R Jakesz

Medical University of Vienna, Wien, Vienna, Austria

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Publications (433)2017.27 Total impact

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    ABSTRACT: Neoadjuvant chemotherapy (NACT) is an accepted treatment approach in early-stage breast cancer. In contrast, the potential role of postneoadjuvant chemotherapy after taxane-containing NACT remains unclear. The aim of this study was to evaluate postneoadjuvant chemotherapy and further prognostic factors that predict outcome in women without pathologic complete remission (pCR). A total of 377 patients with breast cancer who received preoperative chemotherapy were included in this retrospective study. Patients without standard NACT (6 cycles of epirubicin with docetaxel) or primary metastatic breast cancer and locally advanced, inoperable cancer were excluded from further analysis (n = 186). This resulted in a study population of 191 women (30 [15.7%] with pCR; 161 [84.3%] without pCR). Major outcome parameters were event-free survival (EFS) and overall survival (OS). The following parameters were tested for their prognostic role: postneoadjuvant chemotherapy, patient age, breast cancer subtype (luminal/HER2-negative tumors, HER2-positive tumors, and triple-negative tumors), histological grade, pCR, residual lymph node invasion, and residual invasive tumor size. At a median follow-up of 54 months, 51 disease relapses (26.7%) and 21 deaths (11%) were observed. In a comparison of patients with pCR with those without, no significant differences in EFS or OS were observed. Postneoadjuvant chemotherapy was significantly associated with shorter OS in patients without pCR. In this population, which included a high percentage of patients with luminal cancers, pCR did not predict for improved OS. Postneoadjuvant chemotherapy showed no discernible benefit even in subgroups with aggressive tumor biology or significant remaining tumor burden. The use of such treatment should therefore be discouraged outside of clinical trials. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinical Breast Cancer 06/2015; DOI:10.1016/j.clbc.2015.06.007 · 2.63 Impact Factor
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    ABSTRACT: Adjuvant endocrine therapy compromises bone health in patients with breast cancer, causing osteopenia, osteoporosis, and fractures. Antiresorptive treatments such as bisphosphonates prevent and counteract these side-effects. In this trial, we aimed to investigate the effects of the anti-RANK ligand antibody denosumab in postmenopausal, aromatase inhibitor-treated patients with early-stage hormone receptor-positive breast cancer. In this prospective, double-blind, placebo-controlled, phase 3 trial, postmenopausal patients with early hormone receptor-positive breast cancer receiving treatment with aromatase inhibitors were randomly assigned in a 1:1 ratio to receive either denosumab 60 mg or placebo administered subcutaneously every 6 months in 58 trial centres in Austria and Sweden. Patients were assigned by an interactive voice response system. The randomisation schedule used a randomly permuted block design with block sizes 2 and 4, stratified by type of hospital regarding Hologic device for DXA scans, previous aromatase inhibitor use, and baseline bone mineral density. Patients, treating physicians, investigators, data managers, and all study personnel were masked to treatment allocation. The primary endpoint was time from randomisation to first clinical fracture, analysed by intention to treat. As an additional sensitivity analysis, we also analysed the primary endpoint on the per-protocol population. Patients were treated until the prespecified number of 247 first clinical fractures was reached. This trial is ongoing (patients are in follow-up) and is registered with the European Clinical Trials Database, number 2005-005275-15, and with ClinicalTrials.gov, number NCT00556374. Between Dec 18, 2006, and July 22, 2013, 3425 eligible patients were enrolled into the trial, of whom 3420 were randomly assigned to receive denosumab 60 mg (n=1711) or placebo (n=1709) subcutaneously every 6 months. Compared with the placebo group, patients in the denosumab group had a significantly delayed time to first clinical fracture (hazard ratio [HR] 0·50 [95% CI 0·39-0·65], p<0·0001). The overall lower number of fractures in the denosumab group (92) than in the placebo group (176) was similar in all patient subgroups, including in patients with a bone mineral density T-score of -1 or higher at baseline (n=1872, HR 0·44 [95% CI 0·31-0·64], p<0·0001) and in those with a bone mineral density T-score of less than -1 already at baseline (n=1548, HR 0·57 [95% CI 0·40-0·82], p=0·002). The patient incidence of adverse events in the safety analysis set (all patients who received at least one dose of study drug) did not differ between the denosumab group (1366 events, 80%) and the placebo group (1334 events, 79%), nor did the numbers of serious adverse events (521 vs 511 [30% in each group]). The main adverse events were arthralgia and other aromatase-inhibitor related symptoms; no additional toxicity from the study drug was reported. Despite proactive adjudication of every potential osteonecrosis of the jaw by an international expert panel, no cases of osteonecrosis of the jaw were reported. 93 patients (3% of the full analysis set) died during the study, of which one death (in the denosumab group) was thought to be related to the study drug. Adjuvant denosumab 60 mg twice per year reduces the risk of clinical fractures in postmenopausal women with breast cancer receiving aromatase inhibitors, and can be administered without added toxicity. Since a main side-effect of adjuvant breast cancer treatment can be substantially reduced by the addition of denosumab, this treatment should be considered for clinical practice. Amgen. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet 05/2015; DOI:10.1016/S0140-6736(15)60995-3 · 45.22 Impact Factor
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    ABSTRACT: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant inherited disorder associated with the occurrence of a wide spectrum of early-onset malignancies, the most prevalent being breast cancer and sarcoma. The presence of TP53 germline mutations in the majority of LFS patients suggests a genetic basis for the cancer predisposition. No special recommendations for the treatment of LFS patients have been made to date, except that of minimizing radiation. We hypothesized that TP53 germline mutations may be associated not only with cancer predisposition, but also with lack of response to chemo- and radiotherapy. Here, we present an Austrian LFS family whose members were intensively treated with chemo- and radiotherapy due to cancers that occurred at a predominantly young age, including eight breast cancers in six patients. Material from seven family members was screened for p53 mutation by Sanger sequencing and immunohistochemistry. A rare missense mutation in the tetramerization domain of exon 10 of the TP53 gene was found to segregate with malignant disease in this family. Lack of response to various chemotherapies and radiotherapy could be ascertained by histopathology of surgical specimens after neoadjuvant treatment, by cancer relapse occurring while receiving adjuvant systemic treatment and by the occurrence of second primaries in areas of adjuvant radiation. Our observations suggest that current standards of cancer treatment may not be valid for patients with LFS. In patients with TP53 germline mutation, cytotoxic treatment may bear not only the risk of tumor induction but also the risk of treatment failure.
    Breast Cancer Research and Treatment 05/2015; 151(3). DOI:10.1007/s10549-015-3424-1 · 4.20 Impact Factor
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    ABSTRACT: In the adjuvant treatment of hormone receptor positive (HR+) breast cancer, variables like tumour size, grade and nodal status have great impact on therapy decisions. As most node-positive patients with HR+ breast cancer currently receive adjuvant chemotherapy improved methods for characterisation of individuals' metastasis risk are needed to reduce overtreatment. Tissue specimens from node-positive patients of the ABCSG-8 and ATAC trials who received adjuvant tamoxifen and/or anastrozole were included in this study. Analysing RNA from paraffin blocks using the PAM50 test, the primary objective was to evaluate the prognostic information of the risk of recurrence (ROR) score added to combined clinical standard variables in patients with one positive node (1N+) and in patients with two or three positive nodes (2-3N+), using log-likelihood ratio tests. At a median follow-up of 9.6 years, distant metastases occurred in 97 (18%) out of 543 node positive patients. In a multivariate analysis, the PAM50-derived ROR score provided reliable prognostic information in addition to and beyond established clinical factors for 1N+ (P<0.0001) and 2-3N+ patients (P=0.0002). Ten year distant recurrence risk was significantly increased in the high risk compared to the low risk group derived from ROR score for 1N+ (25.5%, 95% CI 17.5%-36.1% vs. 6.6%, 95% CI 3.3%-12.8%) and compared to the combined low/intermediate risk group for 2-3N+ patients (33.7%, 95% CI 25.5%-43.8% vs. 12.5%, 95% CI 6.6%-22.8%). Additionally, the luminal A intrinsic subtype exhibited significantly lower risk of distant recurrence compared to the luminal B subtype in 1N+ and 2-3N+ patients. PAM50 ROR score and Intrinsic Subtype can identify node-positive patient subgroups with limited risk of metastasis after endocrine therapy, for whom adjuvant chemotherapy can be spared. The PAM50 test is a valuable tool in determining treatment for node-positive EBC patients. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Annals of Oncology 05/2015; DOI:10.1093/annonc/mdv215 · 6.58 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):S2-06-S2-06. DOI:10.1158/1538-7445.SABCS14-S2-06 · 9.28 Impact Factor
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    ABSTRACT: Introduction: Limited procedures at the T4 ganglion show low rates of compensatory sweating (CS). The aim of the study was to compare endoscopic sympathetic block (ESB) via clip application with endothoracic sympathicotomy (ETS) via diathermy with special regard on patients' quality of life (Qol). Patients and methods: Treatment success, side effects and patient satisfaction were evaluated in a prospectively gathered database of a tertiary-care referral hospital. Two disease-specific Qol questionnaires were used (Keller, Milanez de Campos). Results: 406 operations were performed in 205 patients (ESB4 N = 114, ETS4 N = 91) with a median follow-up of 12 months. Both procedures improved Qol significantly (P < 0.001) and the degree of improvement was equal in both groups. Palmar and axillary HH were ameliorated after both procedures (P < 0.001). Accordingly, plantar HH decreased after ESB4 (P = 0.002), while remaining unaltered after ETS4. Nineteen patients (9.3%) reported CS and 10 patients (4.9%) judged it as "disturbing". Nine of the latter belonged to the ETS4 group compared to one ESB patient (P = 0.015). Patients developed higher rates of plantar CS after ETS4 compared to ESB4 (P = 0.006). Five patients (2.4%) from both cohorts reported persistence of axillary HH. Recurrence of axillary symptoms was found in 5 ESB4 patients. Satisfaction rates did not differ significantly. Conclusion: Patients' Qol and satisfaction rates are similar in both treatment groups for upper limb HH. Outcome and recurrence rates speak in the favor of ETS4, severity of CS and potential reversibility argue for ESB4. Copyright © 2014. Published by Elsevier Ltd.
    International Journal of Surgery (London, England) 11/2014; 12(12):1478-1483. DOI:10.1016/j.ijsu.2014.11.018 · 1.65 Impact Factor
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    ABSTRACT: Zoledronic acid (ZOL) plus adjuvant endocrine therapy significantly improved disease-free survival (DFS) at 48 and 62 months' follow-up in the ABCSG-12 trial. We present efficacy results of a final additional analysis after 94.4 months. Patients were premenopausal women who had undergone primary surgery for stage I/II estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer with <10 positive lymph nodes, and were scheduled for standard goserelin therapy. All 1,803 patients received goserelin (3.6 mg every 28 days) and were randomized to tamoxifen (20 mg/d) or anastrozole (1 mg/d), both with or without ZOL (4 mg every 6 months) for 3 years. The primary endpoint was DFS; recurrence-free survival and overall survival (OS) were secondary endpoints. After 94.4 months' median follow-up (range, 0-114 months), relative risks of disease progression (hazard ratio [HR]=0.77; 95%CI, 0.60-0.99; P=.042) and of death (hazard ratio [HR]=0.66; 95%CI, 0.43-1.02; P=.064) are still reduced by ZOL although no longer significant at the pre-defined significance level. Overall, 251 DFS events and 86 deaths were reported. Absolute risk reductions with ZOL were 3.4% for DFS and 2.2% for OS. There was no DFS difference between tamoxifen alone versus anastrozole alone, but there was a pronounced higher risk of death for anastrozole-treated patients (HR=1.63; 95%CI, 1.05-1.45; P=.030). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. These final results from ABCSG 12 suggest that twice-yearly ZOL enhances the efficacy of adjuvant endocrine treatment, and this benefit is maintained long-term. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Annals of Oncology 11/2014; 26(2). DOI:10.1093/annonc/mdu544 · 6.58 Impact Factor
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    ABSTRACT: Background:Validated multigene signatures (MGS) provide additional prognostic information when evaluating clinical features of ER(+), HER2(-) early breast cancer. We have studied the quantitative and qualitative impact of MGS on multidisciplinary team (MDT) recommendations.Methods:We prospectively recruited 75 ER(+), HER2(-) breast cancer patients. Inclusion was based on biopsy assessment of grade, hormone receptor status, HER2, clinical tumour and nodal status. A fresh tissue sample was sent for MammaPrint (MP), TargetPrint analysis at surgery. Clinical risk was decided by the MDT in the absence of MP results and repeated following the collection of MP results. Decision changes were recorded and a health technology assessment was undertaken to compare cost effectiveness.Results:The majority of patients were assigned low to intermediate clinical risk by the MDT. According to MP, 76% were low risk. A very high correlation between local IHC and the TargetPrint assessment was shown. In over a third of patients, discordance between clinical and molecular risk was observed. Decision changes were recorded in half of these cases (18.6%) and resulted in two out of three patients not requiring chemotherapy. The use of MP was also found to be more cost effective.Conclusions:The multigene signature MP revealed clinical and molecular risk discordance in a third of patients. The impact of this on MDT recommendations was most profound in cases where few clinical risk factors were observed and enabled some women to forgo chemotherapy. The use of MGS is unlikely to have an impact in either clinically low-risk women or in patients with more than one relative indication for chemotherapy.British Journal of Cancer advance online publication, 8 July 2014; doi:10.1038/bjc.2014.339 www.bjcancer.com.
    British Journal of Cancer 07/2014; 111(5). DOI:10.1038/bjc.2014.339 · 4.82 Impact Factor
  • Cancer Research 03/2014; 73(24 Supplement):P1-08-13-P1-08-13. DOI:10.1158/0008-5472.SABCS13-P1-08-13 · 9.28 Impact Factor
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    ABSTRACT: PURPOSE: To assess the prognostic value of the PAM50 risk-of-recurrence (ROR) score on late distant recurrence (beyond 5 years after diagnosis and treatment) in a large cohort of postmenopausal, endocrine-responsive breast cancer patients.EXPERIMENTAL DESIGN: The PAM50 assay was performed on formalin-fixed paraffin-embedded whole-tumor sections of patients who had been enrolled in the Austrian Breast and Colorectal Cancer Study Group Trial 8 (ABCSG-8). RNA expression levels of the PAM50 genes were determined centrally using the nCounter Dx Analysis System. Late distant recurrence-free survival (DRFS) was analyzed using Cox models adjusted for clinical and pathologic parameters.RESULTS: PAM50 analysis was successfully performed in 1,246 ABCSG-8 patients. PAM50 ROR score and ROR-based risk groups provided significant additional prognostic information with respect to late DRFS compared with a combined score of clinical factors alone (ROR score: ΔLRχ2 15.32, P < 0.001; ROR-based risk groups: ΔLRχ2 14.83, P < 0.001). Between years 5 and 15, we observed an absolute risk of distant recurrence of 2.4% in the low ROR-based risk group, as compared with 17.5% in the high ROR-based risk group. The DRFS differences according to the PAM50 ROR score were observed for both node-positive and node-negative disease.CONCLUSION: PAM50 ROR score and ROR-based risk groups can differentiate patients with breast cancer with respect to their risk for late distant recurrence beyond what can be achieved with established clinicopathologic risk factors.
    Clinical Cancer Research 02/2014; 20(5). DOI:10.1158/1078-0432.CCR-13-1845 · 8.19 Impact Factor
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    ABSTRACT: PAM50 is a 50-gene test that is designed to identify intrinsic breast cancer subtypes and generate a Risk of Recurrence (ROR) score. It has been developed to be carried out in qualified routine hospital pathology laboratories. One thousand four hundred seventy-eight postmenopausal women with estrogen receptor (ER)+ early breast cancer (EBC) treated with tamoxifen or tamoxifen followed by anastrozole from the prospective randomized ABCSG-8 trial were entered into this study. Patients did not receive adjuvant chemotherapy. RNA was extracted from paraffin blocks and analyzed using the PAM50 test. Both intrinsic subtype (luminal A/B, HER2-enriched, basal-like) and ROR score were calculated. The primary analysis was designed to test whether the continuous ROR score adds prognostic value in predicting distant recurrence (DR) over and above standard clinical variables. In all tested subgroups, ROR score significantly adds prognostic information to the clinical predictor (P < 0.0001). PAM50 assigns an intrinsic subtype to all cases, and the luminal A cohort had a significantly lower ROR at 10 years compared with Luminal B (P < 0.0001). Significant and clinically relevant discrimination between low- and high-risk groups occurred also within all tested subgroups. The results of the primary analysis, in combination with recently published results from the ATAC trial, constitute Level 1 evidence for clinical validity of the PAM50 test for predicting the risk of DR in postmenopausal women with ER+ EBC. A 10-year metastasis risk of <3.5% in the ROR low category makes it unlikely that additional chemotherapy would improve this outcome-this finding could help to avoid unwarranted overtreatment. ABCSG 8: NCT00291759.
    Annals of Oncology 02/2014; 25(2):339-45. DOI:10.1093/annonc/mdt494 · 6.58 Impact Factor
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    ABSTRACT: There are no published data on standardized scoring systems for morbidity after breast cancer surgery. Aim of the study was to establish the Clavien Dindo Classification (CDC) as assessment tool and to identify risk factors for morbidity after breast surgery investigating new techniques including oncoplastic surgery and neoadjuvant chemotherapy. Between 2008 and 2010, data were retrospectively evaluated from 485 women with breast cancer who underwent surgery at a university hospital. The CDC was used to assess the severity of postoperative complications. Multivariable analyses were adjusted by body-mass index, smoking, diabetes mellitus and tumour size. Overall complications (CDC 1-4) were reported in 28.7%. Second surgery related to major complications (CDC 3-4) was mandatory in 4.7%. Axillary dissection was an independent predictor for CDC 1-4 in all patients (P = 0.008, OR of 1.81, 95%CI 1.17-2.82). We found no independent predictor for CDC 3-4. Oncoplastic surgery increased the rate of wound infections (P = 0.010, OR: 2.94, 95%CI 1.30-6.67) and necroses (P < 0.001, OR: 8.38, 95%CI 3.28-21.4). Axillary dissection elevated wound infection (P = 0.040, OR: 2.07, 95%CI 1.03-4.14) and seroma rates (P < 0.001, OR: 2.46, 95%CI 1.51-4.01). Neoadjuvant chemotherapy had no impact on morbidity. The CDC is a valid assessment tool for future clinical trials and may be useful for hospital quality control. While axillary dissection and oncoplastic surgery raised morbidity, no single factor predicted for morbidity related second surgery.
    International Journal of Surgery (London, England) 01/2014; 12(4). DOI:10.1016/j.ijsu.2014.01.012 · 1.65 Impact Factor
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    ABSTRACT: Introduction There are no published data on standardized scoring systems for morbidity after breast cancer surgery. Aim of the study was to establish the Clavien Dindo Classification (CDC) as assessment tool and to identify risk factors for morbidity after breast surgery investigating new techniques including oncoplastic surgery and neoadjuvant chemotherapy. Patients and methods Between 2008 and 2010, data were retrospectively evaluated from 485 women with breast cancer who underwent surgery at a university hospital. The CDC was used to assess the severity of postoperative complications. Multivariable analyses were adjusted by body-mass index, smoking, diabetes mellitus and tumour size. Results Overall complications (CDC 1–4) were reported in 28.7%. Second surgery related to major complications (CDC 3–4) was mandatory in 4.7%. Axillary dissection was an independent predictor for CDC 1–4 in all patients (P = 0.008, OR of 1.81, 95%CI 1.17–2.82). We found no independent predictor for CDC 3–4. Oncoplastic surgery increased the rate of wound infections (P = 0.010, OR: 2.94, 95%CI 1.30–6.67) and necroses (P < 0.001, OR: 8.38, 95%CI 3.28–21.4). Axillary dissection elevated wound infection (P = 0.040, OR: 2.07, 95%CI 1.03–4.14) and seroma rates (P < 0.001, OR: 2.46, 95%CI 1.51–4.01). Neoadjuvant chemotherapy had no impact on morbidity. Conclusion The CDC is a valid assessment tool for future clinical trials and may be useful for hospital quality control. While axillary dissection and oncoplastic surgery raised morbidity, no single factor predicted for morbidity related second surgery.
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    ABSTRACT: Background: This randomized phase III trial compared pathologic complete response (pCR) rates of early breast cancer (EBC) following neoadjuvant epirubicin–docetaxel (ED) ± capecitabine (C), and evaluated the addition of trastuzumab in HER2-positive tumors. Patients and methods: Patients with invasive breast cancer (except T4d) were randomly assigned to receive six 3-weekly cycles of ED (both 75 mg/m2) ± C (1000 mg/m2, twice daily, days 1–14). Patients with HER2-positive disease were further randomized to receive trastuzumab (8 mg/kg, then 6 mg/kg every 3 weeks) or not. Primary end point: pCR rate at the time of surgery. Results: Five hundred thirty-six patients were randomized to ED (n = 266) or EDC (n = 270); 93 patients were further randomized to trastuzumab (n = 44) or not (n = 49). pCR rate was significantly increased with EDC (23.0% versus 15.4% ED, P = 0.027), and nonsignificantly further increased with trastuzumab (38.6% EDC versus 26.5% ED, P = 0.212). Rates of axillary node involvement at surgery and breast conservation were improved with EDC versus ED, but not significantly; the addition of trastuzumab had no further impact. Hormone receptor status, tumor size, grade, and C (all P ≤ 0.035) were independent prognostic factors for pCR. Trastuzumab added to ED ± C significantly increased the number of serious adverse events (35 versus 18; P = 0.020), mainly due to infusion-related reactions. Conclusion: These findings show that the integration of C into a neoadjuvant taxane-/anthracycline-based regimen is a feasible, safe, and effective treatment option, with incorporation of trastuzumab in HER2-positive disease. Clinical trial number: NCT00309556, www.clinicaltrials.gov. Key words: capecitabine, docetaxel, early breast cancer, epirubicin, neoadjuvant treatment
    Annals of Oncology 12/2013; 25(2). DOI:10.1093/annonc/mdt508 · 6.58 Impact Factor
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    ABSTRACT: Background: ER+/HER2− breast cancers have a proclivity for late recurrence. A personalised estimate of relapse risk after 5 years of endocrine treatment can improve patient selection for extended hormonal therapy. Methods: A total of 1702 postmenopausal ER+/HER2− breast cancer patients from two adjuvant phase III trials (ABCSG6, ABCSG8) treated with 5 years of endocrine therapy participated in this study. The multigene test EndoPredict (EP) and the EPclin score (which combines EP with tumour size and nodal status) were predefined in independent training cohorts. All patients were retrospectively assigned to risk categories based on gene expression and on clinical parameters. The primary end point was distant metastasis (DM). Kaplan–Meier method and Cox regression analysis were used in an early (0–5 years) and late time interval (>5 years post diagnosis). Results: EP is a significant, independent, prognostic parameter in the early and late time interval. The expression levels of proliferative and ER signalling genes contribute differentially to the underlying biology of early and late DM. The EPclin stratified 64% of patients at risk after 5 years into a low-risk subgroup with an absolute 1.8% of late DM at 10 years of follow-up. Conclusion: The EP test provides additional prognostic information for the identification of early and late DM beyond what can be achieved by combining the commonly used clinical parameters. The EPclin reliably identified a subgroup of patients who have an excellent long-term prognosis after 5 years of endocrine therapy. The side effects of extended therapy should be weighed against this projected outcome.
    British Journal of Cancer 10/2013; 109(12). DOI:10.1038/bjc.2013.671 · 4.82 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate long-term results, quality of life, satisfaction and compensatory sweating after endothoracic sympathetic block at T4 (ESB4). Patients who underwent an ESB4 procedure for palmar or palmoaxillary hyperhidrosis between 2001 and 2008 were included in a prospective study at a university hospital. Questionnaires devised by Keller and Milanez de Campos were applied to evaluate disease-specific quality of life. A total of 189 patients underwent 374 ESB4 procedures. Of 174 evaluated patients, 54 (31·0 per cent) had palmar and 120 (69·0 per cent) had palmoaxillary hyperhidrosis. Median follow-up was 92 months. In both groups, treatment successfully reduced hyperhidrosis (P < 0·001) and quality of life increased significantly after ESB4 (P < 0·001), remaining stable after 5 years. Overall satisfaction rates decreased owing to the development of compensatory sweating and recurrence during follow-up. Compensatory sweating affected 41 patients (23·6 per cent), and was severe in 11 (6·7 per cent) of 163 patients at 5-year follow-up; eight of these 11 patients had been treated for palmoaxillary sweating. The severity of compensatory sweating did not deteriorate with time. The severe recurrence rate increased to 11·0 per cent during follow-up, and was twice as common in patients treated for palmoaxillary sweating as in those treated for palmar sweating (13·2 versus 6·1 per cent respectively). Nine reoperations (5·2 per cent) were performed for persistent sweating, recurrence or compensatory sweating. T4 endothoracic sympathetic clip application is safe and effective in patients with upper limb hyperhidrosis, with stable long-term improvements in quality of life.
    British Journal of Surgery 10/2013; 100(11):1471-7. DOI:10.1002/bjs.9275 · 5.21 Impact Factor
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    ABSTRACT: Background: We investigated whether body mass index (BMI) can be used as a predictive parameter indicating patients who benefit from extended aromatase inhibitor (AI) treatment. Methods: The ABCSG-6a trial re-randomised event-free postmenopausal hormone receptor-positive patients from the ABCSG-6 trial to receive either 3 additional years of endocrine therapy using anastrozole vs nil. In this retrospective analysis, we investigated the prognostic and predictive impact of BMI on disease outcome and safety. Results: In all, 634 patients (177 normal weight, 307 overweight, and 150 obese) patients were included in this analysis. Normal weight patients with additional 3 years of anastrozole halved their risk of disease recurrence (disease-free survival (DFS) HR 0.48; P=0.02) and death (HR 0.45; P=0.06) and had only a fifth of the risk of distant metastases (HR 0.22; P=0.05) compared with normal weight patients without any further treatment. In contrast, overweight+obese patients derived no benefit from additional 3 years of anastrozole (DFS HR 0.93; P=0.68; distant recurrence-free survival HR 0.91; P=0.78; and OS HR 0.9; P=0.68). The possible predictive impact of BMI on extended endocrine treatment could be strengthened by a Cox regression interaction model between BMI and treatment (P=0.07). Conclusion: Body mass index may be used to predict outcome benefit of extended AI treatment in patients with receptor-positive breast cancer.
    British Journal of Cancer 07/2013; 109(3). DOI:10.1038/bjc.2013.367 · 4.82 Impact Factor
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    ABSTRACT: Background: There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospective study population of the ABCSG-06 trial. Methods: ABCSG-06 investigated the efficacy of tamoxifen vs tamoxifen plus aminoglutethimide in postmenopausal women with hormone receptor-positive breast cancer. Taking BMI at baseline, patients were classified as normal weight (BMI=18.5–24.9 kg m−2), overweight (BMI=25–29.9 kg m−2), and obese (30 kg m−2) according to WHO criteria. Results: Overweight+obese patients had an increased risk for distant recurrences (hazard ratio (HR): 1.51; Cox P=0·018) and a worse overall survival (OS; HR: 1·49; Cox P=0·052) compared with normal weight patients. Analysing patients treated with single tamoxifen only, no difference between overweight+obese patients and normal weight patients regarding distant recurrence-free survival (HR: 1.35; Cox P=0·24) and OS (HR: 0.99; Cox P=0·97) could be observed. In contrast, in the group of patients treated with the combination of tamoxifen plus aminoglutethimide, overweight+obese patients had an increased risk for distant recurrences (1.67; Cox P=0·03) and a worse OS (1.47; Cox P=0·11) compared with normal weight patients. Conclusion: BMI impacts on the efficacy of aromatase inhibitor-based treatment but not single tamoxifen.
    British Journal of Cancer 03/2013; 108(7). DOI:10.1038/bjc.2013.114 · 4.82 Impact Factor
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    ABSTRACT: Background In women with node-positive breast cancer, the Breast International Group (BIG) 02-98 tested the incorporation of docetaxel (Taxotere) into doxorubicin (Adriamycin)-based chemotherapy, and compared sequential and concurrent docetaxel. At 5 years, there was a trend for improved disease-free survival (DFS) with docetaxel. We present results at 8-year median follow-up and exploratory analyses within biologically defined subtypes.Methods Patients were randomly assigned to one of four treatments: (i) sequential control: doxorubicin (A) (75 mg/m(2)) × 4 →classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF); (ii) concurrent control: doxorubicin, cyclophosphamide (AC)(60/600 mg/m(2)) × 4 →CMF; (iii) sequential docetaxel: A (75 mg/m(2)) × 3 → docetaxel (T) (100 mg/m(2)) × 3 → CMF and (iv) concurrent docetaxel: AT(50/75 mg/m(2)) × 4 →CMF. The primary comparison evaluated docetaxel efficacy regardless of the schedule. Exploratory analyses were undertaken within biologically defined subtypes.ResultsTwo thousand eight hundred and eighty-seven patients were enrolled. After 93.4 months of median follow-up, there were 916 DFS events. For the primary comparison, there was no significant improvement in DFS from docetaxel [hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.80-1.05, P = 0.187]. In secondary comparisons, sequential docetaxel significantly improved DFS compared with sequential control (HR = 0.81, 95% CI = 0.67-0.99, P = 0.036), and significantly improved DFS (HR = 0.84, 95% CI = 0.72-0.99, P = 0.035) and overall survival (OS) (HR = 0.79, 95% CI = 0.65-0.98, P = 0.028) compared with concurrent doxorubicin-docetaxel. Luminal-A disease had the best prognosis. HRs favored addition of sequential docetaxel in all subtypes, except luminal-A; but this observation was not statistically supported because of limited numbers.Conclusion With further follow-up, the sequential docetaxel schedule resulted in significantly better OS than concurrent doxorubicin-docetaxel, and continued to show better DFS than sequential doxorubicin-based control.
    Annals of Oncology 01/2013; 24(5). DOI:10.1093/annonc/mds627 · 6.58 Impact Factor
  • Cancer Research 12/2012; 72(24 Supplement):P2-10-02-P2-10-02. DOI:10.1158/0008-5472.SABCS12-P2-10-02 · 9.28 Impact Factor

Publication Stats

11k Citations
2,017.27 Total Impact Points

Institutions

  • 1981–2015
    • Medical University of Vienna
      • • Comprehensive Cancer Center Vienna
      • • Department of Radiology
      • • Institute for Social Medicine
      • • Klinisches Institut für Pathologie
      Wien, Vienna, Austria
  • 1999–2011
    • Vienna General Hospital
      Wien, Vienna, Austria
  • 1976–2011
    • University of Vienna
      • • Department of Surgery
      • • Universitätsklinik für Innere Medizin I
      • • Department of Clinical Pathology
      Wien, Vienna, Austria
  • 2010
    • НИИ онкологии им.Н.Н. Петрова
      Sankt-Peterburg, St.-Petersburg, Russia
  • 2000–2008
    • IST Austria
      Klosterneuberg, Lower Austria, Austria
  • 2007
    • Paracelsus Medical University Salzburg
      Salzburg, Salzburg, Austria
  • 2005
    • University of Oxford
      Oxford, England, United Kingdom
    • John Wayne Cancer Institute
      Santa Monica, California, United States
    • University of Hamburg
      Hamburg, Hamburg, Germany
  • 2002–2005
    • Karl-Franzens-Universität Graz
      Gratz, Styria, Austria
  • 2003
    • Regional Hospital Wiener Neustadt
      Wiener Neustadt, Lower Austria, Austria
  • 1997
    • National Defense Medical College
      • Division of Obstetrics and Gynecology
      Tokorozawa, Saitama, Japan
  • 1996
    • University of Innsbruck
      Innsbruck, Tyrol, Austria
  • 1986
    • National Cancer Institute (USA)
      Maryland, United States
  • 1985
    • NCI-Frederick
      Фредерик, Maryland, United States
  • 1983
    • Moncrief Cancer Institute
      Fort Worth, Texas, United States