Budget impact analysis of gene expression tests to aid therapy decisions for breast cancer patients in Germany.

OBJECTIVES: Many women with early-stage, hormone receptor-positive breast cancer may not benefit from adjuvant chemotherapy. Gene expression tests can reduce chemotherapy over- and undertreatment by providing prognostic information on the likelihood of recurrence and, with Oncotype DX, predictive information on chemotherapy benefit. These tests are currently not reimbursed by German healthcare payers. An analysis was conducted to evaluate the budget impact of gene expression tests in Germany. MATERIALS AND METHODS: Costs of gene expression tests and medical and non-medical costs associated with treatment were assessed from healthcare payer and societal perspectives. Costs were estimated from data collected at a university hospital and were combined with decision impact data for Oncotype DX, MammaPrint, Prosigna and EndoPredict (EPclin). Changes in chemotherapy use and budget impact were evaluated over 1 year for 20,000 women. RESULTS: Chemotherapy was associated with substantial annual costs of EUR 19,003 and EUR 84,412 per therapy from the healthcare payer and societal perspective, respectively. Compared with standard care, only Oncotype DX was associated with cost savings to healthcare payers and society (EUR 5.9 million and EUR 253 million, respectively). Scenario analysis showed that both women at high clinical but low genomic risk and low clinical but high genomic risk were important contributors to costs. CONCLUSIONS: Oncotype DX was the only gene expression test that was estimated to reduce costs versus standard care in Germany. The reimbursement of Oncotype DX testing in standard clinical practice in Germany should be considered.

Evaluation of a Marker Clip System in Sonographically Guided Core Needle Biopsy for Breast Cancer Localization Before and After Neoadjuvant Chemotherapy.

Introduction The placement of intramammary marker clips has proven to be helpful for tumor localization in patients undergoing neoadjuvant chemotherapy and breast-conserving surgery. The purpose of our study was to investigate the feasibility of using a clip marker system for breast cancer localization and its influence on the imaging assessment of treatment responses after neoadjuvant chemotherapy. Patients and Methods Between March and June 2015, a total of 25 patients (n = 25), with a suspicion of invasive breast cancer with diameters of at least 2 cm (cT2), underwent preoperative sonographically guided core needle biopsy using a single-use breast biopsy system (HistoCore™) and intramammary clip marking using a directly adapted clip system based on the established O-Twist Marker™, before their scheduled preoperative neoadjuvant chemotherapy. Localization of the intramammary marker clip was controlled by sonography and digital breast tomosynthesis. Results Sonography detected no dislocation of intrammammary marker clips in 20 of 25 patients (80 %), while digital breast tomosynthesis showed accurate placement without dislocation in 24 patients (96 %) (p < 0.05). There was no evidence of significant clip migration during preoperative follow-up imaging after neoadjuvant chemotherapy. No complication related to the clip marking was noted and there was no difficulty in evaluating the treatment response to neoadjuvant chemotherapy. Among the breast-conserving surgeries performed, no cases were identified in which intraoperative loss of the marker clip had occurred. Conclusion Our study underscores the importance of intramammary marking clip systems before neoadjuvant chemotherapy. Placement of marker clips is advised to facilitate accurate tumor bed localization. With regard to digital breast tomosynthesis, its development continues to improve the quality of diagnostics and the therapy of breast cancer particularly for small breast cancer tumors or in neoadjuvant chemotherapy setting.

Time and Resources Needed to Document Patients with Breast Cancer from Primary Diagnosis to Follow-up - Results of a Single-center Study.

Aim: Certification of breast centers helps improve the quality of care but requires additional resources, particularly for documentation. There are currently no published data on the actual staff costs and financial resources required for such documentation. The aim of this study was to determine the time and resources required to document a patient with primary breast cancer from diagnosis to the end of follow-up, to establish a database for future strategic decisions. Material and Methods: All diagnostic and therapeutic procedures of patients with primary breast cancer were recorded at the University Breast Center of Franconia. All time points for documentation were evaluated using structured interviews. The times required to document a representative number of patients were determined and combined with the staff costs of the different professional groups, to calculate the financial resources required for documentation. Results: A total of 494 time points for documentation were identified. The study also identified 21 departments and 20 different professional groups involved in the documentation. The majority (54 %) of documentation was done by physicians. 62 % of all documentation involved outpatients. The results of different scenarios for the diagnosis, therapy and follow-up of breast cancer patients in a certified breast center showed that the time required for documentation can be as much as 105 hours, costing € 4135. Conclusion: This analysis shows the substantial staffing and financial costs required for documentation in certified centers. A multi-center study will be carried out to compare the costs for certified breast centers of varying sizes with the costs of non-certified care facilities.

Percent Mammographic Density and Dense Area as Risk Factors for Breast Cancer.

Purpose: Mammographic characteristics are known to be correlated to breast cancer risk. Percent mammographic density (PMD), as assessed by computer-assisted methods, is an established risk factor for breast cancer. Along with this assessment the absolute dense area (DA) of the breast is reported as well. Aim of this study was to assess the predictive value of DA concerning breast cancer risk in addition to other risk factors and in addition to PMD. Methods: We conducted a case control study with hospital-based patients with a diagnosis of invasive breast cancer and healthy women as controls. A total of 561 patients and 376 controls with available mammographic density were included into this study. We describe the differences concerning the common risk factors BMI, parital status, use of hormone replacement therapy (HRT) and menopause between cases and controls and estimate the odds ratios for PMD and DA, adjusted for the mentioned risk factors. Furthermore we compare the prediction models with each other to find out whether the addition of DA improves the model. Results: Mammographic density and DA were highly correlated with each other. Both variables were as well correlated to the commonly known risk factors with an expected direction and strength, however PMD (ρ = -0.56) was stronger correlated to BMI than DA (ρ = -0.11). The group of women within the highest quartil of PMD had an OR of 2.12 (95 % CI: 1.25-3.62). This could not be seen for the fourth quartile concerning DA. However the assessment of breast cancer risk could be improved by including DA in a prediction model in addition to common risk factors and PMD. Conclusions: The inclusion of the parameter DA into a prediction model for breast cancer in addition to established risk factors and PMD could improve the breast cancer risk assessment. As DA is measured together with PMD in the process of computer-assisted assessment of PMD it might be considered to include it as one additional breast cancer risk factor that is obtained from breast imaging.

Health Services Research and Health Economy - Quality Care Training in Gynaecology, with Focus On Gynaecological Oncology.

In the era of cost increases and reduced resources in the German healthcare system, the value of health services research and health economics is increasing more and more. Health services research attempts to develop concepts for the most effective ways to organise, manage, finance and deliver high-quality care and evaluates the implementation of these concepts with regard to daily routine conditions. Goals are the assessment of benefits and the economic advantages and disadvantages of new and established diagnostic methods, drugs and vaccines. Regarding these goals, it is clear that health services research goes hand in hand with health economics, which evaluates the benefits of diagnostic and therapeutic procedures in relation to the costs. Both scientific fields have focus principally on gynaecology and particularly on gynaecological oncology in Germany, as can be seen by numerous publications. These present several advantages compared with clinical trials - they uncover gaps in health care, question the material, staffing and consequently the financial resources required and they allow the estimation of value and the comparison of different innovations to identify the best options for our patients.

The era of centers: the influence of establishing specialized centers on patients' choice of hospital.

PURPOSE: It is considered that establishing accredited specialized centers can serve as a marketing tool. This study investigated whether accredited specialized centers influence patients' choice of hospital. METHODS: A total of 2,389 patients was included in a questionnaire survey: 468 at the Department of Gynecology, 745 at the certified University Breast Center of Franconia, 1,000 at the University Perinatal Center of Franconia and 176 for whom classification details were lacking. RESULTS: Among the oncological patients, physicians in private practice played an important role in the choice of hospital (58.4 vs. 25.7%; P < 0.001; OR 4.058). Among obstetric patients, the primary factors were recommendations from family [odds ratio (OR) 0.495], friends (OR 0.218), and previous personal experience of the hospital (OR 0.695). For oncological patients, treatment quality (OR 2.693), availability of a center (OR 1.785), and certification (OR 3.939) were comparatively more important. For obstetric patients, friendliness (OR 0.409) and attractive accommodation (OR 0.153) were more important. CONCLUSIONS: Physicians are the most important source of recommendations for oncological patients. From the marketing point of view, intensive involvement of local private-practice physicians is necessary. The availability of certified perinatal centers does not currently play any part in patients' choice of hospital.

Macrosomia: a new formula for optimized fetal weight estimation.

OBJECTIVES: To develop and test a specific formula for estimating weight in the macrosomic fetus. METHODS: Ultrasound estimations of fetal weight were carried out within 1 week of delivery in 424 singleton fetuses with a birth weight of > or = 4000 g. Exclusion criteria were multiple pregnancy, intrauterine death and major structural or chromosomal anomalies. Stepwise regression modeling was used to derive a prediction formula with birth weight as the dependent variable and maternal booking weight and fetal biometric measurements as independent parameters. After a new formula for estimated fetal weight (EFW) had been developed in a formula-finding group (n = 284), it was compared with commonly used weight equations (evaluation group, n = 140). RESULTS: The new formula (log(e)EFW = 7.6377445039 + 0.0002951035 x maternal weight + 0.0003949464 x head circumference + 0.0005241529 x abdominal circumference + 0.0048698624 x femur length) proved to be superior to established equations, with the smallest mean error (mean +/- SD, -10 +/- 202 g), the smallest mean percentage error (mean +/- SD, -0.03 +/- 4.6%) and the lowest mean absolute percentage error (3.69 (range, 0.05-13.57)%) when studied in the evaluation group. With the new formula, 77.9% of estimates fell within +/- 5% of the actual weight at birth, 97.1% within +/- 10%, and 100% within +/- 15% and +/- 20%. CONCLUSIONS: The new formula allows better weight estimation in the macrosomic fetus.

Single nucleotide polymorphism D1853N of the ATM gene may alter the risk for breast cancer.

PURPOSE: Various ATM (ataxia telangiectasia-mutated) mutations and polymorphisms have been reported to be associated with an increased breast cancer risk. Recent studies have produced contradictory results regarding the association between ATM genetic variants and breast cancer risk. MATERIALS AND METHODS: The common ATM polymorphism 5557G>A (p.D1853N) (rs1801516), previously suggested to be associated with bilateral breast cancer, was analyzed using real-time PCR in 514 unselected patients with breast cancer and 511 age-matched healthy control individuals. DNA was obtained from peripheral blood draw. RESULTS: The ATM genotype was weakly associated with the risk for breast cancer (P = 0.04 for the overall test). The odds ratio for women with a heterozygous genotype was 0.70 (95% CI, 0.52-0.94) and for the homozygous variant 0.63 (95% CI, 0.27-1.49). Disease-free survival and overall survival showed no significant association with specific genotypes. CONCLUSIONS: The results of this study might suggest a minor association between polymorphism 5557G>A and a reduced risk of breast cancer.

Fetal adrenal haemorrhage--two-dimensional and three-dimensional imaging.

A case of prenatal adrenal haemorrhage first detected by 2-dimensional and 3-dimensional sonography at 27 weeks' gestation is reported. Ultrasound examination showed a large cystic mass (32 x 27 x 27 mm) in the right suprarenal region of the fetus. Two weeks later, the mass had slightly increased in size demonstrating hyperechoic areas within the cyst. Further serial ultrasound examinations revealed a progressive organisation of the cystic mass associated with a moderate reduction in size. The diagnosis of adrenal haemorrhage was confirmed by postnatal follow-up sonograms as the mass decreased in size from 28 x 21 x 21 mm on day 1 to 23 x 18 x 17 mm on day 42. Course and sonographic signs were typical for adrenal haemorrhage and the neonate was therefore managed without surgical exploration. The child is developing normally at 6 months of age.

The invasion front of human colorectal adenocarcinomas shows co-localization of nuclear beta-catenin, cyclin D1, and p16INK4A and is a region of low proliferation.

At the invasion front of well-differentiated colorectal adenocarcinomas, the oncogene beta-catenin is found in the nuclear compartment of tumor cells. Under these conditions, beta-catenin can function as a transcription factor and thus activate target genes. One of these target genes, cyclin D1, is known to induce proliferation. However, invasion front of well-differentiated colorectal adenocarcinomas are known to be zones of low proliferation and express the cell cycle inhibitor p16INK4A. Therefore, we investigated the expression profiles of nuclear beta-catenin, cyclin D1, p16INK4A, and the Ki-67 antigen, a marker for proliferation, in serial sections of well-differentiated colorectal adenocarcinomas. Invasion fronts with nuclear beta-catenin were compared with areas from central parts of the tumors without nuclear beta-catenin, for the expression of cyclin D1, p16INK4A, and Ki-67. It was observed that expression of nuclear beta-catenin, cyclin D1, and p16INK4A at the invasion front are significantly correlated. Such areas exhibit low Ki-67 expression indicating a low rate of proliferation. Thus, in colorectal carcinogenesis the function of beta-catenin and its target gene cyclin D1 does not appear to be the induction of tumor cell proliferation. In particular, the function of cyclin D1 should be reconsidered in view of these observations.