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  • 1
    Keywords: EXPRESSION ; IONIZING-RADIATION ; SURVIVAL ; tumor ; DIAGNOSIS ; FOLLOW-UP ; COHORT ; GLUTATHIONE ; METALLOTHIONEIN ; GENOME-WIDE ASSOCIATION
    Abstract: We assessed whether variants in 22 oxidative stress-related genes are associated with mortality of breast cancer patients and whether the associations differ according to radiotherapy. Using a prospective cohort of 1348 postmenopausal breast cancer patients, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for 109 single nucleotide polymorphisms (SNPs) using Cox proportional hazards regression. Validation of results was attempted using two Scandinavian studies. Eleven SNPs in MT2A, NFE2L2, NQO1, PRDX1, and PRDX6 were significantly associated with overall mortality after a median follow-up of 5.7 years. Three SNPs in NQO1 (rs2917667) and in PRDX6 (rs7314, rs4916362) were consistently associated with increased risk of dying across all three study populations (pooled: HRNQO1_rs2917667 1.20, 95% CI 1.00-1.44, p = 0.051; HRPRDX6_rs7314 1.16, 95% CI 1.00-1.35, p = 0.056, HRPRDX6_rs4916362 1.14 95% CI 1.00-1.32, p = 0.062). Potential effect modification by radiotherapy was found for CAT_rs769218. In conclusion, genetic variants in NQO1 and PRDX6 may modify breast cancer prognosis.
    Type of Publication: Journal article published
    PubMed ID: 23489758
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  • 2
    Abstract: Iran is rapidly becoming an "ageing society" with a related increase in cancer incidence including breast cancer. This paper evaluates the trend in breast cancer incidence from the past to the present, in order to predict the future burden in Iran and to quantify the effect of changes in known risk factors on incidence over time. Currently, breast cancer incidence in Iran is low with approximately 5000 new cases annually. Under conservative assumptions, the number of new cases of breast cancer in 2030 will be more than 15000. In addition to demographic factors, changes in the prevalence of established risk factors such as reproductive factors and obesity are likely to result in changes in breast cancer patients over time. Extrapolating the increasing prevalence of obesity to the future, we expect that this specific factor will strongly contribute to the increased breast cancer incidence in the future unless preventive measures counteract this effect.
    Type of Publication: Journal article published
    PubMed ID: 22835919
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  • 3
    Abstract: Increased proliferation is a hallmark of malignant tumors. The proliferation marker Ki67 has been investigated as a breast cancer biomarker, but despite 32 years of research the best cutpoints and the best methods for determination are still under debate. This review is based on an overview on the efforts to standardize Ki67 and to optimize its performance that was presented at the St. Gallen oncology conference 2015. The clinical validity of Ki67 as a prognostic marker as well as a predictive marker (in the neoadjuvant setting) has been shown in several meta-analyses. Depending on cohort characteristics, molecular subtype and clinical setting, Ki67 is a prognostic marker, a predictive marker, or both. Many different cutpoints for Ki67 have been reported, but it is has not been possible to determine an evidence-based "optimal" cutpoint. This supports the view that Ki67 is continuous marker, reflecting the continuous variation of the proliferation rate in different tumors. We should probably stop looking for an "optimal" cutpoint for Ki67 because it simply does not exist. It is evident from the results of several ring trials that intermediate levels of Ki67 are particularly difficult for standardization. Due to the low analytical validity in the intermediate range as well as intratumoral heterogeneity, the clinical utility of intermediate Ki67 levels is limited. Clinical decisions should not be based on small differences in the intermediate range and additional molecular tests might be necessary for tumors with intermediate Ki67 levels. For the two groups of tumors with a very low or a very high Ki67 a clinical interpretation could be straightforward. Despite these limitations, the assessment of proliferation is a central parameter for tumor characterization and an important element of the pathological assessment.
    Type of Publication: Journal article published
    PubMed ID: 26283598
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  • 4
    Abstract: Neoadjuvant therapy is very often an adequate alternative to adjuvant therapy. This review is summarizing the recent advances made in the area of neoadjuvant therapy in breast cancer. The focus will lie on recently published clinical trials but will not further highlight surgical, imaging and radiooncological issues related to neoadjuvant therapy. RECENT FINDINGS: Within the last 1-1.5 years it has been discussed if neoadjuvant treatment can be used as faster way to get access to new therapies, based on new data in HER2+ breast cancer suggesting a higher pCR rate when a dual anti-HER2 therapy was used. Nevertheless this higher pCR rate does not necessarily translate always into a better survival. In TNBC carboplatin could be identified as an asset for patients, especially in patients with gBRCA mutations. However, mature long term data are still missing. The neoadjuvant approach is ideal to identify new biomarkers which predict response or resistance to the given treatment. Tumour infiltrating lymphocytes and PIK3CA mutations are amongst the most promising markers. SUMMARY: Neoadjuvant treatment should be considered for all patients with HER2-positive or triple negative breast cancer. Clinical trials in this setting are currently investigating new approaches.
    Type of Publication: Journal article published
    PubMed ID: 26387601
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  • 5
    Keywords: CANCER ; tumor ; FOLLOW-UP ; RISK ; TIME ; INFECTION ; breast cancer ; MICROMETASTASES ; PROGNOSTIC-SIGNIFICANCE ; body mass index ; PAIN ; ISOLATED TUMOR-CELLS ; ASPIRATION ; BIOPSY MORBIDITY ; Bone marrow puncture ; DTCs ; PRIMARY SURGERY ; Side-effects
    Abstract: BACKGROUND AND AIM: In breast cancer patients, intraoperative bone marrow puncture (BMP) with positive detection of disseminated tumor cells has been reported to predict unfavorable clinical outcome due to increased risk of recurrence. In this study, we prospectively assessed BMP-associated untoward side-effects. METHODS: Fifty-eight consecutive breast cancer patients were prospectively explored after intraoperative BMP for postoperative pain (visual analogue scale, VAS) and complications in terms of infection, hematoma, and sensibility disorder. Furthermore, the impact of BMP on hospital stay duration was analyzed in 254 patients. RESULTS: In all subgroups analyzed, during five postoperative days patients complained about minor pain only at the site of BMP (VAS 〈 1) while the corresponding pain scores were significantly higher for the area of the operated breast. Post-BMP iliac crest hematomas were encountered in 13 out of 58 patients (22.4%) who were significantly older (p = 0.04), less frequently smokers (p = 0.02), and presented with higher body mass index (p = 0.01) than controls. Within the area of BMP no signs of infection or sensibility disorders were observed. Comparison of patients with and without BMP did not show any significant difference in postoperative hospital stay duration. CONCLUSION: Referring to the potential clinical benefit of intraoperative BMP its prospectively assessed adverse side-effects appear relatively mild and thus acceptable.
    Type of Publication: Journal article published
    PubMed ID: 20621481
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  • 6
    Keywords: SURVIVAL ; Germany ; DIAGNOSIS ; POPULATION ; statistics ; EUROPE ; PERIOD ANALYSIS ; PROGRESS ; EUROCARE-4 ; 21ST-CENTURY
    Abstract: INTRODUCTION: Evaluation of oncological outcome and prognostic factors of patients with primary breast cancer treated at a certified academic breast unit. PATIENTS AND METHODS: We prospectively collected data of 3338 patients, diagnosed with primary breast cancer between 01.01.2003 and 31.12.2010 and treated at the Breast Unit Heidelberg, Germany, in order to analyze outcome in clinical practice. We evaluated local control rate (LCR), disease-free survival (DFS), distant disease-free survival (DDFS), observed overall survival (OS) and age-adjusted relative overall survival (ROS). In addition, the impact of known prognostic factors on these outcome variables was examined in univariate and multivariate analyses. RESULTS: Of all patients, 368 (11.0%) had carcinoma in situ (CIS) and 197 (5.9%) had bilateral cancers. For the 2970 patients with invasive cancer, of which 49 patients (1.7%) had metastastic disease at time of diagnosis, DFS, LCR, DDFS, OS and ROS at 5 years were 79.8%, 84.7%, 81.2%, 86.3%, and 89.8%, respectively. In multivariate analysis age, pT category, nodal status, hormone receptor status and grading were identified as independent prognostic factors for OS. CONCLUSION: Compared with recent population-based reports from Germany, more favourable patient characteristics and nominally higher survival was found among this large cohort of patients with primary breast cancer treated at a single certified breast unit.
    Type of Publication: Journal article published
    PubMed ID: 22310244
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  • 7
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    Breast 22 (Suppl. 2), S66-72 
    Keywords: UP-REGULATION ; DUCTAL CARCINOMA ; CARCINOMA IN-SITU ; MAMMARY EPITHELIAL-CELLS ; BONE METASTASES ; OSTEOPONTIN EXPRESSION ; LYSYL OXIDASE ; TENASCIN-C ; PLASMINOGEN/PLASMIN SYSTEM ; HYALURONAN RECEPTORS
    Abstract: The extracellular matrix (ECM) is composed of highly variable and dynamic components that regulate cell behavior. The protein composition and physical properties of the ECM govern cell fate through biochemical and biomechanical mechanisms. This requires a carefully orchestrated and thorough regulation considering that a disturbed ECM can have serious consequences and lead to pathological conditions like cancer. In breast cancer, many ECM proteins are significantly deregulated and specific matrix components promote tumor progression and metastatic spread. Intriguingly, several ECM proteins that are associated with breast cancer development, overlap substantially with a group of ECM proteins induced during the state of tissue remodeling such as mammary gland involution. Fibrillar collagens, fibronectin, hyaluronan and matricellular proteins are matrix components that are common to both involution and cancer. Moreover, some of these proteins have in recent years been identified as important constituents of metastatic niches in breast cancer. In addition, specific ECM molecules, their receptors or enzymatic modifiers are significantly involved in resistance to therapeutic intervention. Further analysis of these ECM proteins and the downstream ECM mediated signaling pathways may provide a range of possibilities to identify druggable targets against advanced breast cancer.
    Type of Publication: Journal article published
    PubMed ID: 24074795
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  • 8
    Keywords: COHORT ; INDEX ; OBESITY ; C-REACTIVE PROTEIN ; nutrition ; ADULTS ; HEALTH CONDITIONS
    Abstract: Unhealthy dietary habits can increase the risk for serious medical conditions, such as cancer, yet the association between diet and breast cancer remains unclear. We investigated whether individual diets based on their inflammatory potential are associated with postmenopausal breast cancer risk by employing an energy-adjusted dietary inflammation index. In a German population-based case-control study, 2887 postmenopausal breast cancer patients (aged 50-74 years, first diagnosed between 2002 and 2005) and 5512 healthy age-matched controls provided information on dietary habits for the year prior to diagnosis (cases) or recruitment (controls) using a 176-items food frequency questionnaire. Associations between the energy-adjusted dietary inflammation index (E-DII) score (both as continuous variable and in quintiles) and risk for breast cancer were assessed using conditional logistic regression adjusted for potential confounders. No significant associations between the E-DII score and postmenopausal breast cancer risk were observed (adjusted OR Q5 vs Q1: 1.01, 95% CI: 0.86-1.17). Associations did not differ by estrogen receptor/progesterone receptor status (ER + PR+: adjusted OR Q5 vs Q1: 1.06, 95% CI: 0.88-1.27; ER + or PR+: OR Q5 vs Q1: 1,07, 95% CI: 0.79-1.45; ER-PR-: OR Q5 vs Q1: 0.87 95% CI: 0.63-1.20). Our results regarding E-DII are consistent with previous studies reporting a lack of association between C-reactive protein, a marker of systemic inflammation, and postmenopausal breast cancer risk. The findings may reflect a real absence of association between dietary inflammatory potential and postmenopausal cancer risk or an underestimation of association due to recall bias. Further investigation is warranted in cohort studies.
    Type of Publication: Journal article published
    PubMed ID: 25987487
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  • 9
    Abstract: BACKGROUND: Studies of cohorts of breast cancer (BC) patients diagnosed before 1990 showed radiotherapy (RT) to be associated with increased cardiovascular (CVD) and lung cancer mortality many years after diagnosis. In the late 1990s, improvements in RT planning techniques reduced radiation doses to normal tissues. Recent studies did not consistently report higher RT-related mortality for CVD and second cancers. Aim of the study was to analyze specific causes of death after 3D-conformal RT in a recent BC cohort. METHODS: Stage I-III BC patients diagnosed 2001-2005 and enrolled in the population based MARIEplus study were followed-up for 11.9 years (median). Associations between adjuvant RT and cause-specific mortality were analyzed by using competing risks models, yielding subdistribution hazard ratios (SHR) for RT directly related to cumulative incidences. Models were adjusted for differences in baseline characteristics applying inverse-probability-of-treatment-weighting (IPTW). RESULTS: Of the 2951 patients, 2439 (83.0%) received RT. No significant association of RT with lung cancer mortality (SHRIPTW 0.88, 0.35-2.12), other cancer mortality (SHRIPTW 1.04, 95% CI 0.62-1.73) or cardiac mortality was observed (SHRIPTW 1.57, 0.75-3.29). Mortality from lung and other diseases were significantly lower in irradiated women (SHRIPTW 0.39, 95% CI 0.17-0.90 and SHRIPTW 0.58, 95% CI 0.34-0.97, respectively). CONCLUSION: In line with recent studies, 3D-conformal RT did not significantly increase mortality from non-BC causes in the German MARIEplus cohort. Since long-term data are still sparse and event rates low in BC-cohorts, who received modern RT, investigation of possible late RT effects on mortality beyond 14 years of follow-up is warranted.
    Type of Publication: Journal article published
    PubMed ID: 29248876
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  • 10
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