 22C3 and 28-8 for staining of tumor cell membranes (TC) and cytoplasm (Cyt), SP142 for immune cell staining (IC). Three different tissue samples of each patient were evaluated separately by two observers in a blinded fashion. The percentage of PD-L1 positive tumor cells in relation to the total number of tumor cells was determined. For antibodies 22C3 and 28-8 PD-L1 staining of 0 to < 1% of tumor cells was rated "negative", 1-50% was rated "positive" and > 50% was rated "strong positive". Cyt staining was defined as "negative" when no signal was observed and as "positive", when any positive signal was observed. For IC staining with SP142 all samples with PD-L1 expression ≥ 1% were rated as "positive". Finally, the relationship between PD-L1 expression and clinico-pathological parameters was analyzed. RESULTS: Tissue samples from 59 of 60 enrolled patients could be analyzed. Mean age was 55 years. Both the monoclonal antibodies 22C3 and 28-8 had similar properties, and were positive for both TC in 13 patients (22%) and for Cyt staining in 24 patients (40.7%). IC staining with antibody SP142 was positive in 24 patients (40.7%), who were also positive for Cyt staining. The differences between TC and Cyt staining and TC and IC staining were significant (p = 0.001). Cases with positive TC staining showed higher Ki67 expression compared to those with negative staining, 40 vs 30%, respectively (p = 0.05). None of the other clinico-pathological parameters showed any correlation with PDL1 expression. CONCLUSIONS: Antibodies 22C3 and 28-8 can be used interchangeably for PD-L1 determination in tumor cells of TNBC patients. Results for Cyt staining with 22C3 or 28-8 and IC staining with SP142 were identical. In our study PD-L1 expression correlates with Ki67 expression but not with OS or DFS.

Clinical Efficacy of Reduced-Dose Gadobutrol Versus Standard-Dose Gadoterate for Contrast-Enhanced MRI of the CNS: An International Multicenter Prospective Crossover Trial (LEADER-75).

BACKGROUND. Gadobutrol and gadoterate are widely used macrocyclic gadolinium-based contrast agents. Given gadobutrol's higher T1 relaxivity, a reduced gadobutrol dose should achieve essentially equivalent diagnostic efficacy as a standard dose of gadoterate. OBJECTIVE. The purpose of our study was to show efficacy of a 25% reduced dose of gadobutrol is noninferior to 100% standard dose of gadoterate for contrast-enhanced MRI of the CNS. METHODS. In this international prospective multicenter open-label crossover trial (LEADER-75 [Lower Administered Dose With Higher Relaxivity: Gadovist vs Dotarem]), adult patients with known or suspected CNS pathology underwent contrast-enhanced brain MRI with standard-dose gadoterate (0.1 mmol/kg); if an enhancing lesion was identified, a second MRI with reduced-dose gadobutrol (0.075 mmol/kg) was performed within 15 days of the first MRI. Three radiologists independently reviewed images to score three primary efficacy measures: subjective lesion enhancement, lesion border delineation, lesion internal morphology. A noninferiority analysis used readers' mean scores of the primary efficacy measures. Noninferiority of reduced-dose gadobutrol to standard-dose gadoterate for primary efficacy measures was defined as the difference in score between reduced-dose gadobutrol images and unenhanced images achieving at least 80% of the difference in score between standard-dose gadoterate images and unenhanced images. A post hoc analysis was performed to directly compare contrast-enhanced images for equivalence. Secondary efficacy variables included the number of lesions detected, reader confidence, diagnostic performance for malignancy, and reader preference in side-by-side comparison. RESULTS. The efficacy analysis included 141 patients (78 men, 63 women; mean age, 58.5 ± 13.5 [SD] years). Improvement of reduced-dose gadobutrol over unenhanced images was noninferior to improvement of standard-dose gadoterate over unenhanced images using a 20% noninferiority margin for all three primary efficacy measures using mean readings (p ≤ .025). In the post hoc analysis, the mean reading for the three primary efficacy measures differed by less than 1% between reduced-dose gadobutrol and standard-dose gadoterate, supporting equivalence of all measures using a narrow ± 5% margin (p ≤ .025). The total number of lesions detected by mean reading was 301 for reduced-dose gadobutrol versus 291 for standard-dose gadoterate. Mean reader confidence was 3.3 ± 0.6 for reduced-dose gadobutrol versus 3.3 ± 0.6 for standard-dose gadoterate. Sensitivity (58.7%), specificity (91.8%), and accuracy (70.2%) for malignancy from majority reading were identical for reduced-dose gadobutrol and standard-dose gadoterate. Reader preference was not different (95% CI, -0.10 to 0.11). CONCLUSION. A 25% reduced dose of gadobutrol is noninferior to standard-dose gadoterate for contrast-enhanced brain MRI. CLINICAL IMPACT. Use of reduced-dose gadobutrol should be considered for brain MRI, particularly in patients undergoing multiple contrast-enhanced examinations. TRIAL REGISTRATION. ClinicalTrials.gov NCT03602339; EU Clinical Trials Register EudraCT 2018-00690-78.

Diagnostic efficacy of contrast-enhanced breast MRI versus X-ray mammography in women with different degrees of breast density.

BACKGROUND: Detection of breast cancer in women with high breast densities is a clinical challenge. PURPOSE: To study the influence of different degrees of breast density on the sensitivity of contrast-enhanced breast magnetic resonance imaging (CE-BMRI) versus X-ray mammography (XRM). MATERIAL AND METHODS: We performed an additional analysis of two large Phase III clinical trials (G1; G2) which included women with histologically proven breast cancers, called "index cancers." Additional cancers were detected during image reading. We compared the sensitivity of CE-BMRI and XRM in women with different breast densities (ACR A→D; Version 5). For each study, six blinded readers evaluated the images. Results are given as the "Median Reader." RESULTS: A total of 774 patients were included, 169 had additional cancers. While sensitivity of CE-BMRI for detecting all index cancers was independent of breast density (ACR A→D) (G1: 83%→83%; G2: 91%→91%) the sensitivity of XRM declined (ACR A→D) (G1: 79%→62%; G2: 82%→64%). Thus, the sensitivity difference between both imaging modalities in ACR A breasts of 3% (G1) and 9% (G2) increased to 21% (G1) and 26% (G2) in ACR D breasts. Sensitivity of CE-BMRI for detecting at least one additional cancer increased with increasing breast density (ACR A→D) (G1: 50%→73%, G2: 57%→81%). XRM's sensitivity decreased (G1: 34%→20%) or remained stable (G2: 24%→25%). CONCLUSION: CE-BMRI showed significantly higher sensitivity compared to XRM.

Is vimentin a potential prognostic factor for patients with triple-negative breast cancer?

OBJECTIVE: To evaluate the prognostic potential of vimentin, p53, EGFR, CK5/6, CK 14, and CK 17 in patients with triple-negative breast cancer (TNBC). MATERIAL AND METHODS: Tumor specimens of 60 patients with histologically confirmed TNBC were retrospectively analyzed. Formalin-fixed paraffin-embedded blocks of the tumor tissue were used to prepare tissue microarrays (TMAs). After immune-histochemical staining, protein expression of vimentin, p53, EGFR, CK5/6, CK 14, and CK 17 was determined and the immunoreactive score (IRS) was calculated. The protein expression was correlated to overall (OS) and disease-free survival (DFS). RESULTS: Ninety percent of patients suffered from an invasive ductal carcinoma T1 or T2, 66.7% were N0, and 70% had a G3 tumor with Ki67 of > 14%. Vimentin expression was found in 28/60 patients (46.7%), p53 expression in 30/60 patients (50%), and EGFR expression in 3/60 patients (5%). CK5/6, CK14, and CK17 expression was found in 60.0%, 63.3%, and 66.7%, respectively. Vimentin expression vs no expression was associated with significantly higher mean Ki67 values (52.5% vs. 31.1%; p = 0.0013) and significantly higher p53 expression (67.9% vs. 34.4%; p = 0.0097). No significant association between vimentin expression and OS (p = 0.7710) or DFS (p = 0.5558) was found during a mean follow-up of 92 months. CONCLUSION: None of the six proteins proved to be suitable prognostic factors for OS and DSF in patients with TNBC.

Impact of body mass index, smoking habit, alcohol consumption, physical activity and parity on disease course of women with triple-negative breast cancer.

OBJECTIVE: To evaluate the potential impact of body mass index (BMI), smoking habit, alcohol consumption, physical activity and parity on disease course of women with triple-negative breast cancer (TNBC). MATERIAL AND METHODS: This was a retrospective chart analysis of patients with TNBC. Primary target parameters were overall survival (OS) and disease-free survival (DFS) depending on BMI, smoking habit, alcohol consumption, physical activity and parity. Results were descriptively evaluated and plotted as Kaplan-Meier curves. The null hypothesis was tested using the non-parametric log-rank test. All patients were treated at the University Medical School of Saarland, Dept of Gynecology, Obstetrics and Reproductive Medicine. RESULTS: A total of 197 patients were analyzed. More than 50% of women were 40-60 years old (mean 57 years) and had a normal BMI. More than 88% of patients had either a T1 or T2 tumor, 64% were N0 and 66.5% had a G3 cancer. Thirty-four of 84 patients (40.38%) on neo-adjuvant chemotherapy reached a pathology-confirmed complete remission. During the follow-up (median 41.43 months), 34 (17.3%) patients had recurrent disease and 51 (25.9%) suffered from metastases. A total of 51 (25.9%) finally deceased. OS and DFS were not significantly impacted by BMI (OS: p = 0.4720; DFS: p = 0.2272), smoking habit (p = 0.9892; p = 0.6040), alcohol consumption (p = 0.6515; p = 0.7460), physical activity (p = 0.3320; p = 0.5991) or parity (p = 0.5929; 0.1417). CONCLUSION: BMI, smoking habit, alcohol consumption, physical activity and parity had no impact on OS or DFS in women with TNBC.

Muscle mass loss in patients with metastatic breast cancer.

PURPOSE: To assess the change of body mass index (BMI), muscle mass, visceral and subcutaneous fat in patients with metastatic breast cancer. METHODS: In this retrospective chart analysis, patients with metastatic breast cancer as initial diagnosis between 2012 and 2016 were analyzed. Patients had received either chemotherapy (CTH) or endocrine therapy (ETH) according to the German S3 Guideline. BMI was calculated from the patients' weight and height. Change of muscle mass, visceral and subcutaneous fat was determined by comparing the surface area of these tissues on transverse CT images at the level of the third lumbar vertebrae (L3) at baseline and during treatment. RESULTS: A total of 45 patients were included in the study, 29 on CTH and 16 on ETH. BMI, visceral and subcutaneous fat remained stable over time for both treatment groups. When taking both treatment groups together, muscle mass decreased significantly by 5.0 ± 2.5 cm2 per year (p < 0.05). CONCLUSION: In patients with metastatic breast cancer, a slight reduction of muscle mass was observed, independent of therapy regimes.

Diagnostic Efficacy and Safety of Gadoxetate Disodium vs Gadobenate Dimeglumine in Patients With Known or Suspected Focal Liver Lesions: Results of a Clinical Phase III Study.

PURPOSE: The aim of this study is to evaluate the diagnostic efficacy and safety of gadoxetate disodium vs gadobenate dimeglumine in patients with known or suspected focal liver lesions. METHODS: This was a prospective, multicenter, double-blind, randomized, inter-individual Phase III study. The primary target-technical efficacy-was already published. Here, secondary efficacy parameters-sensitivity and specificity-and safety in specific patient populations are presented. Patients with suspected or known focal liver lesions scheduled for contrast-enhanced liver magnetic resonance imaging (MRI) were recruited and categorized in 4 a priori specified subgroups: (1) all patients, (2) patients with liver cancer (hepatocellular carcinoma [HCC]), (3) patients with cirrhosis, and (4) patients with HCC + cirrhosis. Dual multi-detector liver computed tomography (CT) served as standard of reference. RESULTS: A total of 295 patients were included. While the overall increase in sensitivity across all 4 patient groups was comparable for gadoxetate disodium (increase from pre- to post-contrast ranging from 6.2% to 9.9%) and gadobenate dimeglumine (ranging from -2.9% to 10.0%), significant differences were seen for some of the subgroups. There was a significantly higher increase in sensitivity for gadoxetate disodium in patients with HCC (7%) and HCC + cirrhosis (12.8%) in comparison with gadobenate dimeglumine. Specificity decreased for both agents: gadoxetate disodium by -2.8% to -6.3% and gadobenate dimeglumine by -3.3% to -8.7%. Gadoxetate showed a significantly lower loss of specificity in all subgroups. Safety was comparable in both groups. CONCLUSIONS: Gadoxetate disodium proved to be an effective liver-specific MRI contrast agent. Some distinct advantages over gadobenate dimeglumine were demonstrated in patients with HCC and patients with HCC + liver cirrhosis for sensitivity and specificity in liver lesion detection.

Post-marketing surveillance of gadobutrol for contrast-enhanced magnetic resonance imaging in Japan.

PURPOSE: To evaluate the safety of gadobutrol for magnetic resonance imaging in a prospective, non-interventional, post-marketing surveillance in Japan. MATERIALS AND METHODS: Gadobutrol was administered in accordance with Japanese prescribing information over a 2-year enrollment period, using a standardized questionnaire to collect information. The primary outcome was the incidence of adverse reactions (ARs) following gadobutrol injection. RESULTS: Questionnaire data were analyzed for 3337 patients (age, 58.1 ± 17.4 years [mean±SD]). Gadobutrol was administered at a dose of 0.10 ± 0.02 mL/kg body weight. Thirty-three patients were observed to have 42 ARs suspected to be due to gadobutrol, an incidence proportion of 0.99%; 29 ARs were acute (<1 h post-injection)-including one case of severe acute AR (0.03%). Patient subpopulations (with hepatic, renal, cardiovascular diseases) did not differ markedly in AR proportions categorized by age, sex, presence of comorbidity, or imaging indication. No cases of nephrogenic systemic fibrosis were reported. Investigators rated images as improved or profoundly improved following gadobutrol injection in 91.1% of examinations. CONCLUSION: Gadobutrol was well tolerated with a good safety profile in this post-marketing surveillance of a large patient population in Japan.

Her2-neu score as a prognostic factor for outcome in patients with triple-negative breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC) is characterized by a strong heterogeneity with regard to tumour biology as well as in the clinical course of the disease. This study aimed to analyse whether there are any prognostic factors enabling prediction of the clinical outcome in patients with TNBC. Particularly, the impact of Her2-neu score 0 versus Her2-neu score 1 and 2 on survival was investigated. MATERIALS AND METHODS: We retrospectively studied a cohort of 1013 patients with TNBC, diagnosed at seven hospitals between May 2002 and February 2015. We studied the impact of Her2-neu scores (0 vs. 1 or 2 with negative FISH) on disease-free survival (DFS) and overall survival (OS). RESULTS: 1013 patients were included in this study. 447 (44.13 %) of them had a T2-4 tumour. A total of 314 (31.00 %) were nodal-positive and 714 (70.48 %) had high-grade tumours. The Her2-neu score of all participating patients was determined. 588 (58.05 %) of them had a Her2-neu score 0, and 425 (41.95 %) had a score of 1 or 2. This study shows that TNBC patients with a Her2-neu score 0 had a significantly poorer outcome regarding DFS (p = 0.0001) and OS (p = 0.0051) compared to a score of 1 or 2. In contrast, grading did not seem to have any prognostic value for women with TNBC. CONCLUSION: The Her2-neu score 0 might be considered as an innovative prognostic factor for patients with TNBC indicating poor clinical outcome.

Safety of gadoxetate disodium: Results from the clinical phase II-III development program and postmarketing surveillance.

PURPOSE: To summarize the safety data of gadoxetate disodium, reported in 12 Phase II and III clinical development studies and in the postmarketing surveillance database. MATERIALS AND METHODS: Patients with liver lesions received gadoxetate disodium-enhanced liver magnetic resonance imaging (MRI). Adverse events (AEs) were recorded and evaluated with regard to a potential drug relationship. Subgroup analyses were run on patients with special medical history. Worldwide spontaneous AEs and adverse drug reactions (ADRs) from postmarketing safety surveillance were analyzed. RESULTS: A total of 1989 patients were included in the clinical development program. A total of 1581/1989 (79.5%) patients received the finally approved dose of 0.025 mmol/kg body weight. 10.1% of patients reported AEs, 4.1% were classified as related AEs. Nausea and headache were the most frequently reported related AEs, with 1.1% each. Age, history of contrast media allergy, liver cirrhosis, or impaired liver or renal function did not significantly impact the frequency and type of AEs. The postmarketing safety surveillance database encompassed more than 2.2 million patients. Nausea was the most frequent ADR, with a reporting rate of 0.00652%; all other symptoms were below 0.004%. CONCLUSION: Gadoxetate disodium for liver MRI has an excellent safety profile.

Different Pearl Indices in studies of hormonal contraceptives in the United States: impact of study population.

OBJECTIVE: To examine the impact of subject characteristics on efficacy as measured by the Pearl Index (PI) in clinical trials and to make study populations similar by matching. METHODS: Our analysis used US data from four large Phase III studies. We compared results from one fertility control patch study with pooled data from three studies with virtually identical design on oral hormonal contraceptives. First, we identified three characteristics that had the most impact on the PI. Second, we used these three variables and matched subjects from the patch study with those from the oral contraceptive (OC) studies. Finally, we calculated the PIs for matched and unmatched subjects from both the patch study and the OC studies. RESULTS: A total of 3706 subjects were included in our analysis. The variables 'Hispanic ethnicity', 'previous pregnancy' and 'previous use of hormonal contraceptives' had the most impact on the PI. The PIs for the matched patch cohort and the matched OC cohort were 2.97 and 2.48, respectively. Those for the unmatched patch cohort and the unmatched OC cohort were 10.17 and 0.90, respectively. CONCLUSION: Subject characteristics strongly influence the PI in clinical studies of hormonal contraceptives. In particular, Hispanic ethnicity, previous pregnancies and no previous use of hormonal contraceptives result in a higher PI. IMPLICATIONS: PIs from different clinical trials cannot be meaningfully compared unless subject characteristics that have most impact on the PI are similar or are made to be similar statistically as we did here by matching.

Axillary ultrasound for breast cancer staging: an attempt to identify clinical/histopathological factors impacting diagnostic performance.

AIM: To assess the diagnostic value of pre-surgery axillary ultrasound for nodal staging in patients with primary breast cancer and to identify clinical/histopathological factors impacting diagnostic performance. STUDY DESIGN: Single-center, retrospective chart analysis. We assessed sensitivity, specificity, and positive and negative predictive value of clinical examination as well as axillary ultrasound vs. clinical examination alone. The histopathological results were the standard of truth. In addition, we analyzed clinical and histopathological factors regarding their potential to impact sensitivity and specificity. RESULTS: We enrolled a total of 172 women in the study. Sensitivity of clinical examination plus ultrasound was significantly higher than for clinical examination alone (58% vs. 31.6%). Specificity and positive predictive value were similar while the negative predictive value increased from 63.4% to 73% when additionally applying ultrasound. Sensitivity and specificity of axillary ultrasound were impacted by tumor size (P = 0.2/0.04), suspicious axillary palpation (P < 0.01/<0.01), number of affected lymph nodes (P < 0.01/-) and distant metastases (P = 0.04/<0.01). All other factors had no impact. CONCLUSION: Since pre-surgery axillary nodal staging is currently used to determine disease management, axillary ultrasound is a useful add-on tool in the diagnostic armamentarium for breast cancer patients. Tumor size, suspicious axillary palpation, number of affected lymph nodes and distant metastases increase diagnostic performance of this diagnostic modality.

Pituitary, ovarian and additional contraceptive effects of an estradiol-based combined oral contraceptive: results of a randomized, open-label study.

BACKGROUND: The estrogen step-down/progestogen step-up 28-day estradiol valerate/dienogest (E(2)V/DNG) oral contraceptive effectively inhibits ovulation; however, limited data are available regarding its effects on estradiol (E2), progesterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) or its additional extraovarian contraceptive effects. STUDY DESIGN: In this secondary analysis, 100 women received E(2)V 3 mg on days 1-2, E(2)V 2 mg/DNG 2 mg on days 3-7, E(2)V 2 mg/DNG 3 mg on days 8-24, E(2)V 1 mg on days 25-26 and placebo on days 27-28 for one treatment cycle. Measures included the presence/absence of cervical mucus; endometrial thickness; and serum E2, progesterone, and gonadotropin levels. RESULTS: E2, progesterone, LH and FSH levels did not exhibit the typical ovulatory increase and remained relatively stable during the cycle. E(2)V/DNG reduced mean maximal endometrial thickness and proportion of women with visible cervical mucus. All parameters returned to pretreatment levels during the posttreatment cycle. CONCLUSION: E(2)V/DNG provides extraovarian contraceptive effects (reducing endometrial thickness and cervical mucus production) in addition to inhibiting ovulation, assuring contraceptive efficacy.

Chromosomal abnormalities in fetuses with ultrasonographically detected neural tube defects.

We analyzed the karyotype of fetuses with ultrasonographically detected neural tube defects (NTDs). In our study, we included a total of 194 fetuses with NTDs. We analyzed the type of NTD, the karyotype, maternal age, fetal gestational age at diagnosis, and fetal sex. Of the 194 fetuses with NTDs, 87 were anencephalic and 107 had other, nonanencephalic, NTDs. A total of 12 fetuses were shown to have chromosomal abnormalities. Three of 87 anencephalic fetuses (3.45%) had chromosomal abnormalities. The sex ratio for anencephalic fetuses was 65.5% : 34.5% for female and male fetuses. Nine of 107 fetuses with other NTDs (8.41%) had chromosomal abnormalities. Seven fetuses had isolated NTDs and a further seven fetuses had additional ultrasonographic anomalies. Two of the latter had abnormal karyotypes. The sex ratio of all other NTD cases was 67.3% : 32.7% for female and male fetuses. The high number of chromosomal abnormalities justifies prenatal karyotyping in all fetuses with ultrasonographically diagnosed NTDs.

A Canadian, multicentre study comparing the efficacy of a levonorgestrel-releasing intrauterine system to an oral contraceptive in women with idiopathic menorrhagia.

OBJECTIVES: To evaluate the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) compared with a combined oral contraceptive containing 1 mg norethindrone acetate and 20 mg ethinyl estradiol (OC1/20) in reducing menstrual blood loss (MBL) in women with idiopathic menorrhagia. METHODS: A prospective, randomized, open-label study was conducted in nine centres in Canada. Healthy women over 30 years of age suffering from idiopathic menorrhagia were treated either with LNG-IUS (n = 20) or with OC1/20 (n = 19) over 12 months. The primary endpoint was the change in MBL from baseline to 12 months. Secondary endpoints included treatment success (defined as a MBL score < 100 after 12 months), hemoglobin levels, and the menorrhagia severity score. RESULTS: In both treatment groups, MBL decreased significantly from baseline to 12 months (P < 0.001). For the primary endpoint, the MBL score decreased significantly more in the LNG-IUS group (median from 228 to 13, mean percent change-83%) compared to the OC1/20 group (median from 290 to 72; mean percent change-68%) (P = 0.002) after 12 months. In the LNG-IUS group, 80% of subjects had treatment success compared with 36.8 % in the OC1/20 group (P < 0.009). Both treatments increased hemoglobin concentrations significantly between baseline and 12 months. The menorrhagia severity score was consistently lower in the LNG-IUS group at all study time points and was significantly lower (P = 0.045) at six months. Both treatments were well tolerated. CONCLUSION: Both the LNG-IUS and the combined oral contraceptive effectively decreased menstrual blood loss in women with idiopathic menorrhagia. The overall clinical benefit was more pronounced with LNG-IUS than with OC1/20.

Ovulation inhibition with four variations of a four-phasic estradiol valerate/dienogest combined oral contraceptive: results of two prospective, randomized, open-label studies.

BACKGROUND: Attempts to improve the tolerability of combined oral contraceptives (COCs) have included the substitution of ethinylestradiol (EE) with 17beta-estradiol (E2). However, this has proved unsatisfactory, specifically in terms of cycle control. To improve upon the poor cycle control seen previously, E2 [in the form of estradiol valerate (E2V); 1 mg of E2V contains 0.76 mg of E2] was combined with dienogest (DNG) in a novel four-phasic regimen. In the current studies, the ovulation-inhibition potency of four variations of this regimen was assessed. STUDY DESIGN: Two randomized, open-label, Phase II studies were performed. The first study compared two regimens (Regimens 1A and 2A) with similar dosages of DNG but different lengths of application. Having established in Study 1 that the length of application of Regimen 2A was most suitable, but that the dosages of DNG were too low for effective ovulation inhibition, a second study, which compared two regimens (Regimens 2B and 2C) with similar lengths of application but with increased dosages of DNG, was undertaken. The primary efficacy variable in both studies was the proportion of women with a Hoogland score of 5 or 6 during Cycle 2. RESULTS: The full analysis set comprised 192 and 203 women in Studies 1 and 2, respectively. In Study 1, 10 women (10.9%) in Regimen 1A and 6 women (6.4%) in Regimen 2A had a Hoogland score of 5 or 6. In Study 2, three women (3.1%) in Regimen 2B and one woman (1.0%) in Regimen 2C had a Hoogland score of 5 or 6. There were no safety concerns with any of the regimens. CONCLUSION: The results of these studies identified a four-phasic COC preparation comprising E2V/DNG that provides efficient ovulation inhibition. It is expected that this regimen will lead to an innovative COC containing E2 instead of EE.