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.