Macromastia: an economic burden? A disease cost analysis based on real-world data in Germany.

PURPOSE: Symptomatic macromastia causes physical and psychological problems that can lead to restrictions in the patients' social and working lives and a reduced quality of life. Associated medical treatments also have a considerable impact on health-care costs. Several studies have assessed these costs, but the total disease costs of macromastia have never been evaluated on the basis of real-world data. METHODS: The data for 76 patients who underwent reduction mammoplasty between 2008 and 2016 were collected using a two-part questionnaire (preoperative and postoperative), as well as the patient files. Topics surveyed, besides demographic data, included physician visits, medical imaging, medical procedures, medical treatments, rehabilitation and convalescent measures, drug intake, medical aids, exercise activity, and sick leave days before surgery, to calculate the costs per year of conservative treatment of symptomatic macromastia. RESULTS: The mean time from start of symptoms to surgery was 11.82 years. The data for this group of patients with symptomatic macromastia show that costs per patient amount to €1677.55 per year. These costs include medical consultation, radiological imaging, medical treatments and procedures, physical therapy and rehabilitation, medication, special brassieres, exercise classes costs for sick leave due to problems with macromastia, and travel expenses. CONCLUSIONS: These results show that considerable health-care costs arise due to macromastia with conservative treatment. Overall, macromastia costs €1677.55 per patient/year. In particular, lost productivity due to sick days and the costs of physiotherapy are factors driving the high costs.

Breast MRI texture analysis for prediction of BRCA-associated genetic risk.

BACKGROUND: BRCA1/2 deleterious variants account for most of the hereditary breast and ovarian cancer cases. Prediction models and guidelines for the assessment of genetic risk rely heavily on criteria with high variability such as family cancer history. Here we investigated the efficacy of MRI (magnetic resonance imaging) texture features as a predictor for BRCA mutation status. METHODS: A total of 41 female breast cancer individuals at high genetic risk, sixteen with a BRCA1/2 pathogenic variant and twenty five controls were included. From each MRI 4225 computer-extracted voxels were analyzed. Non-imaging features including clinical, family cancer history variables and triple negative receptor status (TNBC) were complementarily used. Lasso-principal component regression (L-PCR) analysis was implemented to compare the predictive performance, assessed as area under the curve (AUC), when imaging features were used, and lasso logistic regression or conventional logistic regression for the remaining analyses. RESULTS: Lasso-selected imaging principal components showed the highest predictive value (AUC 0.86), surpassing family cancer history. Clinical variables comprising age at disease onset and bilateral breast cancer yielded a relatively poor AUC (~ 0.56). Combination of imaging with the non-imaging variables led to an improvement of predictive performance in all analyses, with TNBC along with the imaging components yielding the highest AUC (0.94). Replacing family history variables with imaging components yielded an improvement of classification performance of ~ 4%, suggesting that imaging compensates the predictive information arising from family cancer structure. CONCLUSIONS: The L-PCR model uncovered evidence for the utility of MRI texture features in distinguishing between BRCA1/2 positive and negative high-risk breast cancer individuals, which may suggest value to diagnostic routine. Integration of computer-extracted texture analysis from MRI modalities in prediction models and inclusion criteria might play a role in reducing false positives or missed cases especially when established risk variables such as family history are missing.

Introducing multiple-choice questions to promote learning for medical students: effect on exam performance in obstetrics and gynecology.

PURPOSE: Testing is required in medical education. The large number of exams that students face requires effective learning strategies. Various methods of improving knowledge retention and recall have been discussed, two of the most widely evaluated of which are test-enhanced learning and pause procedures. This study investigated the effect of voluntary multiple-choice questions on students' performance. METHODS: In a prospective study from April 2013 to March 2015, 721 students were randomly assigned to receive supplementary online material only (control group) or additional multiple-choice questions (investigative group) accompanying lectures. Their performance in the final exam was evaluated. RESULTS: A total of 675 students were ultimately included, with 299 randomly assigned to the investigative group and 376 to the control group. Students in the investigative group scored significantly better in relation to grades and points (2.11 vs. 2.49; 33 vs 31.31; p < 0.05). The effect declined over time. CONCLUSION: This is the first study of the use of voluntary multiple-choice questions to improve medical students' performance. The results support test-enhanced learning and the feasibility of implementing multiple-choice questions in lectures.

Prognostic effect of Ki-67 in common clinical subgroups of patients with HER2-negative, hormone receptor-positive early breast cancer.

PURPOSE: Several clinical trials have investigated the prognostic and predictive usefulness of molecular markers. With limited predictive value, molecular markers have mainly been used to identify prognostic subgroups in which the indication for chemotherapy is doubtful and the prognosis is favorable enough for chemotherapy to be avoided. However, limited information is available about which groups of patients may benefit from additional therapy. This study aimed to describe the prognostic effects of Ki-67 in several common subgroups of patients with early breast cancer. METHODS: This retrospective study analyzed a single-center cohort of 3140 patients with HER2-, hormone receptor-positive breast cancer. Five-year disease-free survival (DFS) rates were calculated for low (< 10%), intermediate (10-19%), and high (≥ 20%) Ki-67 expression levels, as assessed by immunohistochemistry, and for subgroups relative to age, body mass index, disease stage, tumor grade, and (neo-)adjuvant chemotherapy. It was also investigated whether Ki-67 had different effects on DFS in these subgroups. RESULTS: The 5-year DFS rates for patients with low, intermediate, and high levels of Ki-67 expression were 0.90, 0.89, and 0.77, respectively. Ki-67 was able to further differentiate patients with an intermediate prognosis into different prognostic groups relative to common clinical parameters. Patients with stage II breast cancer had 5-year DFS rates of 0.84, 0.88, and 0.79 for low, intermediate, and high levels of Ki-67 expression. Ki-67 had different prognostic effects in subgroups defined by age and tumor grade. CONCLUSIONS: Ki-67 may help identify patients in intermediate prognostic groups with an unfavorable prognosis who may benefit from further therapy.

Association between breast cancer risk factors and molecular type in postmenopausal patients with hormone receptor-positive early breast cancer.

PURPOSE: Evidence shows that genetic and non-genetic risk factors for breast cancer (BC) differ relative to the molecular subtype. This analysis aimed to investigate associations between epidemiological risk factors and immunohistochemical subtypes in a cohort of postmenopausal, hormone receptor-positive BC patients. METHODS: The prospective, single-arm, multicenter phase IV PreFace study (Evaluation of Predictive Factors Regarding the Effectivity of Aromatase Inhibitor Therapy) included 3529 postmenopausal patients with hormone receptor-positive early BC. Data on their epidemiological risk factors were obtained from patients' diaries and their medical histories. Data on estrogen receptor, progesterone receptor, and HER2 receptor status were obtained from pathology reports. Patients with incomplete information were excluded. Data were analyzed using conditional inference regression analysis, analysis of variance, and the chi-squared test. RESULTS: In a cohort of 3392 patients, the strongest association with the molecular subtypes of BC was found for hormone replacement therapy (HRT) before diagnosis of early BC. The analysis showed that patients who took HRT at diagnosis had luminal A-like BC more often (83.7%) than those who had never taken HRT or had stopped taking it (75.5%). Luminal B-like BC and HER2-positive BC were diagnosed more often in women who had never taken HRT or had stopped taking it (13.3% and 11.2%, respectively) than in women who were taking HRT at diagnosis of BC (8.3% and 8.0%, respectively). CONCLUSIONS: This analysis shows an association between HRT and the distribution of molecular subtypes of BC. However, no associations between other factors (e.g., age at diagnosis, body mass index, smoking status, age at menopause, number of deliveries, age at first delivery, breastfeeding history, or family history) were noted.

BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients.

PURPOSE: BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. METHODS: Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. RESULTS: Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. CONCLUSIONS: BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.

Initial clinical results with a fusion prototype for mammography and three-dimensional ultrasound with a standard mammography system and a standard ultrasound probe.

BACKGROUND: Combinations *Equal contributors. of different imaging techniques in fusion devices appear to be associated with improvements in diagnostic assessment. PURPOSE: The aim of this study was to test the feasibility of using an automated standard three-dimensional (3D) ultrasound (US) device fused with standard mammography for the first time in breast cancer patients. MATERIAL AND METHODS: Digital mammograms and 3D automated US images were obtained in 23 patients with highly suspicious breast lesions. A recently developed fusion machine consisting of an ABVS 3D US transducer from an Acuson S2000 machine and a conventional Mammomat Inspiration device (both Siemens Healthcare GmbH, Erlangen, Germany) were used for the purpose. The feasibility of the examinations, imaging coverage, and patients' experience of the procedure were examined. RESULTS: In 15 out of 19 patients, the region of interest (ROI) with the tumor marked in the mammogram was visible on US. The examination was experienced positively by the patients, with no unexpected pain or injury. The examination was time-saving and well tolerated. CONCLUSION: In conclusion, we have shown initial clinical feasibility of an US/radiography fusion prototype with good localization and evaluation of the ROIs. The combined examination was well tolerated. The simultaneous evaluation with mammography and US imaging may be able to improve detection and reduce examiner-related variability.

Association between mammographic density and pregnancies relative to age and BMI: a breast cancer case-only analysis.

PURPOSE: Percentage mammographic density (PMD) is a major risk factor for breast cancer (BC). It is strongly associated with body mass index (BMI) and age, which are themselves risk factors for breast cancer. This analysis investigated the association between the number of full-term pregnancies and PMD in different subgroups relative to age and BMI. METHODS: Patients were identified in the breast cancer database of the University Breast Center for Franconia. A total of 2410 patients were identified, for whom information on parity, age, and BMI, and a mammogram from the time of first diagnosis were available for assessing PMD. Linear regression analyses were conducted to investigate the influence on PMD of the number of full-term pregnancies (FTPs), age, BMI, and interaction terms between them. RESULTS: As in previous studies, age, number of FTPs, and BMI were found to be associated with PMD in the expected direction. However, including the respective interaction terms improved the prediction of PMD even further. Specifically, the association between PMD and the number of FTPs differed in young patients under the age of 45 (mean decrease of 0.37 PMD units per pregnancy) from the association in older age groups (mean decrease between 2.29 and 2.39 PMD units). BMI did not alter the association between PMD and the number of FTPs. CONCLUSIONS: The effect of pregnancies on mammographic density does not appear to become apparent before the age of menopause. The mechanism that drives the effect of pregnancies on mammographic density appears to be counter-regulated by other influences on mammographic density in younger patients.

Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.

Gynecologic oncologists' attitudes and practices relating to integrative medicine: results of a nationwide AGO survey.

PURPOSE: The growing popularity and acceptance of integrative medicine is evident both among patients and among the oncologists treating them. As little data are available regarding health-care professionals' knowledge, attitudes, and practices relating to the topic, a nationwide online survey was designed. METHODS: Over a period of 11 weeks (from July 15 to September 30, 2014) a self-administered, 17-item online survey was sent to all 676 members of the Research Group on Gynecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie) in the German Cancer Society. The questionnaire items addressed the use of integrative therapy methods, fields of indications for them, advice services provided, level of specific qualifications, and other topics. RESULTS: Of the 104 respondents (15.4%) using integrative medicine, 93% reported that integrative therapy was offered to breast cancer patients. The second most frequent type of tumor in connection with which integrative therapy methods were recommended was ovarian cancer, at 80% of the participants using integrative medicine. Exercise, nutritional therapy, dietary supplements, herbal medicines, and acupuncture were the methods the patients were most commonly advised to use. CONCLUSION: There is considerable interest in integrative medicine among gynecological oncologists, but integrative therapy approaches are at present poorly implemented in routine clinical work. Furthermore there is a lack of specific training. Whether future efforts should focus on extending counseling services on integrative medicine approaches in gynecologic oncology or not, have to be discussed. Evidence-based training on integrative medicine should be implemented in order to safely guide patients in their wish to do something by themselves.

Mammographic density is the main correlate of tumors detected on ultrasound but not on mammography.

Although mammography screening programs do not include ultrasound examinations, some diagnostic units do provide women with both mammography and ultrasonography. This article is concerned with estimating the risk of a breast cancer patient diagnosed in a hospital-based mammography unit having a tumor that is visible on ultrasound but not on mammography. A total of 1,399 women with invasive breast cancer from a hospital-based diagnostic mammography unit were included in this retrospective study. For inclusion, mammograms from the time of the primary diagnosis had to be available for computer-assisted assessment of percentage mammographic density (PMD), as well as Breast Imaging Reporting and Data System (BIRADS) assessment of mammography. In addition, ultrasound findings were available for the complete cohort as part of routine diagnostic procedures, regardless of any patient or imaging characteristics. Logistic regression analyses were conducted to identify predictors of mammography failure, defined as BIRADS assessment 1 or 2. The probability that the visibility of a tumor might be masked at diagnosis was estimated using a regression model with the identified predictors. Tumors were only visible on ultrasound in 107 cases (7.6%). PMD was the strongest predictor for mammography failure, but age, body mass index and previous breast surgery also influenced the risk, independently of the PMD. Risk probabilities ranged from 1% for a defined low-risk group up to 40% for a high-risk group. These findings might help identify women who should be offered ultrasound examinations in addition to mammography.

Knowledge and attitudes regarding medical research studies among patients with breast cancer and gynecological diseases.

BACKGROUND: Medical research studies are becoming increasingly important for optimizing the prevention, diagnosis and treatment of illnesses. Participation in research studies can have many benefits for patients. In randomized and controlled clinical studies, they can receive the best possible medical care currently available. However, only a small proportion of patients nowadays are treated within the framework of medical research. The primary endpoint of this study was to discover what level of knowledge patients have about clinical studies and how they currently perceive them, in order to identify ways of optimizing the information provided about studies from the patients' point of view. METHODS: The study included 2546 patients (breast cancer 21.6%, gynecological cancer 8.3%, obstetrics 32.7%, endometriosis 7.8%, fertility treatment 3.2%, other benign gynecological illnesses 19.2%, no information for 7.2%) in the outpatient clinic (45.2%) and in the in-patient sector (54.8%) at the Department of Gynecology at Erlangen University Hospital and associated centers. In the single-center study, conducted between January 2011 and January 2012, the patients were asked about their level of knowledge regarding the background to medical research studies and the ways in which they are carried out and used. The patients were also asked how they perceived medical studies and how they thought study conditions might be optimized. The three-page questionnaire was included in the feedback sheet received by patients as part of the hospital's quality management system. RESULTS: As a whole, the group only had moderate knowledge about clinical studies. A majority of the respondents considered that studies were valuable (91.6%), but only a few were also willing to take part in them (58.4%). Knowledge and willingness to participate strongly depended on age (P < 0.001), educational level (P < 0.001) and patient group (P < 0.001). Most patients would prefer to decide about participating in studies through a discussion with their outpatient physicians. CONCLUSIONS: The information that patients have about clinical studies affects whether they participate in them. It is therefore extremely important for patients to be well informed, for their anxieties about participation to be relieved, and for the benefits of participation to be explained to them.

FemZone trial: a randomized phase II trial comparing neoadjuvant letrozole and zoledronic acid with letrozole in primary breast cancer patients.

BACKGROUND: The objective of this prospectively randomized phase II trial (Trial registration: EUCTR2004-004007-37-DE) was to compare the clinical response of primary breast cancer patients to neoadjuvant therapy with letrozole alone (LET) or letrozole and zoledronic acid (LET + ZOL). METHODS: Patients were randomly assigned to receive either LET 2.5 mg/day (n = 79) or the combination of LET 2.5 mg/day and a total of seven infusions of ZOL 4 mg every 4 weeks (n = 89) for 6 months. Primary endpoint was clinical response rate as assessed by mammogram readings. The study was terminated prematurely due to insufficient recruitment. We report here on an exploratory analysis of this data. RESULTS: Central assessment of tumor sizes during the treatment period was available for 131 patients (66 LET, 65 LET + ZOL). Clinical responses (complete or partial) were seen in 54.5% (95% CI: 41.8-66.9) of the patients in the LET arm and 69.2% (95% CI: 56.6-80.1) of those in the LET + ZOL arm (P = 0.106). A multivariate model showed an OR of 1.72 (95% CI: 0.83-3.59) for the experimental arm. CONCLUSION: No increase in the clinical response rate was observed with the addition of ZOL to a neoadjuvant treatment regimen with LET. However a trend towards a better reponse in the LET + ZOL arm could be observed. This trend is consistent with previous studies that have investigated the addition of ZOL to chemotherapy, and it may support the evidence for a direct antitumor action of zoledronic acid.

Low-dose methotrexate treatment in ectopic pregnancy: a retrospective analysis of 164 ectopic pregnancies treated between 2000 and 2008.

PURPOSE: Ectopic pregnancy is an acute, potentially life-threatening condition. The aim of this study was to compare the results of surgery and methotrexate treatment in women with ectopic pregnancy, along with a review of the literature. METHODS: 164 women with ectopic pregnancy, treated from 2000 to 2008 at the university gynecology department, were examined in a retrospective analysis. Patients with diagnosed ectopic pregnancy underwent one of the following treatments: Salpingotomy, salpingectomy or administration of a single dose of 30 mg methotrexate. The main outcome measures were treatment success rate, rate of patients wishing to have children after the ectopic pregnancy, and rates of pregnancy, live births, recurrent ectopic pregnancy, miscarriage, use of assisted reproduction and side effects. RESULTS: There were no significant differences in success rates between the groups (methotrexate 83.9 %, salpingotomy 88.2 %, salpingectomy 96.8 %). Significantly more patients in the salpingotomy group wished to become pregnant afterward than in the salpingectomy group. No significant differences were observed between the groups in the rates of intrauterine pregnancy, live births, recurrences, miscarriages, or side effects. CONCLUSIONS: With defined inclusion criteria, similar results can be achieved with low-dose single administration of 30 mg methotrexate in comparison with surgical treatment for ectopic pregnancy. On the basis of the data presented here, further research to establish optimal dosages for methotrexate is needed.

Comprehensive visualization of paresthesia in breast cancer survivors.

PURPOSE: As breast cancer survivors are benefiting increasingly from advanced forms of therapy, the side effects of locoregional treatment in the adjuvant setting are becoming more and more important. This article presents a new method of assessing the spatial distribution of paresthesia in breast cancer survivors after different locoregional treatments. METHODS: A structured questionnaire assessing paresthesia, with body pictograms for marking paresthesia areas, was completed by 343 breast cancer survivors. The image information was digitized, generating gray-scale summation images with numbers from 0, indicating black (100 % of the patients had paresthesia), to 255, indicating white (none had paresthesia). The resulting map visualization showed the locations of paresthesia on body pictograms. The group included patients who had undergone breast-conserving surgery (BCS) and mastectomy, and also patients who had received percutaneous and interstitial radiation. RESULTS: A total of 56.5 % of the patients stated that they had paresthesia. The paresthesia areas were distributed within the range suggested by clinical experience. Most patients stated that they had paresthesia in the upper outer quadrant and axilla. Patients who had undergone mastectomy or percutaneous radiotherapy appeared to have more paresthesia on some areas of the body surface. Patients who had undergone mastectomy indicated larger areas of paresthesia than those with BCS-4,066 pixels (px) vs. 2,275 px. Radiotherapy did not appear to influence the spatial distribution of paresthesia. CONCLUSIONS: Paresthesia is a common symptom after breast cancer treatment. This paper describes a new method of assessing this side effect to improve and individualize treatment for it in the future.

Prognostic relevance of Ki-67 in the primary tumor for survival after a diagnosis of distant metastasis.

Prediction of the prognosis for metastatic breast cancer patients depends on molecular subtypes similar to those found in patients with primary breast cancer. Several studies have shown that estrogen receptor (ER) and progesterone receptor (PR) status determine the course of the disease and the prognosis. As Ki-67 helps to differentiate molecular subtypes in patients with primary breast cancer, the aim of this study was to assess the prognostic relevance of Ki-67 in the primary tumor in relation to its prognostic relevance for patients with metastatic breast cancer. A total of 467 patients with invasive breast cancer were identified in the database of a single breast cancer center, in whom Ki-67 had been assessed in tumor material from the breast at the time of the primary diagnosis and who had developed a metastasis at any time during the subsequent course. For these patients, tumor and patient characteristics were used to determine prognostic factors relative to overall survival after the diagnosis of distant metastases. Ki-67 was added to this model to investigate whether this might improve the prediction of overall survival. In the multivariate Cox model, age at diagnosis, body mass index, nodal status, tumor size, ER and PR status, and time from diagnosis to metastasis were identified as relevant prognostic factors. Adding Ki-67 to the model improved the prediction of overall survival. There was also a significant and relevant interaction with the PR status. In patients with a low-proliferation primary tumor, a high level of PR expression would indicate an extraordinarily good prognosis (HR 0.39; 95 % CI, 0.23-0.66). In patients with higher-proliferation primary tumors, PR status was not capable of differentiating prognostic groups. Ki-67 is useful in addition to known prognostic factors for breast cancer. It is able to indicate a group of women with a poorer prognosis, specifically in the group of patients with PR-positive breast cancer.

Financing of certified centers: a willingness-to-pay analysis.

INTRODUCTION: Although care in certified breast centers is now established throughout Germany, numerous services are still not being reimbursed. This also affects other centers involved in the specialty of gynecology such as gynecological cancer centers, perinatal centers, and endometriosis centers. Although a certified center is entitled to charge additional fees, these are in most cases not reimbursed. Calculation of additional costs is limited by the fact that data from the Institute for the Hospital Reimbursement System (Institut für das Entgeltsystem im Krankenhaus, InEK) do not reflect interdisciplinary services and procedures. For decision-makers, society's willingness to pay is an important factor in guiding decisions on the basis of social priorities. A hypothetical maximum willingness to pay can be calculated using a willingness-to-pay analysis, making it possible to identify deficiencies in the arbitrary setting of health budgets at the macro-level. MATERIALS AND METHODS: In a multicenter study conducted between November 2009 and December 2010, 2,469 patients at a university hospital and at a non-university hospital were asked about the extent of their awareness of certified centers, the influence of centers on hospital presentation, and about personal attitudes toward quality-oriented reimbursement. A subjective assessment of possible additional charges was calculated using a willingness-to-pay analysis. RESULTS: In the overall group, 53.4 % of the patients were aware of what a certified center is and 27.4 % had specific information (obstetrics 40.0/32.3 %; mastology 66.8/23.2 %; gynecological oncology 54.7/27.3 %; P < 0.001). For 43.8 %, a certified center was one reason or the major reason for presentation (obstetrics 26.2 %; mastology 66.8 %; gynecological oncology 46.6 %; P < 0.001). A total of 72.6 % were in favor of quality-oriented reimbursement and 69.7 % were in favor of an additional charge for a certified center amounting to €538.56 (mastology €643.65, obstetrics €474.67, gynecological oncology €532.47). In all, 33.9 % would accept an increase in health-insurance fees (averaging 0.3865 %), and 28.3 % were in favor of reduced remuneration for non-certified centers. CONCLUSIONS: The existence of certified centers is being increasingly recognized by patients. Additional charges for certified centers are generally supported. There is therefore a clear demand for them-from patients as well. This may be useful when negotiations are being conducted.

Characterizing mammographic images by using generic texture features.

INTRODUCTION: Although mammographic density is an established risk factor for breast cancer, its use is limited in clinical practice because of a lack of automated and standardized measurement methods. The aims of this study were to evaluate a variety of automated texture features in mammograms as risk factors for breast cancer and to compare them with the percentage mammographic density (PMD) by using a case-control study design. METHODS: A case-control study including 864 cases and 418 controls was analyzed automatically. Four hundred seventy features were explored as possible risk factors for breast cancer. These included statistical features, moment-based features, spectral-energy features, and form-based features. An elaborate variable selection process using logistic regression analyses was performed to identify those features that were associated with case-control status. In addition, PMD was assessed and included in the regression model. RESULTS: Of the 470 image-analysis features explored, 46 remained in the final logistic regression model. An area under the curve of 0.79, with an odds ratio per standard deviation change of 2.88 (95% CI, 2.28 to 3.65), was obtained with validation data. Adding the PMD did not improve the final model. CONCLUSIONS: Using texture features to predict the risk of breast cancer appears feasible. PMD did not show any additional value in this study. With regard to the features assessed, most of the analysis tools appeared to reflect mammographic density, although some features did not correlate with PMD. It remains to be investigated in larger case-control studies whether these features can contribute to increased prediction accuracy.

Association of mammographic density with hormone receptors in invasive breast cancers: results from a case-only study.

For many breast cancer (BC) risk factors, there is growing evidence concerning molecular subtypes for which the risk factor is specific. With regard to mammographic density (MD), there are inconsistent data concerning its association with estrogen receptor (ER) and progesterone receptor (PR) expression. The aim of our study was to analyze the association between ER and PR expression and MD. In our case-only study, data on BC risk factors, hormone receptor expression and MD were available for 2,410 patients with incident BC. MD was assessed as percent MD (PMD) using a semiautomated method by two readers for every patient. The association of ER/PR and PMD was studied with multifactorial analyses of covariance with PMD as the target variable and including well-known factors that are also associated with MD, such as age, parity, use of hormone replacement therapy, and body mass index (BMI). In addition to the commonly known associations between PMD and age, parity, BMI and hormone replacement therapy, a significant inverse association was found between PMD and ER expression levels. Patients with ER-negative tumors had an average PMD of 38%, whereas patients with high ER expression had a PMD of 35%. A statistical trend toward a positive association between PMD and PR expression was also seen. PMD appears to be inversely associated with ER expression and may correlate positively with PR expression. These effects were independent of other risk factors such as age, BMI, parity, and hormone replacement therapy, possibly suggesting other pathways that mediate this effect.