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@article{faucris.208410575,
abstract = {BACKGROUND: Breast cancer is the most common cancer in women. 12-15% of all tumors are triple-negative breast cancers (TNBC). So far, TNBC has been mainly associated with mutations in BRCA1. The presence of other predisposing genes seems likely since DNA damage repair is a complex process that involves several genes. Therefore we investigated if mutations in other genes are involved in cancer development and whether TNBC is an additional indicator of mutational status besides family history and age of onset.
METHODS: We performed a germline panel-based screening of 10 high and low-moderate penetrance breast cancer susceptibility genes (BRCA1, BRCA2, ATM, CDH1, CHEK2, NBN, PALB2, RAD51C, RAD51D and TP53) in 229 consecutive individuals affected with TNBC unselected for age, family history or bilateral disease. Within this cohort we compared the number of mutation carriers fulfilling clinical selection criteria with the total number of carriers identified.
RESULTS: Age at diagnosis ranged from 23 to 80 years with an average age of 50.2 years. In 57 women (24.9%) we detected a pathogenic mutation, with a higher frequency (29.7%) in the group manifesting cancer before 60 years. Deleterious BRCA1 mutations occurred in 14.8% of TNBC patients. These were predominantly recurrent frameshift mutations (24/34, 70.6%). Deleterious BRCA2 mutations occurred in 5.7% of patients, all but one (c.1813dupA) being unique. While no mutations were found in CDH1 and TP53, 10 mutations were detected in one of the six other predisposition genes. Remarkably, neither of the ATM, RAD51D, CHEK2 and PALB2 mutation carriers had a family history. Furthermore, patients with non-BRCA1/2 mutations were not significantly younger than mutation negative women (p = 0.3341). Most importantly, among the 57 mutation carriers, ten (17.5%) would be missed using current clinical testing criteria including five (8%) with BRCA1/2 mutations.
CONCLUSIONS: In summary, our data confirm and expand previous studies of a high frequency of germline mutations in genes associated with ineffective repair of DNA damage in women with TNBCs. Neither age of onset, contralateral disease nor family history were able to discern all mutation positive individuals. Therefore, TNBC should be considered as an additional criterion for panel based genetic testing.},
author = {Hoyer, Juliane and Vasileiou, Georgia and Uebe, Steffen and Wunderle, Marius and Kraus, Cornelia and Fasching, Peter and Thiel, Christian and Hartmann, Arndt and Beckmann, Matthias and Lux, Michael P. and Reis, André},
doi = {10.1186/s12885-018-4821-8},
faupublication = {yes},
journal = {BMC Cancer},
note = {EVALuna2:34811},
peerreviewed = {Yes},
title = {{Addition} of triple negativity of breast cancer as an indicator for germline mutations in predisposing genes increases sensitivity of clinical selection criteria},
volume = {18},
year = {2018}
}
@article{faucris.237821281,
abstract = {Purpose: Second opinions in oncology are becoming increasingly important in an era of more complex treatments and a growing demand for information by patients. Therefore, we analyzed their effects and influencing factors like patients’ motives, subjective extent of information and satisfaction with communications. Methods: This prospective study evaluated second opinions for patients with breast cancer or gynecological malignancy. The patients received a questionnaire before and two months after, which inquired expectations, reasons, and satisfaction with the second opinion and the attending physicians. Results: A total of 164 patients were included and the majority had breast cancer (75.0%). Receiving the second opinion made 89.7% feel better informed, their need for information decreased (from 75.3% to 39.2%, P < 0.0001), and satisfaction with doctor–patient communications increased (from 61.9 to 91.8%, P = 0.0002). There were various reasons for requesting a second opinion, e.g., the extremely stressful situation of a cancer diagnosis, hope for change in the treatment recommendation or dissatisfaction with the initial physicians. Conclusions: Second opinions can lead to significantly greater patient satisfaction, meeting the need for information and leading to better management of patients in the extremely stressful situation of a cancer diagnosis. Doctor–patient communications play a key role.},
author = {Löhberg, Christian and Meyer, Julia and Häberle, Lothar and Hack, Carolin and Jud, Sebastian and Hein, Alexander and Wunderle, Marius and Emons, Julius and Gaß, Paul and Fasching, Peter and Egloffstein, Sainab and Krebs, Jessica and Erim, Yesim and Beckmann, Matthias and Lux, Michael P. and Wasner, Sonja},
doi = {10.1007/s00404-020-05525-2},
faupublication = {yes},
journal = {Archives of Gynecology and Obstetrics},
keywords = {Breast cancer; Doctor–patient communication; Gynecological malignancy; Oncology center; Patient satisfaction; Second opinion},
note = {CRIS-Team Scopus Importer:2020-04-28},
peerreviewed = {Yes},
title = {{Analysis} of motives and patient satisfaction in oncological second opinions provided by a certified university breast and gynecological cancer center},
year = {2020}
}
@article{faucris.242202004,
abstract = {Introduction: Oncological second opinions are becoming increasingly important given more complex treatment strategies, simultaneously more patients use complementary and alternative medicine (CAM), and many comprehensive cancer centers initiate integrative medicine programs. The present study focuses on analyzing the effects of a second opinion in relation to attitudes toward CAM. Methods: In this prospective study patients (n = 97) with a diagnosis of breast cancer or gynecological malignancies who had requested a second opinion received a questionnaire before and after the second opinion concerning their attitudes toward CAM. Results: The majority of patients had breast cancer (72.2%, n = 70). Only 6.2% (n = 6) stated that they had been informed about CAM by the doctors who treated them first, 21.6% (n = 21) had received information about it when seeking the second opinion. After the first opinion, 42.3% (n = 41) wanted to try CAM, the same proportion trusted orthodox medicine alone. After the second opinion, 24 patients (24.7%) wanted to try CAM, while 38.1% (n = 37) relied exclusively on orthodox medicine. There was a significant correlation between an increased patients' need for information and interest in CAM (p = 0.02). Conclusions: Today, aspects of CAM still are very often no part of oncological first and second opinions. This might hence lead to discouraging patients to try out CAM and therefore integrative medicine programs in comprehensive cancer centers might be problem-solving.},
author = {Hack, Carolin and Wasner, Sonja and Meyer, Julia and Häberle, Lothar and Jud, Sebastian and Hein, Alexander and Wunderle, Marius and Emons, Julius and Gaß, Paul and Fasching, Peter and Egloffstein, Sainab and Beckmann, Matthias and Lux, Michael P. and Löhberg, Christian},
doi = {10.1159/000508235},
faupublication = {yes},
journal = {Complementary Medicine Research},
keywords = {Breast cancer; Complementary and alternative medicine; Gynecological malignancies; Integrative medicine; Oncological center; Second opinion},
note = {CRIS-Team Scopus Importer:2020-09-04},
peerreviewed = {Yes},
title = {{Analysis} of {Oncological} {Second} {Opinions} in a {Certified} {University} {Breast} and {Gynecological} {Cancer} {Center} in {Relation} to {Complementary} and {Alternative} {Medicine}},
year = {2020}
}
@article{faucris.242201262,
abstract = {Introduction: Oncological second opinions are becoming increasingly important in the era of complex treatments and established certified cancer centers. Oncological guidelines with the highest levels of evidence are available, but these can only be effective to the extent that they are implemented. Therefore, we analyzed the effects of second opinions with regard to their agreement with first opinions and conformity with guidelines. Methods: In 164 patients with a diagnosis of breast cancer or gynecological malignancy who requested a second opinion, the first and second opinions, established at the interdisciplinary tumor conference, and conformity with the guidelines were evaluated. Results: The first opinion was not in agreement with the guidelines in 34.8% (15.2% diagnosis, 12.8% surgical therapy, 13.4% systemic therapy, and 5.5% radiotherapy), and the recommendations were optimized in the second opinion in 56.7% (28.7% diagnosis, 15.9% surgical therapy, 30.5% systemic therapy, and 8.5% radiotherapy). Conclusions: Oncological second opinions showed significant effects and one-third of first opinions were not in conformity with the guidelines. In a significant proportion of cases, the existing treatment plan was changed or supplemented to allow modern and individualized treatment approaches.},
author = {Lux, Michael P. and Wasner, Sonja and Meyer, Julia and Häberle, Lothar and Hack, Carolin and Jud, Sebastian and Hein, Alexander and Wunderle, Marius and Emons, Julius and Gaß, Paul and Fasching, Peter and Egloffstein, Sainab and Krebs, Jessica and Erim, Yesim and Beckmann, Matthias and Löhberg, Christian},
doi = {10.1159/000509127},
faupublication = {yes},
journal = {Breast Care},
note = {CRIS-Team Scopus Importer:2020-09-04},
peerreviewed = {Yes},
title = {{Analysis} of {Oncological} {Second} {Opinions} in a {Certified} {University} {Breast} and {Gynecological} {Cancer} {Center} {Regarding} {Consensus} between the {First} and {Second} {Opinion} and {Conformity} with the {Guidelines}},
year = {2020}
}
@article{faucris.243041623,
abstract = {Background: Mammography can identify calcifications up to 50–100 μm in size as a surrogate parameter for breast cancer or ductal carcinoma in situ (DCIS). Microcalcifications measuring <50 µm are also associated with breast cancer or DCIS and are frequently not detected on mammography, although they can be detected with dark-field imaging. This study examined whether additional breast examination using X-ray dark-field imaging can increase the detection rate of calcifications. Advances in knowledge: (1) evaluation of additional modality of breast imaging; (2) specific evaluation of breast calcifications. Implications for patient care: the addition of X-ray dark-field imaging to conventional mammography could detect additional calcifications. Methods: Talbot–Lau X-ray phase–contrast imaging and X-ray dark-field imaging were used to acquire images of breast specimens. The radiation dosage with the technique is comparable with conventional mammography. Three X-ray gratings with periods of 5–10 µm between the X-ray tube and the flat-panel detector provide three different images in a single sequence: the conventional attenuation image, differential phase image, and dark-field image. The images were read by radiologists. Radiological findings were marked and examined pathologically. The results were described in a descriptive manner. Results: A total of 81 breast specimens were investigated with the two methods; 199 significant structures were processed pathologically, consisting of 123 benign and 76 malignant lesions (DCIS or invasive breast cancer). X-ray dark-field imaging identified 15 additional histologically confirmed carcinoma lesions that were visible but not declared suspicious on digital mammography alone. Another four malignant lesions that were not visible on mammography were exclusively detected with X-ray dark-field imaging. Conclusions: Adding X-ray dark-field imaging to digital mammography increases the detection rate for breast cancer and DCIS associated lesions with micrometer-sized calcifications. The use of X-ray dark-field imaging may be able to provide more accurate and detailed radiological classification of suspicious breast lesions. Adding X-ray dark-field imaging to mammography may be able to increase the detection rate and improve preoperative planning in deciding between mastectomy or breast-conserving therapy, particularly in patients with invasive lobular breast cancer.},
author = {Emons, Julius and Fasching, Peter and Wunderle, Marius and Heindl, Felix and Rieger, Jens and Horn, Florian and Pelzer, Georg and Ritter, André and Weber, Thomas and Radicke, Marcus and Polifka, Iris and Wachter, David and Wenkel, Evelyn and Michel, Thilo and Uder, Michael and Hartmann, Arndt and Anton, Gisela and Beckmann, Matthias and Schulz-Wendtland, Rüdiger and Jud, Sebastian},
doi = {10.1177/1758835920957932},
faupublication = {yes},
journal = {Therapeutic Advances in Medical Oncology},
keywords = {breast cancer; interferometry; mammography; microcalcifications},
note = {CRIS-Team Scopus Importer:2020-09-25},
peerreviewed = {Yes},
title = {{Assessment} of the additional clinical potential of {X}-ray dark-field imaging for breast cancer in a preclinical setup},
volume = {12},
year = {2020}
}
@article{faucris.214903150,
abstract = {PurposeEvidence 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.MethodsThe 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.ResultsIn 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).ConclusionsThis 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.},
author = {Wunderle, Marius and Pretscher, Jutta and Brucker, Sara Y. and Volz, Bernhard and Hartmann, Arndt and Fießler, Cornelia and Hein, Alexander and Häberle, Lothar and Jud, Sebastian and Lux, Michael P. and Janni, Wolfgang and Löhberg, Christian and Hartkopf, Andreas D. and Walter, Christina B. and Baake, Gerold and Fridman, Alexander and Malter, Wolfram and Wuerstlein, Rachel and Harbeck, Nadia and Hoffmann, Oliver and Kuemmel, Sherko and Martin, Bernhard and Thomssen, Christoph and Graf, Heiko and Wolf, Christopher and Bayer, Christian M. and Hack, Carolin and Almstedt, Katrin and Gaß, Paul and Heindl, Felix and Brodkorb, Tobias F. and Nabieva, Naiba and Lindner, Christoph and Kolberg, Hans-Christian and Krabisch, Petra and Weigel, Michael and Steinfeld-Birg, Dieter and Kohls, Andreas and Brucker, Cosima and Schulz, Volker and Fischer, Gunnar and Pelzer, Volker and Wallwiener, Diethelm and Rack, Brigitte and Fehm, Tanja and Rody, Achim and Maass, Nicolai and Beckmann, Matthias and Fasching, Peter and Rauh, Claudia},
doi = {10.1007/s10549-018-05115-6},
faupublication = {yes},
journal = {Breast Cancer Research and Treatment},
note = {CRIS-Team WoS Importer:2019-03-29},
pages = {453-461},
peerreviewed = {Yes},
title = {{Association} between breast cancer risk factors and molecular type in postmenopausal patients with hormone receptor-positive early breast cancer},
volume = {174},
year = {2019}
}
@article{faucris.111708784,
abstract = {The combination of different imaging modalities through the use of fusion devices promises significant diagnostic improvement for breast pathology. The aim of this study was to evaluate image quality and clinical feasibility of a prototype fusion device (fusion prototype) constructed from a standard tomosynthesis mammography unit and a standard 3D ultrasound probe using a new method of breast compression.Imaging was performed on 5 mastectomy specimens from patients with confirmed DCIS or invasive carcinoma (BI-RADS ((TM)) 6). For the preclinical fusion prototype an ABVS system ultrasound probe from an Acuson S2000 was integrated into a MAMMOMAT Inspiration (both Siemens Healthcare Ltd) and, with the aid of a newly developed compression plate, digital mammogram and automated 3D ultrasound images were obtained.The quality of digital mammogram images produced by the fusion prototype was comparable to those produced using conventional compression. The newly developed compression plate did not influence the applied x-ray dose. The method was not more labour intensive or time-consuming than conventional mammography. From the technical perspective, fusion of the two modalities was achievable.In this study, using only a few mastectomy specimens, the fusion of an automated 3D ultrasound machine with a standard mammography unit delivered images of comparable quality to conventional mammography. The device allows simultaneous ultrasound - the second important imaging modality in complementary breast diagnostics - without increasing examination time or requiring additional staff.},
author = {Schulz-Wendtland, Rüdiger and Jud, Sebastian and Fasching, Peter and Hartmann, Arndt and Radicke, Marcus and Rauh, Claudia and Uder, Michael and Wunderle, Marius and Gaß, Paul and Langemann, Hanna and Beckmann, Matthias and Emons, Julius},
doi = {10.1055/s-0043-107034},
faupublication = {yes},
journal = {Geburtshilfe und Frauenheilkunde},
note = {EVALuna2:6849},
pages = {679-685},
peerreviewed = {Yes},
title = {{A} {Standard} {Mammography} {Unit} - {Standard} {3D} {Ultrasound} {Probe} {Fusion} {Prototype}: {First} {Results}},
volume = {77},
year = {2017}
}
@article{faucris.227596119,
abstract = {Early breast cancer detection programs depend for effectiveness on the participation rate, which is affected by risk factor awareness. This study investigated changes in women's risk factor awareness between 2004 and 2016. Results from a 2004 survey of 2107 healthy women were compared with new data obtained using the same questionnaire in 2016, with 866 participants indicating their knowledge and perceptions regarding breast cancer incidence, risk factors, risk perceptions, and levels of concern. Logistic regression models assessed the influence of time point (2004 vs. 2016) on correct recognition of risk factors such as age at first childbirth, childlessness, lack of breastfeeding, hormone replacement therapy (HRT), and family history. Regression models were adjusted for common sociodemographic characteristics. Reproductive risk factors were regarded as influencing breast cancer risk less often. In 2004, age at first birth, childlessness, and lack of breastfeeding were regarded as risk factors by 24, 32, and 37%, respectively, in comparison with only 15, 18, and 23% in 2016. All changes were statistically significant. Awareness of HRT as a risk factor increased significantly (36-57%), and family history was recognized as a risk by 75 and 73% in 2004 and 2016, respectively. Most women recognized family history as a breast cancer risk factor. This did not change, reflecting the topic's media prominence. Awareness of HRT as a risk factor increased, probably owing to public information after the large HRT studies. It is unclear why reproductive risk factors are less frequently recognized; educational programs should address this information deficit.},
author = {Poehls, Uwe G. and Hack, Carolin and Wunderle, Marius and Renner, Stefan P. and Lux, Michael P. and Beckmann, Matthias and Fasching, Peter and Nabieva, Naiba},
doi = {10.1097/CEJ.0000000000000500},
faupublication = {yes},
journal = {European Journal of Cancer Prevention},
note = {CRIS-Team Scopus Importer:2019-10-08},
pages = {515-521},
peerreviewed = {Yes},
title = {{Awareness} of breast cancer incidence and risk factors among healthy women in {Germany}: an update after 10 years},
volume = {28},
year = {2019}
}
@article{faucris.205567447,
abstract = {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.},
author = {Wunderle, Marius and Gaß, Paul and Häberle, Lothar and Flesch, Vivien M. and Rauh, Claudia and Bani, Mayada and Hack, Carolin and Schrauder, Michael G. and Jud, Sebastian and Emons, Julius and Erber, Ramona and Ekici, Arif Bülent and Hoyer, Juliane and Vasileiou, Georgia and Kraus, Cornelia and Reis, André and Hartmann, Arndt and Lux, Michael P. and Beckmann, Matthias and Fasching, Peter and Hein, Alexander},
doi = {10.1007/s10549-018-4797-8},
faupublication = {yes},
journal = {Breast Cancer Research and Treatment},
note = {EVALuna2:34606},
pages = {85-94},
peerreviewed = {Yes},
title = {{BRCA} mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients},
volume = {171},
year = {2018}
}
@article{faucris.241258806,
abstract = {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.},
author = {Vasileiou, Georgia and Costa, Maria J. and Long, Christopher and Wetzler, Iris and Hoyer, Juliane and Kraus, Cornelia and Popp, Bernt and Emons, Julius and Wunderle, Marius and Wenkel, Evelyn and Uder, Michael and Beckmann, Matthias and Jud, Sebastian and Fasching, Peter and Reis, André and Hammon, Matthias and Cavallaro, Alexander Josef},
doi = {10.1186/s12880-020-00483-2},
faupublication = {yes},
journal = {BMC Medical Imaging},
keywords = {BRCA1/2; Breast cancer; HBOC; L-PCR; MRI; Texture analysis},
note = {CRIS-Team Scopus Importer:2020-08-07},
pages = {86-},
peerreviewed = {unknown},
title = {{Breast} {MRI} texture analysis for prediction of {BRCA}-associated genetic risk},
volume = {20},
year = {2020}
}
@inproceedings{faucris.284515520,
address = {STUTTGART},
author = {Behrens, Annika and Wunderle, Marius and Häberle, Lothar and Stamminger, Marc and Zint, Daniel and Emons, Julius and Heindl, Felix and Hack, Caroline and Ohlmeyer, Sabine and Uder, Michael and Beckmann, Matthias and Fasching, Peter},
booktitle = {GEBURTSHILFE UND FRAUENHEILKUNDE},
doi = {10.1055/s-0042-1756758},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2022-11-04},
pages = {E49-E50},
peerreviewed = {unknown},
publisher = {GEORG THIEME VERLAG KG},
title = {{Breast} volume assessment with a smart phone device compared to {MRI}},
year = {2022}
}
@article{faucris.226997490,
abstract = {BACKGROUND: Growing demand for risk-reducing surgery in individuals with inherited susceptibility to cancer leads to the question whether these procedures are cost effective for the executing hospitals. This study compared the clinical costs for bilateral risk-reducing mastectomy (BRRM) with and without different types of reconstruction, risk-reducing salpingo-oophorectomy (RRSO), and their combinations with corresponding reimbursements in the statutory health-care system in Germany. PATIENTS AND METHODS: Real total costs of care for BRRM with and without reconstruction, RRSO, and their combinations were calculated as the sum of all personnel and technical costs. These costs calculated in a German University hospital were compared with the sum of all reimbursements in the German DRG-based health-care system. RESULTS: While sole RRSO, BRRM without reconstruction, and BRRM with secondary DIEP (deep inferior epigastric perforator)-reconstruction still result in a small benefit, we even found shortfalls for the hospital with all other prophylactic operations under consideration. The calculated deficits were especially high for BRRM with implant-based breast reconstruction and for combined operations when the risk reduction is achieved with a minimum of separate operations. CONCLUSIONS: Risk-reducing surgery in BRCA-mutation carriers is frequently not cost-covering for the executing hospitals in the German health-care system. Thus, appropriate concepts are required to ensure a nationwide care.},
author = {Schrauder, Michael G. and Brunel-Geuder, Lisa and Häberle, Lothar and Wunderle, Marius and Hoyer, Juliane and Csorba, Roland and Reis, André and Schulz-Wendtland, Rüdiger and Beckmann, Matthias and Lux, Michael P.},
doi = {10.1186/s40001-019-0391-8},
faupublication = {yes},
journal = {European Journal of Medical Research},
keywords = {BRCA; Breast cancer; Cost effectiveness; Genetic counseling; Ovarian cancer},
note = {CRIS-Team Scopus Importer:2019-09-24},
pages = {32-},
peerreviewed = {unknown},
title = {{Cost} effectiveness of bilateral risk-reducing mastectomy and salpingo-oophorectomy},
volume = {24},
year = {2019}
}
@article{faucris.122612424,
abstract = {Risk-reducing surgeries are a feasible option for mitigating the risk in individuals with inherited susceptibility to cancer, but are the procedures cost-effective in the current health-care system in Germany? This study compared the health-care costs for bilateral risk-reducing mastectomy (BRRM) and risk-reducing (bilateral) salpingo-oophorectomy (RRSO) with cancer treatment costs that could potentially be prevented.The analysis is based on interdisciplinary consultations with individuals with a high familial risk for breast and ovarian cancer at the University Breast Center for Franconia (Germany) between 2009 and 2013 (370 consultations; 44 patients with BRCA1 mutations and 26 with BRCA2 mutations). Health-care costs for risk-reducing surgeries in BRCA mutation carriers were calculated as reimbursements in the German diagnosis-related groups (DRG) hospital pricing system. These costs for the health-care system were compared with the potential cancer treatment costs that could possibly be prevented by risk-reducing surgeries.Long-term health-care costs can be reduced by risk-reducing surgeries after genetic testing in BRCA mutation carriers. The health-care system in Germany would have saved EUR 136,295 if BRRM had been performed and EUR 791,653 if RRSO had been performed before the development of cancer in only 50% of the 70 mutation carriers seen in our center. Moreover, in patients with combined RRSO and BRRM (without breast reconstruction), one further life-year for a 40-year-old BRCA mutation carrier would cost EUR 2,183.Intensive care, including risk-reducing surgeries in BRCA mutation carriers, is cost-effective from the point of view of the health-care system in Germany.},
author = {Schrauder, Michael G. and Brunel-Geuder, Lisa and Häberle, Lothar and Wunderle, Marius and Hoyer, Juliane and Wiesmann da Silva Reis, André and Schulz-Wendtland, Rüdiger and Beckmann, Matthias and Lux, Michael P.},
doi = {10.1016/j.breast.2017.02.008},
faupublication = {yes},
journal = {BREAST },
note = {EVALuna2:9369},
pages = {186-191},
peerreviewed = {Yes},
title = {{Cost}-effectiveness of risk-reducing surgeries in preventing hereditary breast and ovarian cancer},
volume = {32},
year = {2017}
}
@article{faucris.214172382,
abstract = {Background: The usefulness of clinical breast examination (CBE) in general and in breast cancer screening programs has been a matter of debate. This study investigated whether adding vision-impaired medical tactile examiners (MTEs) improves the predictiveness of CBE for suspicious lesions and analyzed the feasibility and acceptability of this approach. Methods: The prospective study included 104 patients. Physicians and MTEs performed CBEs, and mammography and ultrasound results were used as the gold standard. Sensitivity and specificity were calculated and logistic regression models were used to compare the predictive value of CBE by physicians alone, MTEs alone, and physicians and MTEs combined. Results: For CBEs by physicians alone, MTEs alone, and both combined, sensitivity was 71, 82, and 89% and specificity was 55, 45, and 35%, respectively. Using adjusted logistic regression models, the validated areas under the curve were 0.685, 0.692, and 0.710 (median bootstrapped p value (DeLong) = 0.381). Conclusion: The predictive value for a suspicious breast lesion in CBEs performed by MTEs in patients without prior surgery was similar to that of physician-conducted CBEs. Including MTEs in the CBE procedure in breast units thus appears feasible and could be a way of utilizing their skills. (c) 2019 S. Karger AG, Basel},
author = {Lux, Michael P. and Emons, Julius and Bani, Mayada and Wunderle, Marius and Sell, Charlotte and Preuss, Caroline and Rauh, Claudia and Jud, Sebastian and Heindl, Felix and Langemann, Hanna and Geyer, Thomas and Brandl, Anna-Lisa and Hack, Carolin and Adler, Werner and Schulz-Wendtland, Rüdiger and Beckmann, Matthias and Fasching, Peter and Gaß, Paul},
doi = {10.1159/000495883},
faupublication = {yes},
journal = {Breast Care},
month = {Jan},
note = {CRIS-Team WoS Importer:2019-03-22},
pages = {41-47},
peerreviewed = {Yes},
title = {{Diagnostic} {Accuracy} of {Breast} {Medical} {Tactile} {Examiners} ({MTEs}): {A} {Prospective} {Pilot} {Study}},
volume = {14},
year = {2019}
}
@article{faucris.235420263,
abstract = {Background X-ray dark-field radiography could enhance mammography by providing more information on imaged tissue and microcalcifications. The dark field signal is a measure of small angle scattering and can thus provide additional information on the imaged materials. This information can be useful for material distinction of calcifications and the diagnosis of breast cancer by classifying benign and malign association of these calcifications.},
author = {Rauch, Thomas and Rieger, Jens and Pelzer, Georg and Horn, Florian and Erber, Ramona and Wunderle, Marius and Emons, Julius and Nabieva, Naiba and Fuhrich, Nicole and Michel, Thilo and Hartmann, Arndt and Fasching, Peter and Anton, Gisela},
doi = {10.1002/mp.14043},
faupublication = {yes},
journal = {Medical Physics},
note = {CRIS-Team WoS Importer:2020-03-06},
peerreviewed = {Yes},
title = {{Discrimination} analysis of breast calcifications using x-ray dark-field radiography},
year = {2020}
}
@article{faucris.231888150,
author = {Banys-Paluchowski, Malgorzata and Wunderle, Marius and Fehm, Tanja N. and Arnold, Norbert and Fasching, Peter},
faupublication = {yes},
journal = {Geburtshilfe und Frauenheilkunde},
note = {CRIS-Team WoS Importer:2020-01-17},
pages = {1249-+},
peerreviewed = {unknown},
title = {{Event} {Report} 11th {Scientific} {Symposium} of the {AGO} {TraFo}},
volume = {79},
year = {2019}
}
@article{faucris.310124452,
abstract = {Background: Individual radiosensitivity is an important factor in the occurrence of undesirable consequences of radiotherapy. The potential for increased radiosensitivity has been linked to highly penetrant heterozygous mutations in DNA repair genes such as BRCA1 and BRCA2. By studying the chromosomal radiosensitivity of BRCA1/2 mutation carriers compared to the general population, we study whether increased chromosomal radiation sensitivity is observed in patients with BRCA1/2 variants. Methods: Three-color-fluorescence in situ hybridization was performed on ex vivo-irradiated peripheral blood lymphocytes from 64 female patients with a heterozygous germline BRCA1 or BRCA2 mutation. Aberrations in chromosomes #1, #2 and #4 were analyzed. Mean breaks per metaphase (B/M) served as the parameter for chromosomal radiosensitivity. The results were compared with chromosomal radiosensitivity in a cohort of generally healthy individuals and patients with rectal cancer or breast cancer. Results: Patients with BRCA1/2 mutations (n = 64; B/M 0.47) overall showed a significantly higher chromosomal radiosensitivity than general healthy individuals (n = 211; B/M 0.41) and patients with rectal cancer (n = 379; B/M 0.44) and breast cancer (n = 147; B/M 0.45) without proven germline mutations. Chromosomal radiosensitivity varied depending on the locus of the BRCA1/2 mutation. Conclusions: BRCA1/2 mutations result in slightly increased chromosomal sensitivity to radiation. A few individual patients have a marked increase in radiation sensitivity. Therefore, these patients are at a higher risk for adverse therapeutic consequences.},
author = {Zuhair Kassem, Tara and Wunderle, Marius and Kuhlmann, Lukas and Rübner, Matthias and Hübner, Hanna and Hoyer, Juliane and Reis, André and Fasching, Peter and Beckmann, Matthias and Hack, Carolin and Fietkau, Rainer and Distel, Luitpold},
doi = {10.3390/cimb45080418},
faupublication = {yes},
journal = {Current Issues in Molecular Biology},
keywords = {BRCA1; BRCA2; breast cancer; chromosomal radiosensitivity; FISH assay; radiation oncology; radiation sensitivity testing; radiotherapy},
note = {CRIS-Team Scopus Importer:2023-09-08},
pages = {6618-6633},
peerreviewed = {Yes},
title = {{Ex} {Vivo} {Chromosomal} {Radiosensitivity} {Testing} in {Patients} with {Pathological} {Germline} {Variants} in {Breast} {Cancer} {High}-{Susceptibility} {Genes} {BReast} {CAncer} 1 and {BReast} {CAncer} 2},
volume = {45},
year = {2023}
}
@article{faucris.212414704,
abstract = {Breast and ovarian cancer (BC/OC) predisposition has been attributed to a number of high- and moderate to low-penetrance susceptibility genes. With the advent of next generation sequencing (NGS) simultaneous testing of these genes has become feasible. In this monocentric study, we report results of panel-based screening of 14 BC/OC susceptibility genes (BRCA1, BRCA2, RAD51C, RAD51D, CHEK2, PALB2, ATM, NBN, CDH1, TP53, MLH1, MSH2, MSH6 and PMS2) in a group of 581 consecutive individuals from a German population with BC and/or OC fulfilling diagnostic criteria for BRCA1 and BRCA2 testing including 179 with a triple-negative tumor. Altogether we identified 106 deleterious mutations in 105 (18%) patients in 10 different genes, including seven different exon deletions. Of these 106 mutations, 16 (15%) were novel and only six were found in BRCA1/2. To further characterize mutations located in or nearby splicing consensus sites we performed RT-PCR analysis which allowed confirmation of pathogenicity in 7 of 9 mutations analyzed. In PALB2, we identified a deleterious variant in six cases. All but one were associated with early onset BC and a positive family history indicating that penetrance for PALB2 mutations is comparable to BRCA2. Overall, extended testing beyond BRCA1/2 identified a deleterious mutation in further 6% of patients. As a downside, 89 variants of uncertain significance were identified highlighting the need for comprehensive variant databases. In conclusion, panel testing yields more accurate information on genetic cancer risk than assessing BRCA1/2 alone and wide-spread testing will help improve penetrance assessment of variants in these risk genes.},
author = {Kraus, Cornelia and Hoyer, Juliane and Vasileiou, Georgia and Wunderle, Marius and Lux, Michael P. and Fasching, Peter and Krumbiegel, Mandy and Uebe, Steffen and Reuter, Miriam and Beckmann, Matthias and Reis, André},
doi = {10.1002/ijc.30428},
faupublication = {yes},
journal = {International Journal of Cancer},
note = {EVALuna2:9340},
pages = {95-102},
peerreviewed = {Yes},
title = {{Gene} panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than {BRCA1}/2},
volume = {140},
year = {2017}
}
@article{faucris.243301628,
abstract = {The immunosuppressive human leukocyte antigens HLA-G and HLA-F are expressed on trophoblast and malignant cells. Four membrane-bound and three soluble HLA-G protein isoforms have been described, which have different immunosuppressive potentials. HLA-F has three transcript variants, resulting in three different protein isoforms. The aim of this study was to evaluate the prognostic and predictive value of HLA-G and HLA-F protein isoform expression patterns in patients with breast cancer. Core biopsies were taken at diagnosis in patients with HER2+ (n = 28), luminal B-like (n = 49) and triple-negative (n = 38) breast cancers who received neoadjuvant chemotherapy. Expression levels of HLA-F and -G were correlated with the pathological complete response (pCR). Protein expression was determined by Western blot analysis, using two antibodies for each HLA, specific for different isoforms. The protein expression of HLA isoforms did not significantly differ between breast cancer subtypes. However, some initial indications were found for an association between the soluble HLA-G6 protein isoform and pCR in HER2+ breast cancer. The study provides preliminary evidence for the evaluation of HLA-G isoform expression, in particular HLA-G6, as a possible new marker for pCR in HER2+ breast cancer.},
author = {Würfel, Franziska and Hübner, Hanna and Häberle, Lothar and Gaß, Paul and Hein, Alexander and Jud, Sebastian and Hack, Carolin and Wunderle, Marius and Schulz-Wendtland, Rüdiger and Erber, Ramona and Hartmann, Arndt and Ekici, Arif Bülent and Beckmann, Matthias and Fasching, Peter and Rübner, Matthias},
doi = {10.1038/s41598-020-72837-3},
faupublication = {yes},
journal = {Scientific Reports},
note = {CRIS-Team Scopus Importer:2020-10-02},
peerreviewed = {Yes},
title = {{HLA}-{G} and {HLA}-{F} protein isoform expression in breast cancer patients receiving neoadjuvant treatment},
volume = {10},
year = {2020}
}
@article{faucris.240769031,
abstract = {Purpose: In breast cancer, a pathological complete response (pCR) has been described as generally resulting in a favorable prognosis. However, there are subgroups, such as patients with a mutation in BRCA1 or BRCA2,in which the effect of pCR on the prognosis is suspected to be weaker. Patients with a family history of breast and/or ovarian cancer may therefore react differently in relation to pCR and prognosis, and this is investigated in this study. Patients and Methods: Breast cancer patients were identified from a clinical breast cancer registry. The study subjects had been treated with neoadjuvant chemotherapy from 2001 to 2018 and their pathological and clinical information as well as medical family history were available. They were considered to have a positive family history if they had at least 1 first-degree relative with breast and/or ovarian cancer. Multivariate logistic regression analyses were performed to study the association between family history, pCR (ypT0; ypN0), and disease-free survival (DFS). Results: Of 1,480 patients, 228 (15.4%) had a positive family history. The pCR rates were 24.9% in all patients, and 24.4% and 27.6% in those without/with a family history, respectively. Family history was not associated with a higher pCR rate (adjusted odds ratio [OR] 1.23; 95% confidence interval [CI] 0.85-1.76; p = 0.27) or a different disease-free survival (DFS; adjusted hazard ratio [HR] 1.15; 95% CI 0.88-1.52; p = 0.30). pCR did not affect the prognosis differently in relation to family history. Conclusions: In this retrospective analysis, family history was not associated with pCR and DFS. pCR improved survival, independently of family history.},
author = {Wunderle, Marius and Häberle, Lothar and Hein, Alexander and Jud, Sebastian and Lux, Michael P. and Hack, Carolin and Emons, Julius and Heindl, Felix and Nabieva, Naiba and Löhberg, Christian and Schulz-Wendtland, Rüdiger and Hartmann, Arndt and Beckmann, Matthias and Fasching, Peter and Gaß, Paul},
doi = {10.1159/000507475},
faupublication = {yes},
journal = {Breast Care},
keywords = {Breast cancer; Family history; Neoadjuvant chemotherapy; Ovarian cancer; Pathological complete response; Prognosis},
note = {CRIS-Team Scopus Importer:2020-07-24},
peerreviewed = {Yes},
title = {{Influence} of {Family} {History} of {Breast} or {Ovarian} {Cancer} on {Pathological} {Complete} {Response} and {Long}-{Term} {Prognosis} in {Breast} {Cancer} {Patients} {Treated} with {Neoadjuvant} {Chemotherapy}},
year = {2020}
}
@inproceedings{faucris.244617493,
address = {STUTTGART},
author = {Gaß, Paul and Haberle, L. and Hein, Alexander and Jud, Sebastian and Lux, M. P. and Hack, Caroline and Emons, J. and Heindl, Felix and Nabieva, Naiba and Löhberg, Christian and Schulz-Wendtland, Rüdiger and Hartmann, Arndt and Beckmann, Matthias and Fasching, Peter and Wunderle, Marius},
booktitle = {GEBURTSHILFE UND FRAUENHEILKUNDE},
doi = {10.1055/s-0040-1717891},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2020-10-30},
pages = {E111-E112},
peerreviewed = {unknown},
publisher = {GEORG THIEME VERLAG KG},
title = {{Influence} of the {Family} {Anamnesis} of {Breast} or {Ovarian} {Cancer} on the pathological {Complete} {Remission} and the {Prognosis} in {Patients} with {Breast} {Cancer} after neoadjuvant {Chemotherapy}},
year = {2020}
}
@article{faucris.207712299,
abstract = {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.},
author = {Emons, Julius and Wunderle, Marius and Hartmann, Arndt and Radicke, Marcus and Rauh, Claudia and Uder, Michael and Gaß, Paul and Fasching, Peter and Langemann, Hanna and Beckmann, Matthias and Schulz-Wendtland, Rüdiger and Jud, Sebastian},
doi = {10.1177/0284185118762249},
faupublication = {yes},
journal = {Acta Radiologica},
note = {EVALuna2:34810},
pages = {1406-1413},
peerreviewed = {Yes},
title = {{Initial} clinical results with a fusion prototype for mammography and three-dimensional ultrasound with a standard mammography system and a standard ultrasound probe},
volume = {59},
year = {2018}
}
@article{faucris.294861978,
author = {Preuss, Caroline and Wunderle, Marius and Hack, Carolin and Beckmann, Matthias and Wenkel, Evelyn and Jud, Sebastian and Heindl, Felix},
doi = {10.1055/a-1924-3194},
faupublication = {yes},
journal = {Deutsche Medizinische Wochenschrift},
note = {CRIS-Team WoS Importer:2023-03-31},
pages = {301-305},
peerreviewed = {unknown},
title = {{Mammary} carcinoma in men},
volume = {148},
year = {2023}
}
@article{faucris.280972958,
abstract = {In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna (R) in a prospective multicentric study. In 119/142 cases, Prosigna (R) molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping. According to local IHC, 35.4% were Luminal A-like and 64.6% Luminal B-like subtypes (local IHC+G subtype: 31.9% Luminal A-like; 68.1% Luminal B-like). In contrast to local and C1 subtyping, C6 classified >2/3 of cases as Luminal A-like. Pairwise agreement between Prosigna (R) subtyping and molecular-like subtypes was fair to moderate depending on molecular-like subtyping method and center. The best agreement was observed between Prosigna (R) (53.8% Luminal A; 44.5% Luminal B) and C1 surrogate subtyping (Cohen's kappa = 0.455). Adjuvant chemotherapy was suggested to 44.2% and 88.6% of Prosigna (R) Luminal A and Luminal B cases, respectively. Out of all Luminal A-like cases (locally IHC/IHC+G subtyping), adjuvant chemotherapy was recommended if Prosigna (R) testing classified as Prosigna (R) Luminal A at high / intermediate risk or upgraded to Prosigna (R) Luminal B.},
author = {Erber, Ramona and Angeloni, Miriam and Stöhr, Robert and Lux, Michael P. and Ulbrich-Gebauer, Daniel and Pelz, Enrico and Bankfalvi, Agnes and Schmid, Kurt W. and Walter, Robert F. H. and Vetter, Martina and Thomssen, Christoph and Mayr, Doris and Klauschen, Frederick and Sinn, Peter and Sotlar, Karl and Stering, Katharina and Stenzinger, Albrecht and Wunderle, Marius and Fasching, Peter and Beckmann, Matthias and Hoffmann, Oliver and Kimmig, Rainer and Harbeck, Nadia and Wuerstlein, Rachel and Ferrazzi, Fulvia and Hartmann, Arndt},
doi = {10.3390/ijms23158716},
faupublication = {yes},
journal = {International Journal of Molecular Sciences},
note = {CRIS-Team WoS Importer:2022-08-26},
peerreviewed = {Yes},
title = {{Molecular} {Subtyping} of {Invasive} {Breast} {Cancer} {Using} a {PAM50}-{Based} {Multigene} {Expression} {Test}-{Comparison} with {Molecular}-{Like} {Subtyping} by {Tumor} {Grade}/{Immunohistochemistry} and {Influence} on {Oncologist}'s {Decision} on {Systemic} {Therapy} in a {Real}-{World} {Setting}},
volume = {23},
year = {2022}
}
@article{faucris.259566174,
abstract = {PURPOSE: Among patients with metastatic breast cancer (mBC), the frequency of germline mutations in cancer susceptibility genes and the clinical relevance of these mutations are unclear. In this study, a prospective cohort of patients with mBC was used to determine mutation rates for breast cancer (BC) predisposition genes, to evaluate the clinical characteristics of patients with mutations, and to assess the influence of mutations on patient outcome. PATIENTS AND METHODS: Germline DNA from 2,595 patients with mBC enrolled in the prospective PRAEGNANT registry was evaluated for mutations in cancer predisposition genes. The frequencies of mutations in known BC predisposition genes were compared with results from a prospective registry of patients with nonmetastatic BC sequenced using the same QIAseq method and with public reference controls. Associations between mutation status and tumor characteristics, progression-free survival, and overall survival were assessed. RESULTS: Germline mutations in 12 established BC predisposition genes (including BRCA1 and BRCA2) were detected in 271 (10.4%) patients. A mutation in BRCA1 or BRCA2 was seen in 129 patients (5.0%). BRCA1 mutation carriers had a higher proportion of brain metastasis (27.1%) compared with nonmutation carriers (12.8%). Mutations were significantly enriched in PRAEGNANT patients with mBC compared with patients with nonmetastatic BC (10.4% v 6.6%, P < .01). Mutations did not significantly modify progression-free survival or overall survival for patients with mBC. CONCLUSION: Multigene panel testing may be considered in all patients with mBC because of the high frequency of germline mutations in BRCA1/2 and other BC predisposition genes. Although the prognosis of mutation carriers and nonmutation carriers with mBC was similar, differences observed in tumor characteristics have implications for treatment and for future studies of targeted therapies.},
author = {Fasching, Peter and Yadav, Siddhartha and Hu, Chunling and Wunderle, Marius and Häberle, Lothar and Hart, Steven N. and Rübner, Matthias and Polley, Eric C. and Lee, Kun Y. and Gnanaolivu, Rohan D. and Hadji, Peyman and Hübner, Hanna and Tesch, Hans and Ettl, Johannes and Overkamp, Friedrich and Lux, Michael P. and Ekici, Arif Bülent and Volz, Bernhard and Uhrig, Sabrina and Lüftner, Diana and Wallwiener, Markus and Müller, Volkmar and Belleville, Erik and Untch, Michael and Kolberg, Hans Christian and Beckmann, Matthias and Reis, André and Hartmann, Arndt and Janni, Wolfgang and Wimberger, Pauline and Taran, Florin Andrei and Fehm, Tanja N. and Wallwiener, Diethelm and Brucker, Sara Y. and Schneeweiss, Andreas and Hartkopf, Andreas D. and Couch, Fergus J.},
doi = {10.1200/JCO.20.01200},
faupublication = {yes},
journal = {Journal of Clinical Oncology},
note = {CRIS-Team Scopus Importer:2021-06-04},
pages = {1619-1630},
peerreviewed = {Yes},
title = {{Mutations} in {BRCA1}/2 and {Other} {Panel} {Genes} in {Patients} {With} {Metastatic} {Breast} {Cancer} -{Association} {With} {Patient} and {Disease} {Characteristics} and {Effect} on {Prognosis}},
volume = {39},
year = {2021}
}
@article{faucris.261674543,
abstract = {The number of cancer cases is increasing steadily. In Germany, 97,480 women are diagnosed with a gynecological malignancy each year, which represents 43 % of all cancer cases in women. Furthermore, gynecological malignancies are responsible for 28 % of cancer deaths. These numbers highlight the need for optimal, individualized treatment decisions in order to achieve maximum effectiveness, prevent recurrence and metastatic progression, and avoid overtreatment. Reliable and validated prognostic and predictive factors are required for the therapy decision of (neo-)adjuvant or first-line treatment of patients with gynecological cancers or breast cancer. In the era of individualized and targeted therapy there are fewer predictive factors available than originally thought. Nevertheless, future perspectives for various tumor entities present promising approaches which can support therapeutic decisions for adjuvant systemic therapy, e.g. gene expression analyses, studies of gene copy variations or the detection of single mutations which play an important role in signaling pathways of tumor cells.},
author = {Lux, Michael P. and Oenuegoeren, Onur and Wunderle, Marius and Hein, Alexander and Rauh, Claudia and Schrauder, Michael G. and Fasching, Peter and Beckmann, Matthias},
doi = {10.1007/s00129-015-3806-9},
faupublication = {no},
journal = {Gynäkologe},
keywords = {Antineoplastic agents; Biomarkers; Breast neoplasms; Decision making; Gene expression},
note = {CRIS-Team Scopus Importer:2021-07-19},
pages = {876-884},
peerreviewed = {Yes},
title = {({Neo}-){Adjuvant} and first-line therapy: {Prognostic} and predictive factors ({Neo}-){Adjuvanten} und {First}-{Line}-{Therapie}: {Prognostische} und prädiktive {Faktoren}},
volume = {48},
year = {2015}
}
@article{faucris.312688862,
abstract = {Background: High mammographic density (MD) is a risk factor for the development of breast cancer (BC). Changes in MD are influenced by multiple factors such as age, BMI, number of full-term pregnancies and lactating periods. To learn more about MD, it is important to establish non-radiation-based, alternative examination methods to mammography such as ultrasound assessments. Methods: We analyzed data from 168 patients who underwent standard-of-care mammography and performed additional ultrasound assessment of the breast using a high-frequency (12 MHz) linear probe of the VOLUSON® 730 Expert system (GE Medical Systems Kretztechnik GmbH & Co OHG, Austria). Gray level bins were calculated from ultrasound images to characterize mammographic density. Percentage mammographic density (PMD) was predicted by gray level bins using various regression models. Results: Gray level bins and PMD correlated to a certain extent. Spearman’s ρ ranged from − 0.18 to 0.32. The random forest model turned out to be the most accurate prediction model (cross-validated R 2, 0.255). Overall, ultrasound images from the VOLUSON® 730 Expert device in this study showed limited predictive power for PMD when correlated with the corresponding mammograms. Conclusions: In our present work, no reliable prediction of PMD using ultrasound imaging could be observed. As previous studies showed a reasonable correlation, predictive power seems to be highly dependent on the device used. Identifying feasible non-radiation imaging methods of the breast and their predictive power remains an important topic and warrants further evaluation. Trial registration 325-19 B (Ethics Committee of the medical faculty at Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany).},
author = {Behrens, Annika and Fasching, Peter and Schwenke, Eva and Gaß, Paul and Häberle, Lothar and Heindl, Felix and Heusinger, Katharina and Lotz, Laura and Lubrich, Hannah and Preuß, Caroline and Schneider, Michael and Schulz-Wendtland, Rüdiger and Stumpfe, Florian and Uder, Michael and Wunderle, Marius and Zahn, Anna and Hack, Carolin and Beckmann, Matthias and Emons, Julius},
doi = {10.1186/s40001-023-01327-9},
faupublication = {yes},
journal = {European Journal of Medical Research},
keywords = {Breast cancer risk; Percent mammographic density; Ultrasound},
note = {CRIS-Team Scopus Importer:2023-10-13},
peerreviewed = {Yes},
title = {{Predicting} mammographic density with linear ultrasound transducers},
volume = {28},
year = {2023}
}
@article{faucris.112985444,
abstract = {Studies of triple-negative breast cancer have recently been extending the inclusion criteria and incorporating additional molecular markers into the selection criteria, opening up scope for targeted therapies. The screening phases required for studies of this type are often prolonged, since the process of determining the molecular subtype and carrying out additional biomarker assessment is time-consuming. Parameters such as germline genotypes capable of predicting the molecular subtype before it becomes available from pathology might be helpful for treatment planning and optimizing the timing and cost of screening phases. This appears to be feasible, as rapid and low-cost genotyping methods are becoming increasingly available. The aim of this study was to identify single nucleotide polymorphisms (SNPs) for breast cancer risk capable of predicting triple negativity, in addition to clinical predictors, in breast cancer patients.This cross-sectional observational study included 1271 women with invasive breast cancer who were treated at a university hospital. A total of 76 validated breast cancer risk SNPs were successfully genotyped. Univariate associations between each SNP and triple negativity were explored using logistic regression analyses. Several variable selection and regression techniques were applied to identify a set of SNPs that together improve the prediction of triple negativity in addition to the clinical predictors of age at diagnosis and body mass index (BMI). The most accurate prediction method was determined by cross-validation.The SNP rs10069690 (TERT, CLPTM1L) was the only significant SNP (corrected p = 0.02) after correction of p values for multiple testing in the univariate analyses. This SNP and three additional SNPs from the genes RAD51B, CCND1, and FGFR2 were selected for prediction of triple negativity. The addition of these SNPs to clinical predictors increased the cross-validated area under the curve (AUC) from 0.618 to 0.625. Age at diagnosis was the strongest predictor, stronger than any genetic characteristics.Prediction of triple-negative breast cancer can be improved if SNPs associated with breast cancer risk are added to a prediction rule based on age at diagnosis and BMI. This finding could be used for prescreening purposes in complex molecular therapy studies for triple-negative breast cancer.},
author = {Häberle, Lothar and Hein, Alexander and Rübner, Matthias and Schneider, Michael and Ekici, Arif Bülent and Gaß, Paul and Hartmann, Arndt and Schulz-Wendtland, Rüdiger and Beckmann, Matthias and Lo, Wing-Yee and Schroth, Werner and Brauch, Hiltrud and Fasching, Peter and Wunderle, Marius},
doi = {10.1055/s-0043-111602},
faupublication = {yes},
journal = {Geburtshilfe und Frauenheilkunde},
note = {EVALuna2:6850},
pages = {667-678},
peerreviewed = {Yes},
title = {{Predicting} {Triple}-{Negative} {Breast} {Cancer} {Subtype} {Using} {Multiple} {Single} {Nucleotide} {Polymorphisms} for {Breast} {Cancer} {Risk} and {Several} {Variable} {Selection} {Methods}},
volume = {77},
year = {2017}
}
@article{faucris.208699252,
abstract = {BACKGROUND: It has been reported that pathological complete response is an important surrogate marker for disease-free survival and overall survival in patients with triple-negative breast cancer. This study investigates predictors of the response to neoadjuvant platinum-based or anthracycline-based treatment, and of the prognosis, in patients with triple-negative breast cancer.
METHODS: A total of 121 patients with triple-negative breast cancer received neoadjuvant treatment with either platinum or anthracycline between 2008 and 2013. Pathological complete response was assessed relative to different treatments using logistic regression models with age, clinical tumor stage, grading, and Ki-67 as predictors and interaction terms, to obtain adjusted and subgroup-specific results. The impact of the pathological complete response rate on disease-free survival and overall survival was also analyzed.
RESULTS: The pathological complete response rate was higher after platinum/taxane treatment compared with anthracycline/taxane (50.0% vs. 41.8%), but this was not significant in the adjusted analysis (OR 1.44; 95% CI, 0.68 to 3.09). A high histological grade (G3) was a predictor for higher pathological complete response in platinum-based therapy (OR 2.27; 95% CI, 1.00 to 5.30). The effect of neoadjuvant chemotherapy on pathological complete response was significantly different for G1-2 vs. G3 (Pinteraction = 0.013), and additional subgroup-specific differences were noted. Pathological complete response was a predictor for improved disease-free survival and overall survival in both treatment groups, with and without platinum chemotherapy.
CONCLUSIONS: This retrospective study of patients with triple-negative breast cancer adds to the evidence that the treatment effect of platinum may be greatest particularly in G3 tumors. In addition, the effect of pathological complete response on the prognosis does not depend on the treatment used.},
author = {Gaß, Paul and Lux, Michael P. and Rauh, Claudia and Hein, Alexander and Bani, Mayada and Fießler, Cornelia and Hartmann, Arndt and Häberle, Lothar and Pretscher, Jutta and Erber, Ramona and Wachter, David and Schulz-Wendtland, Rüdiger and Beckmann, Matthias and Fasching, Peter and Wunderle, Marius},
doi = {10.1186/s12885-018-4925-1},
faupublication = {yes},
journal = {BMC Cancer},
note = {EVALuna2:34850},
peerreviewed = {Yes},
title = {{Prediction} of pathological complete response and prognosis in patients with neoadjuvant treatment for triple-negative breast cancer},
volume = {18},
year = {2018}
}
@article{faucris.236671412,
abstract = {Breast cancer risk is reduced by number of pregnancies and breastfeeding duration, however studies of breast changes during or after pregnancy are rare. Breast volume changes - although not linked to breast cancer risk - might be an interesting phenotype in this context for correlative studies, as changes of breast volume vary between pregnant women. Serum receptor activator of nuclear factor kappa B ligand (RANKL) and its antagonist osteoprotegerin (OPG) were measured prospectively before gestational week 12, and three-dimensional breast volume assessments were performed. A linear regression model including breast volume at the start of pregnancy, RANKL, OPG, and other factors was used to predict breast volume at term. The mean breast volume was 413 mL at gestational week 12, increasing by a mean of 99 mL up to gestational week 40. In addition to body mass index and breast volume at the beginning of pregnancy, RANKL and OPG appeared to influence breast volume with a mean increase by 32 mL (P = 0.04) and a mean reduction by 27 mL (P = 0.04), respectively. Linking the RANKL/RANK/OPG pathway with breast volume changes supports further studies aiming at analysing breast changes during pregnancy with regard to breast cancer risk.},
author = {Wunderle, Marius and Rübner, Matthias and Häberle, Lothar and Schwenke, Eva and Hack, Carolin and Bayer, Christian M. and Koch, Martin and Schwitulla, Judith and Schulz-Wendtland, Rüdiger and Kozieradzki, Ivona and Lux, Michael P. and Beckmann, Matthias and Jud, Sebastian and Penninger, Josef M. and Schneider, Michael and Fasching, Peter},
doi = {10.1038/s41598-020-62070-3},
faupublication = {yes},
journal = {Scientific Reports},
note = {CRIS-Team Scopus Importer:2020-03-31},
pages = {5171-},
peerreviewed = {Yes},
title = {{RANKL} and {OPG} and their influence on breast volume changes during pregnancy in healthy women},
volume = {10},
year = {2020}
}
@article{faucris.204853569,
abstract = {Over the last two decades genetic testing for mutations in BRCA1 and BRCA2 has become standard of care for women and men who are at familial risk for breast or ovarian cancer. Currently, genetic testing more often also includes so-called panel genes, which are assumed to be moderate-risk genes for breast cancer. Recently, new large-scale studies provided more information about the risk estimation of those genes. The utilization of information on panel genes with regard to their association with the individual breast cancer risk might become part of future clinical practice. Furthermore, large efforts have been made to understand the influence of common genetic variants with a low impact on breast cancer risk. For this purpose, almost 450 000 individuals have been genotyped for almost 500 000 genetic variants in the OncoArray project. Based on first results it can be assumed that - together with previously identified common variants - more than 170 breast cancer risk single nucleotide polymorphisms can explain up to 18% of familial breast cancer risk. The knowledge about genetic and non-genetic risk factors and its implementation in clinical practice could especially be of use for individualized prevention. This includes an individualized risk prediction as well as the individualized selection of screening methods regarding imaging and possible lifestyle interventions. The aim of this review is to summarize the most recent developments in this area and to provide an overview on breast cancer risk genes, risk prediction models and their utilization for the individual patient.},
author = {Wunderle, Marius and Olmes, Gregor and Nabieva, Naiba and Häberle, Lothar and Jud, Sebastian and Hein, Alexander and Rauh, Claudia and Hack, Carolin and Erber, Ramona and Ekici, Arif Bülent and Hoyer, Juliane and Vasileiou, Georgia and Kraus, Cornelia and Reis, André and Hartmann, Arndt and Schulz-Wendtland, Rüdiger and Lux, Michael P. and Beckmann, Matthias and Fasching, Peter},
doi = {10.1055/a-0603-4350},
faupublication = {yes},
journal = {Geburtshilfe und Frauenheilkunde},
note = {EVALuna2:34612},
pages = {481-492},
peerreviewed = {Yes},
title = {{Risk}, {Prediction} and {Prevention} of {Hereditary} {Breast} {Cancer} - {Large}-{Scale} {Genomic} {Studies} in {Times} of {Big} and {Smart} {Data}},
volume = {78},
year = {2018}
}
@article{faucris.206596244,
abstract = {Background: Despite advancements in the treatment of primary and metastatic breast cancer, many patients lack a durable response to these treatments. Patients with triplenegative breast cancer (TNBC) and human epidermal growth factor receptor 2(HER2)-positive breast cancer who do not have a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) have a very poor prognosis. Tumor-infiltrating lymphocytes (TILs) have been identified as a predictive marker for pCR after NACT in TNBC and HER2-positive breast cancer. These patient populations could also be suitable for novel treatment strategies including neoepitope-based therapies. This work analyses the effect of TILs on the pCR in neoadjuvantly treated patients in the TILGen study and presents the procedures aimed at establishing neoepitope-based therapies in this study. Methods: Neoadjuvantly treated HER2positive and TNBC patients were eligible for the presented analysis concerning the association between TILs and pCR. A total of 146 patients could be identified within the TILGen study. TILs were evaluated as percentage of stromal tumor tissue in core biopsies at primary diagnosis. The phenotype 'lymphocyte-predominant breast cancer' (LPBC) was associated with pCR by logistic regression adjusted for estrogen receptor status, progesterone receptor status, HER2 status, age at diagnosis, and grading. Results: LPBC was seen in 24 (16.4%) patients. In this patient group, 66.7% achieved a pCR, while the pCR rate was 32.8% in patients with a low TIL count. The adjusted odds ratio was 6.60 (95% confidence interval 2.02-21.56; p < 0.01). Conclusion: TILs are a strong predictor of pCR in TNBC and HER2-positive breast cancer patients. Implications for the use of this information including the effect on prognosis might help to identify patients most likely to benefit from a neoepitope-based therapy approach. (C) 2018 S. Karger GmbH, Freiburg},
author = {Würfel, Franziska and Erber, Ramona and Hübner, Hanna and Hein, Alexander and Lux, Michael P. and Jud, Sebastian and Kremer, Anita and Kranich, Hannah and Mackensen, Andreas and Häberle, Lothar and Hack, Carolin and Rauh, Claudia and Wunderle, Marius and Gaß, Paul and Rabizadeh, Shahrooz and Brandl, Anna-Lisa and Langemann, Hanna and Volz, Bernhard and Nabieva, Naiba and Schulz-Wendtland, Rüdiger and Dudziak, Diana and Beckmann, Matthias and Hartmann, Arndt and Fasching, Peter and Rübner, Matthias},
doi = {10.1159/000486949},
faupublication = {yes},
journal = {Breast Care},
note = {EVALuna2:34061},
pages = {8-14},
peerreviewed = {Yes},
title = {{TILGen}: {A} {Program} to {Investigate} {Immune} {Targets} in {Breast} {Cancer} {Patients} - {First} {Results} on the {Influence} of {Tumor}-{Infiltrating} {Lymphocytes}},
volume = {13},
year = {2018}
}
@article{faucris.306488116,
abstract = {Background: Despite advancements in the treatment of primary and metastatic breast cancer, many patients lack a durable response to these treatments. Patients with triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2(HER2)-positive breast cancer who do not have a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) have a very poor prognosis. Tumor-infiltrating lymphocytes (TILs) have been identified as a predictive marker for pCR after NACT in TNBC and HER2-positive breast cancer. These patient populations could also be suitable for novel treatment strategies including neoepitope-based therapies. This work analyses the effect of TILs on the pCR in neoadjuvantly treated patients in the TILGen study and presents the procedures aimed at establishing neoepitope-based therapies in this study. Methods: Neoadjuvantly treated HER2-positive and TNBC patients were eligible for the presented analysis concerning the association between TILs and pCR. A total of 146 patients could be identified within the TILGen study. TILs were evaluated as percentage of stromal tumor tissue in core biopsies at primary diagnosis. The phenotype ‘lymphocyte-predominant breast cancer' (LPBC) was associated with pCR by logistic regression adjusted for estrogen receptor status, progesterone receptor status, HER2 status, age at diagnosis, and grading. Results: LPBC was seen in 24 (16.4%) patients. In this patient group, 66.7% achieved a pCR, while the pCR rate was 32.8% in patients with a low TIL count. The adjusted odds ratio was 6.60 (95% confidence interval 2.02-21.56; p < 0.01). Conclusion: TILs are a strong predictor of pCR in TNBC and HER2-positive breast cancer patients. Implications for the use of this information including the effect on prognosis might help to identify patients most likely to benefit from a neoepitope-based therapy approach.