G G Steger

Medical University of Vienna, Wien, Vienna, Austria

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Publications (308)1399.34 Total impact

  • Michael Gnant, Guenther G Steger, Rupert Bartsch
    The Lancet Oncology 12/2014; · 25.12 Impact Factor
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    ABSTRACT: In a longitudinal observation, extravasation of antitumoural compounds and the efficacy of its structured interdisciplinary management were assessed in a routine setting. One hundred sixty-nine patients with extravasation of cytotoxics were managed according to a prospective approach documenting the extravasated compound, localisation, duration until full symptom resolution and sequelae. Surgery was implemented in the case of failure of conservative measures. In 155 (91.7 %) out of 169 patients, conservative management was successful (surgical intervention, 14 patients). Extravasations of anthracyclines (N = 44), platinum compounds (N = 41), vinca alkaloids (N = 20) and taxanes (N = 19) were often associated with erythema, oedema and pain. The median period until full resolution of symptoms differed among the administered cytotoxics (anthracyclines, 55 days; taxanes and vinca alkaloids, 27 days; platinum compounds, 14 days) with statistical significance between the vesicants. Histologically, surgically resected specimens showed extensive necrotic areas with inflammatory infiltrates at the periphery of the removed lesions. In a routine setting, the standardised management of cytotoxic extravasations by an interdisciplinary task force resulted in a satisfactory outcome. When surgical intervention was indicated, complete remission of the lesions within a median of 14 days reduced the delay in the administration of further chemotherapy to a minimum. The proposed approach is therefore considered as suitable to manage extravasations in cancer chemotherapy in a large number of subjects and to ensure patient adherence to cytotoxic treatment.
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 11/2014;
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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 : official journal of the European Society for Medical Oncology / ESMO. 11/2014;
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    ABSTRACT: Recently, HER3-expression was postulated as independent risk factor for metastatic spread. Therefore, we investigated the role of HER3 expression as prognostic marker in metastatic breast cancer patients.
    Breast (Edinburgh, Scotland) 07/2014; · 2.09 Impact Factor
  • Annals of Oncology 05/2014; 25 Suppl 1:i13. · 7.38 Impact Factor
  • Michael Gnant, Rupert Bartsch, Guenther G Steger
    The Lancet Oncology 05/2014; · 25.12 Impact Factor
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    ABSTRACT: Triple-negative breast cancer (TNBC) patients without pathological complete response (pCR) to neoadjuvant chemotherapy have an unfavourable prognosis. TNBC harbouring BRCA-1 germline mutations may be less responsive to taxanes, while sensitivity to DNA-damaging agents is retained. A similar effect was seen in tumours with epigenetic BRCA-1 silencing. Patients without pCR to neoadjuvant chemotherapy consisting of epirubicin plus docetaxel routinely received post-operative CMF at our centre. Here, we investigated the effect of adjuvant CMF in patients with or without BRCA-1 methylation or TP53 mutation. DNA was extracted from formalin-fixed paraffin-embedded tissue. For determining BRCA-1 methylation status, quantitative methylation-specific PCR was performed. For the investigation of TP53 mutation status, DNA was PCR amplified and sequenced by Sanger sequencing. Twenty-four patients were included; BRCA-1 methylation was present in 41.7 %, while TP53 mutations were observed in 66.7 %. At a median follow-up of 27.5 months, 20 % of patients with BRCA-1 methylation had a disease-free survival (DFS) event, as compared to 64.3 % in the non-methylated group (p = 0.0472). Median DFS in the non-methylated group was 16 months and was not reached in the methylated group (n.s.). No association TP53 mutation status with clinical outcome was observed. Adjuvant CMF is of limited activity in TNBC refractory to taxane-based neoadjuvant chemotherapy. In this population, BRCA-1 methylation was associated with a significant decrease in DFS events suggesting a better prognosis and potentially retained activity of DNA-damaging agents.
    Cancer Chemotherapy and Pharmacology 02/2014; · 2.80 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. · 7.38 Impact Factor
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    ABSTRACT: Extravasation of cytotoxic drugs is a serious complication of systemic cancer treatment. Still, a reliable method for early assessment of tissue damage and outcome prediction is missing. Here, we demonstrate that the evaluation of blood flow by indocyanine green (ICG) angiography in the extravasation area predicts for the need of surgical intervention.
    PLoS ONE 01/2014; 9(8):e103649. · 3.53 Impact Factor
  • The Breast. 01/2014;
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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; · 7.38 Impact Factor
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    ABSTRACT: Monoclonal antibodies (mAb), such as trastuzumab are a valuable addition to breast cancer therapy. Data obtained from neoadjuvant settings revealed that antibody-dependent cell-mediated cytotoxicity (ADCC) is a major mechanism of action for the mAb trastuzumab. Conflicting results still call into question whether disease progression, prolonged treatment or concomitant chemotherapy influences ADCC and related immunological phenomena. We analyzed the activity of ADCC and antibody-dependent cell-mediated phagocytosis (ADCP) of peripheral blood mononuclear cells (PBMCs) from human epidermal growth factor receptor 2 (HER2/neu) positive breast cancer patients receiving trastuzumab therapy either in an adjuvant (n = 13) or metastatic (n = 15) setting as well as from trastuzumab treatment-naive (t-naive) HER2/neu negative patients (n = 15). PBMCs from healthy volunteers (n = 24) were used as controls. ADCC and ADCP activity was correlated with the expression of antibody binding Fc-gamma receptor (FcgammaR)I (CD64), FcgammaRII (CD32) and FcgammaRIII (CD16) on CD14+ (monocytes) and CD56+ (NK) cells, as well as the expression of CD107a + (LAMP-1) on CD56+ cells and the total amount of CD4 + CD25 + FOXP3+ (Treg) cells. In metastatic patients, markers were correlated with progression-free survival (PFS). ADCC activity was significantly down regulated in metastatic, adjuvant and t-naive patient cohorts as compared to healthy controls. Reduced ADCC activity was inversely correlated with the expression of CD107a on CD56+ cells in adjuvant patients. ADCC and ADCP activity of the patient cohorts were similar, regardless of treatment duration or additional chemotherapy. PFS in metastatic patients inversely correlated with the number of peripheral Treg cells. The reduction of ADCC in patients as compared to healthy controls calls for adjuvant strategies, such as immune-enhancing agents, to improve the activity of trastuzumab. However, efficacy of trastuzumab-specific ADCC and ADCP appears not to be affected by treatment duration, disease progression or concomitant chemotherapy. This finding supports the application of trastuzumab at any stage of the disease.
    Journal of Translational Medicine 12/2013; 11(1):307. · 3.46 Impact Factor
  • International journal of clinical pharmacology and therapeutics 11/2013; · 1.20 Impact Factor
  • International journal of clinical pharmacology and therapeutics 11/2013; · 1.20 Impact Factor
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    ABSTRACT: Summary In patients with hormone receptor-positive advanced breast cancer, response to endocrine therapy is frequently limited by endocrine resistance. One important mechanism of resistance is related to mammalian target of rapamycin (mTOR), a molecule involved in the activation of alternative signaling pathways. Preclinically, resensitization of endocrine resistance can be achieved by the addition of the mTOR inhibitor everolimus to endocrine therapy. Recent results of clinical trials confirmed the clinical activity of combining everolimus and endocrine therapy in neoadjuvant and advanced breast cancer. The BOLERO-2 trial demonstrated significant progression-free survival benefits for the addition of everolimus to exemestane. These data were the basis for the recent approval of everolimus in combination with exemestane for the treatment of advanced hormone receptor- positive breast cancer. In clinical practice, the following 3 patient groups are particularly suitable for this treatment: those with progression on aromatase inhibitor therapy, those who respond well to chemotherapy and might benefit from subsequent endocrine therapy, and those with non-aggressive tumor biology. Everolimus treatment requires careful clinical monitoring due to the potentially serious side effects, e.g. stomatitis and pneumonitis. It is also important to educate patients and physicians in order to increase their awareness of side effects. At present, everolimus is investigated in clinical trials.
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    ABSTRACT: Schlüsselwörter Mammakarzinom, fortgeschrittenes · Endokrine Therapie · Endokrine Resistenz · mTOR-Hemmung · Everolimus · Exemestan Zusammenfassung Aufgrund von endokriner Resistenz sprechen Patientinnen mit Hormonrezeptor-positivem Mammakarzinom häufig nur bedingt auf antihormonelle Therapien an. Ein wichtiger Re-sistenzmechanismus wird durch mTOR (mammalian target of rapamycin) vermittelt, ein Molekül mit zentraler Funktion in der Aktivierung alternativer Signalwege innerhalb der Tumorzellen. Unter präklinischen Bedingungen kann durch den mTOR-Inhibitor Everolimus eine Resensibilisierung er-reicht werden. Außerdem bestätigen klinische Studien die klinische Wirksamkeit der kombinierten Verabreichung von Everolimus und der endokrinen Therapie im neoadjuvanten und fortgeschrittenen Setting. Die Studie BOLERO-2 de-monstrierte signifikante und relevante Verbesserungen des progressionsfreien Überlebens durch die Zugabe von Eve-rol imus zu Exemestan. Diese Daten bilden die Basis für die kürzlich erfolgte Zulassung der Kombination aus Everoli-mus und Exemestan für die Behandlung des fortgeschritte-nen Hormonrezeptor-positiven Mammakarzinoms nach dem Versagen von Aromatasehemmern. In der klinischen Praxis eignen sich 3 Patientinnengruppen besonders für diese Therapie: Patientinnen mit Progression unter Aroma-stasehemmern, solche mit gutem Ansprechen auf Chemo-therapie und antihormonelle Folgetherapie sowie solche mit nicht aggressiver Tumorbiologie. Aufgrund der poten-ziell schweren Nebenwirkungen, z.B. Stomatitis und Pneu-monitis, setzt die Therapie mit Everolimus eine sorgfältige klinische Überwachung voraus. Aufklärung und Bewusst-seinsbildung hinsichtlich der Nebenwirkungen bei Ärzten und Patienten sind für ein optimales Therapiemanagement entscheidend. Derzeit wird Everolimus in weiteren klini-schen Studien untersucht.
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    ABSTRACT: The addition of bevacizumab to chemotherapy improves progression-free survival in metastatic breast cancer and pathological complete response rates in the neoadjuvant setting. Micrometastases are dependent on angiogenesis, suggesting that patients might benefit from anti-angiogenic strategies in the adjuvant setting. We therefore assessed the addition of bevacizumab to chemotherapy in the adjuvant setting for women with triple-negative breast cancer. For this open-label, randomised phase 3 trial we recruited patients with centrally confirmed triple-negative operable primary invasive breast cancer from 360 sites in 37 countries. We randomly allocated patients aged 18 years or older (1:1 with block randomisation; stratified by nodal status, chemotherapy [with an anthracycline, taxane, or both], hormone receptor status [negative vs low], and type of surgery) to receive a minimum of four cycles of chemotherapy either alone or with bevacizumab (equivalent of 5 mg/kg every week for 1 year). The primary endpoint was invasive disease-free survival (IDFS). Efficacy analyses were based on the intention-to-treat population, safety analyses were done on all patients who received at least one dose of study drug, and plasma biomarker analyses were done on all treated patients consenting to biomarker analyses and providing a measurable baseline plasma sample. This trial is registered with ClinicalTrials.gov, number NCT00528567. Between Dec 3, 2007, and March 8, 2010, we randomly assigned 1290 patients to receive chemotherapy alone and 1301 to receive bevacizumab plus chemotherapy. Most patients received anthracycline-containing therapy; 1638 (63%) of the 2591 patients had node-negative disease. At the time of analysis of IDFS, median follow-up was 31·5 months (IQR 25·6-36·8) in the chemotherapy-alone group and 32·0 months (27·5-36·9) in the bevacizumab group. At the time of the primary analysis, IDFS events had been reported in 205 patients (16%) in the chemotherapy-alone group and in 188 patients (14%) in the bevacizumab group (hazard ratio [HR] in stratified log-rank analysis 0·87, 95% CI 0·72-1·07; p=0·18). 3-year IDFS was 82·7% (95% CI 80·5-85·0) with chemotherapy alone and 83·7% (81·4-86·0) with bevacizumab and chemotherapy. After 200 deaths, no difference in overall survival was noted between the groups (HR 0·84, 95% CI 0·64-1·12; p=0·23). Exploratory biomarker assessment suggests that patients with high pre-treatment plasma VEGFR-2 might benefit from the addition of bevacizumab (Cox interaction test p=0·029). Use of bevacizumab versus chemotherapy alone was associated with increased incidences of grade 3 or worse hypertension (154 patients [12%] vs eight patients [1%]), severe cardiac events occurring at any point during the 18-month safety reporting period (19 [1%] vs two [<0·5%]), and treatment discontinuation (bevacizumab, chemotherapy, or both; 256 [20%] vs 30 [2%]); we recorded no increase in fatal adverse events with bevacizumab (four [<0·5%] vs three [<0·5%]). Bevacizumab cannot be recommended as adjuvant treatment in unselected patients with triple-negative breast cancer. Further follow-up is needed to assess the potential effect of bevacizumab on overall survival. F Hoffmann-La Roche.
    The Lancet Oncology 08/2013; · 25.12 Impact Factor
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    ABSTRACT: In patients with hormone receptor-positive advanced breast cancer, response to endocrine therapy is frequently limited by endocrine resistance. One important mechanism of resistance is related to mammalian target of rapamycin (mTOR), a molecule involved in the activation of alternative signaling pathways. Preclinically, resensitization of endocrine resistance can be achieved by the addition of the mTOR inhibitor everolimus to endocrine therapy. Recent results of clinical trials confirmed the clinical activity of combining everolimus and endocrine therapy in neoadjuvant and advanced breast cancer. The BOLERO-2 trial demonstrated significant progression-free survival benefits for the addition of everolimus to exemestane. These data were the basis for the recent approval of everolimus in combination with exemestane for the treatment of advanced hormone r eceptor-positive breast cancer. In clinical practice, the following 3 patient groups are particularly suitable for this treatment: those with progression on aromatase inhibitor therapy, those who respond well to chemotherapy and might benefit from subsequent endocrine therapy, and those with non-aggressive tumor biology. Everolimus treatment requires careful clinical monitoring due to the potentially serious side effects, e.g. stomatitis and pneumonitis. It is also important to educate patients and physicians in order to increase their awareness of side effects. At present, everolimus is investigated in clinical trials.
    Breast Care 08/2013; 8(4):293-299. · 0.68 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 advance online publication, 18 July 2013; doi:10.1038/bjc.2013.367 www.bjcancer.com.
    British Journal of Cancer 07/2013; · 5.08 Impact Factor

Publication Stats

6k Citations
1,399.34 Total Impact Points

Institutions

  • 1989–2014
    • Medical University of Vienna
      • • Comprehensive Cancer Center Vienna
      • • Institut für Medizinische Psychologie
      • • Institut für Spezifische Prophylaxe und Tropenmedizin
      • • Klinische Abteilung für Onkologie
      • • Institut für Sozialmedizin
      • • Universitätsklinik für Innere Medizin I
      Wien, Vienna, Austria
  • 2013
    • Alexandra Regional General Hospital
      Athínai, Attica, Greece
    • National Institute of Oncology
      Budapeŝto, Budapest, Hungary
  • 1988–2013
    • Vienna General Hospital
      Wien, Vienna, Austria
  • 2008–2011
    • Medizinische Universität Innsbruck
      • • Univ.-Klinik für Innere Medizin V (Hämatologie und Onkologie)
      • • Department für Frauenheilkunde
      Innsbruck, Tyrol, Austria
    • Wiener Krankenanstaltenverbund
      • 3rd Department of Medicine
      Wien, Vienna, Austria
    • Paracelsus Medical University Salzburg
      • Laboratory for Immunological and Molecular Cancer Research
      Salzburg, Salzburg, Austria
  • 2010
    • University of Hamburg
      • Department of Gynaecology
      Hamburg, Hamburg, Germany
    • Democritus University of Thrace
      • Department of Internal Medicine I
      Komotiní, Anatoliki Makedonia kai Thraki, Greece
  • 1987–2006
    • University of Vienna
      • • Clinic for Internal Medicine I
      • • Department of Surgery
      • • Department of Internal Medicine III
      Wien, Vienna, Austria
  • 2005
    • Landeskrankenhaus Graz
      Gratz, Styria, Austria