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Michael P Lux, Christian M Bayer,
Christian R Loehberg,
Peter A Fasching,
Michael G Schrauder,
Mayada R Bani,
Lothar Häberle,
Anne Engel,
Katharina Heusinger,
Thorsten Tänzer,
Dragan Radosavac,
Anton Scharl,
Ingo Bauerfeind,
Judith Gesslein,
Hilde Schulte,
Brigitte Overbeck-Schulte,
Matthias W Beckmann,
Alexander Hein
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ABSTRACT: Treatment decisions in oncology are based on a balance between the efficacy of therapy and its side effects. Patients with metastases and patients with a limited prognosis are a particular challenge, since communication about the disease situation and the expected therapeutic benefit is difficult not only for patients, but also for physicians. The aim of this study was therefore to compare the benefits expected of therapy by patients and physicians. Questionnaires were sent to 9,000 breast cancer patients and to 6,938 physicians. The questionnaires described 10 cases of breast cancer in the metastatic setting. The patients and physicians were asked to state the treatment benefit they would require to decide for the therapy options chemotherapy, endocrine therapy, antibody therapy, radiotherapy, and bisphosphonates. Additionally, the participants provided data on patient and physician characteristics. Expected treatment benefits were compared between patients and physicians, and influencing factors that modified the expected benefit were identified. Patients expected much greater benefits from the therapies offered than the physicians. For all treatment modalities, about 50 % or more of patients expected more than a 12-month increase in overall survival from all therapies. Among the doctors, this proportion ranged from 7 to 30 %. Among patients, previous experience of side effects and having young children in the family were the strongest influencing factors. Among the doctors, age and level of education had a strong influence on the expected prognostic improvement to indicate a therapy option. As expectations of treatment differ greatly between patients and doctors, a structured approach to solving this conflict is required. There appear to be some indicators that might help address the problem, such as the physicians' level of training and experience and the patients' specific social circumstances.
Breast Cancer Research and Treatment 05/2013; · 4.43 Impact Factor
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Christian R Loehberg,
Katrin Almstedt,
Sebastian M Jud,
Lothar Haeberle,
Peter A Fasching,
Carolin C Hack,
Michael P Lux,
Falk C Thiel,
Michael G Schrauder,
Michaela Brunner, Christian M Bayer,
Alexander Hein,
Katharina Heusinger,
Jutta Heimrich,
Mayada R Bani,
Stefan P Renner,
Arndt Hartmann,
Matthias W Beckmann,
David L Wachter
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ABSTRACT: 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.
Breast Cancer Research and Treatment 03/2013; · 4.43 Impact Factor
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Claudia Rauh,
Florian Faschingbauer,
Lothar Haeberle,
Sebastian M Jud,
Katharina Heusinger,
Peter A Fasching,
Tamme W Goecke,
Nadeeka Rajakaruna,
Franziska Voigt,
Mayada R Bani,
Michael P Lux,
Stefan P Renner,
Christian R Loehberg,
Arndt Hartmann,
Ruediger Schulz-Wendtland,
Matthias W Beckmann, Christian M Bayer
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ABSTRACT: Pregnancy and breastfeeding are major factors reducing breast cancer (BC) risk. A potential mechanism for this effect might be changes in mammographic density, but other factors might be involved. The aim of this study was to investigate factors influencing changes in breast size and breast stiffness after pregnancy. Of a consecutive cohort of 5991 women who gave birth between 1996 and 1999, 559 replied to a questionnaire including questions about breast changes. The women completed their own assessments of changes in breast size and stiffness since their last pregnancy. Factors being investigated regarding their predictive value for these changes were: BMI before pregnancy, weight gain, age at first full-term pregnancy (FFTP), number of pregnancies, breastfeeding, and BMI of the children's fathers. A decrease in breast size was reported in 21.8% of the participants and an increase in 35.1%. With regard to the breast stiffness, 66.4% reported a decrease and only 5% reported an increase. Independent predictors for increased breast size were age at FFTP, increase in BMI since last pregnancy, BMI before pregnancy, and time since FFTP. Factors predictive of greater breast stiffness included age at FFTP, BMI before FFTP, time since FFTP, breastfeeding status, and number of pregnancies. Breast changes after pregnancy depend on several variables, which are described as BC-risk factors. Individual reaction of the female breast to a pregnancy leads to different outcomes with regard to breast size and stiffness. Further studies are needed to clarify whether these individual responses interact with the effect of pregnancy on the BC risk.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 09/2012; · 2.21 Impact Factor
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Alexander Hein,
Falk C Thiel, Christian M Bayer,
Peter A Fasching,
Lothar Häberle,
Michael P Lux,
Stefan P Renner,
Sebastian M Jud,
Michael G Schrauder,
Andreas Müller,
David Wachter,
Johanna Strehl,
Arndt Hartmann,
Matthias W Beckmann,
Claudia Rauh
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ABSTRACT: Estrogen exposure has at least a moderate effect on the risk for ovarian cancer, and antiestrogen therapy may be helpful in treating the disease. It is known from breast cancer that previous hormone replacement therapy (HRT) may influence the molecular profile and prognostic behavior of these tumors. The aim of this study was therefore to investigate the influence of previous HRT on the prognosis in a cohort of patients with invasive epithelial ovarian cancer. Among 547 patients who were treated for ovarian malignancies at a single institution from 1995 to 2008, a total of 244 postmenopausal patients with epithelial cancer and under the age of 75 were identified for whom information about HRT before the onset of the disease was available. HRT was correlated with tumor and patient characteristics. Analyses of overall survival and progression-free survival were carried out using Cox proportional hazards models. Age, tumor stage, and resection status correlated significantly with HRT in the univariate analysis. Patients with previous HRT were more likely to have a lower stage, to be younger, and to have optimal debulking. With regard to survival, HRT had a positive effect on overall survival, specifically in the subgroup of patients with optimal debulking. No correlation was seen in relation to progression-free survival. Sex hormone exposure through HRT may influence the behavior of ovarian cancers after the onset of the disease. This study supports the hypothesis that ovarian cancer is a hormonally influenced tumor.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 06/2012; · 2.21 Impact Factor
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Lothar Häberle,
Florian Wagner,
Peter A Fasching,
Sebastian M Jud,
Katharina Heusinger,
Christian R Loehberg,
Alexander Hein, Christian M Bayer,
Carolin C Hack,
Michael P Lux,
Katja Binder,
Matthias Elter,
Christian Münzenmayer,
Rüdiger Schulz-Wendtland,
Martina Meier-Meitinger,
Boris R Adamietz,
Michael Uder,
Matthias W Beckmann,
Thomas Wittenberg
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ABSTRACT: 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.
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.
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.
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.
Breast cancer research: BCR 04/2012; 14(2):R59. · 5.24 Impact Factor
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Michael G Schrauder,
Reiner Strick,
Rüdiger Schulz-Wendtland,
Pamela L Strissel,
Laura Kahmann,
Christian R Loehberg,
Michael P Lux,
Sebastian M Jud,
Arndt Hartmann,
Alexander Hein, Christian M Bayer,
Mayada R Bani,
Swetlana Richter,
Boris R Adamietz,
Evelyn Wenkel,
Claudia Rauh,
Matthias W Beckmann,
Peter A Fasching
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ABSTRACT: MicroRNAs (miRNAs, miRs) are a class of small, non-coding RNA molecules with relevance as regulators of gene expression thereby affecting crucial processes in cancer development. MiRNAs offer great potential as biomarkers for cancer detection due to their remarkable stability in blood and their characteristic expression in many different diseases. We investigated whether microarray-based miRNA profiling on whole blood could discriminate between early stage breast cancer patients and healthy controls.
We performed microarray-based miRNA profiling on whole blood of 48 early stage breast cancer patients at diagnosis along with 57 healthy individuals as controls. This was followed by a real-time semi-quantitative Polymerase Chain Reaction (RT-qPCR) validation in a separate cohort of 24 early stage breast cancer patients from a breast cancer screening unit and 24 age matched controls using two differentially expressed miRNAs (miR-202, miR-718).
Using the significance level of p<0.05, we found that 59 miRNAs were differentially expressed in whole blood of early stage breast cancer patients compared to healthy controls. 13 significantly up-regulated miRNAs and 46 significantly down-regulated miRNAs in our microarray panel of 1100 miRNAs and miRNA star sequences could be detected. A set of 240 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 78.8%, and a sensitivity of 92.5%, as well as an accuracy of 85.6%. Two miRNAs were validated by RT-qPCR in an independent cohort. The relative fold changes of the RT-qPCR validation were in line with the microarray data for both miRNAs, and statistically significant differences in miRNA-expression were found for miR-202.
MiRNA profiling in whole blood has potential as a novel method for early stage breast cancer detection, but there are still challenges that need to be addressed to establish these new biomarkers in clinical use.
PLoS ONE 01/2012; 7(1):e29770. · 4.09 Impact Factor
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Peter A Fasching,
Katharina Heusinger,
Lothar Haeberle,
Melitta Niklos,
Alexander Hein, Christian M Bayer,
Claudia Rauh,
Ruediger Schulz-Wendtland,
Mayada R Bani,
Michael Schrauder,
Laura Kahmann,
Michael P Lux,
Johanna D Strehl,
Arndt Hartmann,
Arno Dimmler,
Matthias W Beckmann,
David L Wachter
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ABSTRACT: The pathological complete response (pCR) after neoadjuvant chemotherapy is a surrogate marker for a favorable prognosis in breast cancer patients. Factors capable of predicting a pCR, such as the proliferation marker Ki67, may therefore help improve our understanding of the drug response and its effect on the prognosis. This study investigated the predictive and prognostic value of Ki67 in patients with invasive breast cancer receiving neoadjuvant treatment for breast cancer.
Ki67 was stained routinely from core biopsies in 552 patients directly after the fixation and embedding process. HER2/neu, estrogen and progesterone receptors, and grading were also assessed before treatment. These data were used to construct univariate and multivariate models for predicting pCR and prognosis. The tumors were also classified by molecular phenotype to identify subgroups in which predicting pCR and prognosis with Ki67 might be feasible.
Using a cut-off value of > 13% positively stained cancer cells, Ki67 was found to be an independent predictor for pCR (OR 3.5; 95% CI, 1.4, 10.1) and for overall survival (HR 8.1; 95% CI, 3.3 to 20.4) and distant disease-free survival (HR 3.2; 95% CI, 1.8 to 5.9). The mean Ki67 value was 50.6 ± 23.4% in patients with pCR. Patients without a pCR had an average of 26.7 ± 22.9% positively stained cancer cells.
Ki67 has predictive and prognostic value and is a feasible marker for clinical practice. It independently improved the prediction of treatment response and prognosis in a group of breast cancer patients receiving neoadjuvant treatment. As mean Ki67 values in patients with a pCR were very high, cut-off values in a high range above which the prognosis may be better than in patients with lower Ki67 values may be hypothesized. Larger studies will be needed in order to investigate these findings further.
BMC Cancer 11/2011; 11:486. · 3.01 Impact Factor
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Roger L Milne,
Ellen L Goode,
Montserrat García-Closas,
Fergus J Couch,
Gianluca Severi,
Rebecca Hein,
Zachary Fredericksen,
Núria Malats,
M Pilar Zamora,
Jose Ignacio Arias Pérez, [......],
Elza Khusnutdinova,
Marina Bermisheva,
Darya Prokofieva,
Albina Farahtdinova,
Janet E Olson,
Xianshu Wang,
Manjeet K Humphreys,
Qin Wang,
Georgia Chenevix-Trench,
Douglas F Easton
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ABSTRACT: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium.
Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression.
For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08-1.14, P = 7 × 10(-18)) for invasive breast cancer and 1.10 (95% CI = 1.01-1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99-1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12-1.20, P = 1 × 10(-18) vs. OR = 1.03, 95% CI = 0.99-1.07, P = 0.2 for PR-negative disease; P(heterogeneity) = 2 × 10(-7)); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14-1.25), 1.13 (1.09-1.16), and 1.04 (0.99-1.08) for grade 1, 2, and 3/4, respectively; P(trend) = 5 × 10(-7)].
5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer.
Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants.
Cancer Epidemiology Biomarkers & Prevention 08/2011; 20(10):2222-31. · 4.12 Impact Factor
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Katharina Heusinger,
Christian R Loehberg,
Lothar Haeberle,
Sebastian M Jud,
Peter Klingsiek,
Alexander Hein, Christian M Bayer,
Claudia Rauh,
Michael Uder,
Alexander Cavallaro,
Matthias S May,
Boris Adamietz,
Ruediger Schulz-Wendtland,
Thomas Wittenberg,
Florian Wagner,
Matthias W Beckmann,
Peter A Fasching
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ABSTRACT: Mammographic percent density (MD) is recognized as one of the strongest risk factors associated with breast cancer. This matched case-control study investigated whether MD represents an independent risk factor. Mammograms were obtained from 1025 breast cancer patients and from 520 healthy controls. MD was measured using a quantitative computer-based threshold method (0-100%). Breast cancer patients had a higher MD than healthy controls (38 vs. 32%, P<0.01). MD was significantly higher in association with factors such as age over 60 years, body mass index (BMI) of 25-30 kg/m², nulliparity or low parity (one to two births). Average MD was inversely associated with age, BMI, parity and positively associated with age at first full-term pregnancy. MD was higher in women with at least one first-degree relative affected, but only among patients and not in the group of healthy controls (P<0.01/P=0.61). In women with an MD of 25% or more, the risk of breast cancer was doubled compared with women with an MD of less than 10% (odds ratio: 2.1; 95% confidence interval: 1.3-3.4; P<0.01); in the postmenopausal subgroup, the risk was nearly tripled (odds ratio: 2.7; 95% confidence interval: 1.6-4.7; P<0.001). This study provides further evidence that MD is an important risk factor for breast cancer. These results indicate strong associations between MD and the risk of breast cancer in a matched case-control study in Germany.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 01/2011; 20(1):1-8. · 2.21 Impact Factor
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Michael G Schrauder,
Peter A Fasching,
Lothar Häberle,
Michael P Lux,
Claudia Rauh,
Alexander Hein, Christian M Bayer,
Katharina Heusinger,
Arndt Hartmann,
Johanna D Strehl,
David L Wachter,
Rüdiger Schulz-Wendtland,
Boris Adamietz,
Matthias W Beckmann,
Christian R Loehberg
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ABSTRACT: Epidemiological studies indicated that type 2 diabetes mellitus may increase breast cancer risk and mortality. The aim of this retrospective cohort study was to examine the effect of diabetes on the clinical course and the prognosis of early stage breast cancer in relation to tumour and patient characteristics.
The cohort analyzed in this study consisted of 4,056 patients with invasive primary breast cancer. We compared overall survival, distant metastasis-free survival and local recurrence free survival between breast cancer patients with and without diabetes.
In our cohort 276 breast cancer patients (6.8%) were affected by diabetes compared to 3,780 patients (93.2%) without diabetes. Women with diabetes were significantly older, had larger tumours, and a higher rate of lymph node involvement. After a follow-up period of 5 years, stratification for age and adjustment for other prognostic factors, overall mortality following breast cancer was significantly higher in diabetic breast cancer patients (hazard ratio, HR 1.92; 95% confidence interval, CI 1.49-2.48). We found no significant differences in distant metastasis-free survival and local recurrence free survival between the two groups, but we found a slightly significant higher rate of distant metastasis in the group of patients with diabetes and oestrogen receptor negative tumours (HR 2.28; CI 1.31-3.97).
In this study, patients with diabetes and oestrogen receptor negative breast cancer had a more than 2-fold higher risk for distant metastasis compared to patients without diabetes. Diabetes was also associated with an almost 2-fold increase in mortality within the 5 years follow-up period.
Journal of Cancer Research and Clinical Oncology 12/2010; 137(6):975-83. · 2.56 Impact Factor
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Christian R Loehberg,
Katharina Heusinger,
Sebastian M Jud,
Lothar Haeberle,
Alexander Hein,
Claudia Rauh,
Mayada R Bani,
Michael P Lux,
Michael G Schrauder, Christian M Bayer,
Cosima Helbig,
Ronald Grolik,
Boris Adamietz,
Ruediger Schulz-Wendtland,
Matthias W Beckmann,
Peter A Fasching
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ABSTRACT: Mammographic density (MD) has consistently been found as one of the strongest breast cancer risk factors. In our study, both qualitative and quantitative density measurements were performed in a hospital-based group of premenopausal women before and after first full-term pregnancy providing an opportunity for direct evaluation of the effects of one pregnancy on MD. Mammograms were obtained from 23 women before and after first full-term pregnancy and from 28 nulliparous controls. MD was determined by a standard qualitative assessment method using the Breast Imaging Reporting and Data System, and a quantitative computer-based threshold method (0-100%). The mean age at mammography before and after pregnancy was 31 and 34 years, respectively, with a mean difference of 40 months between mammographies. The quantitative density assessment showed a significant reduction in relative MD after pregnancy of 12 percentage points (8.6-15.4), compared with 3.1 (0.0-6.2) in the nulliparous control group (P<0.001). A reduction in MD of more than 10% was seen in 52% of the patients, compared with 18% of the controls. The qualitative density assessment confirmed a reduction in MD after pregnancy by one Breast Imaging Reporting and Data System category (P=0.02). This longitudinal study showed that MD can be influenced by one full-term pregnancy. This effect was seen with both quantitative and qualitative assessment methods. It may be hypothesized that breast cancer risk reduction associated with pregnancy is mediated through a direct reduction of MD, and MD assessment might be incorporated in individualizing risk assessment and prevention.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 11/2010; 19(6):405-12. · 2.21 Impact Factor
