Austrian treatment algorithms in HER2-positive metastatic breast cancer: a 2022 update.

In the past 12 months a plethora of relevant novel data for the treatment of metastatic HER2 positive breast cancer were published. To bring this new evidence into a clinical perspective, a group of Austrian breast cancer specialists updated their previously published treatment algorithm for those patients. For this consensus paper a total of eight scenarios were developed in which treatment strategies appropriate for specific patient profiles were evaluated. Consensus was established by detailed discussions of each scenario and by reaching full consensus.

Austrian recommendations for the management of essential thrombocythemia.

According to the World Health Organization (WHO) classification, essential (primary) thrombocythemia (ET) is one of several Bcr-Abl negative chronic myeloproliferative neoplasms (MPN). The classical term MPN covers the subcategories of MPN: ET, polycythemia vera (PV), primary myelofibrosis (PMF), and prefibrotic PMF (pPMF). ET is marked by clonal proliferation of hematopoietic stem cells, leading to a chronic overproduction of platelets. At the molecular level a JAK2 (Janus Kinase 2), calreticulin, or MPL mutation is found in the majority of patients. Typical ongoing complications of the disease include thrombosis and hemorrhage. Primary and secondary prevention of these complications can be achieved with platelet function inhibitors and various cytoreductive drugs including anagrelide, hydroxyurea and interferon. After a long follow up, in a minority of ET patients the disease transforms into post-ET myelofibrosis or secondary leukemia. Overall, life expectancy with ET is only slightly decreased.

Correction to: Ruxolitinib therapy formyelofibrosis in Austria : Consensus on therapy management.

Correction to:Wien Klin Wochenschr 2018 https://doi.org/10.1007/s00508-018-1365-5 The original version of this article unfortunately contained a mistake. Table Nr. 1 was inconsistent. The corrected version of Table 1 is given below. We apologize for any inconveniences this may have ….

Austrian recommendations for the management of polycythemia vera.

Polycythemia vera (PV) is a clonal disease arising from hematopoietic stem cells. Erythrocytosis is the hallmark of the disease but leukocytosis, thrombocytosis and splenomegaly may also be present. Thromboembolic complications occur in about 20% of patients. Circulatory disturbances as well as pruritus represent frequent symptoms of the disease. Mutations in the JAK2 gene are present in 95% of patients in exon 14 (V617F) and in 3% in exon 12. The main goal of the treatment for patients with PV is the prevention of thromboembolic events, transformation to myelofibrosis and acute myeloid leukemia. Interferon alpha and hydroxyurea are used as first-line treatment for high risk patients. For patients unresponsive to first-line therapy ruxolitinib is available.

Ruxolitinib therapy for myelofibrosis in Austria : Consensus on therapy management.

The oral Janus associated kinase (JAK1/2) inhibitor ruxolitinib has been available for treatment of patients with intermediate or high-risk myelofibrosis in Europe since 2012. Since its introduction, the expertise of prescribing doctors with respect to ruxolitinib function, efficacy and adverse effects has consistently been augmented, resulting in therapy modalities that are better tailored to individual patients as well as in increased safety of the treatment. The present consensus on ruxolitinib therapy management has been elaborated by Austrian experts in myeloproliferative neoplasms in line with international treatment guidelines. Our recommendations aim to contribute to an improved management of patients with myelofibrosis treated with ruxolitinib.

Association between subjective risk perception and objective risk estimation in patients with atrial fibrillation: a cross-sectional study.

OBJECTIVE: Oral anticoagulation (OAC) is state-of-the-art therapy for atrial fibrillation (AF), the most common arrhythmia worldwide. However, little is known about the perception of patients with AF and how it correlates with risk scores used by their physicians. Therefore, we correlated patients' estimates of their own stroke and bleeding risk with the objectively predicted individual risk using CHA2DS2-VASc and HAS-BLED scores. DESIGN: Cross-sectional prevalence study using convenience sampling and telephone follow-up. SETTINGS: Eight hospital departments and one general practitioner in Austria. Patients' perception of stroke and bleeding risk was opposed to commonly used risk scoring. PARTICIPANTS: Patients with newly diagnosed AF and indication for anticoagulation. MAIN OUTCOME MEASURES: Comparison of subjective risk perception with CHA2DS2-VASc and HAS-BLED scores showing possible discrepancies between subjective and objective risk estimation. Patients' judgement of their own knowledge on AF and education were also correlated with accuracy of subjective risk appraisal. RESULTS: Ninety-one patients (age 73±11 years, 45% female) were included in this study. Subjective stroke and bleeding risk estimation did not correlate with risk scores (ρ=0.08 and ρ=0.17). The majority of patients (57%) underestimated the individual stroke risk. Patients feared stroke more than bleeding (67% vs 10%). There was no relationship between accurate perception of stroke and bleeding risks and education level. However, we found a correlation between the patients' judgement of their own knowledge of AF and correct assessment of individual stroke risk (ρ=0.24, p=0.02). During follow-up, patients experienced the following events: death (n=5), stroke (n=2), bleeding (n=1). OAC discontinuation rate despite indication was 3%. CONCLUSIONS: In this cross-sectional analysis of OAC-naive patients with AF, we found major differences between patients' perceptions and physicians' assessments of risks and benefits of OAC. To ensure shared decision-making and informed consent, more attention should be given to evidence-based and useful communication strategies. TRIAL REGISTRATION NUMBER: NCT03061123.

Clinical Outcomes of 217 Patients with Acute Erythroleukemia According to Treatment Type and Line: A Retrospective Multinational Study.

Acute erythroleukemia (AEL) is a rare disease typically associated with a poor prognosis. The median survival ranges between 3-9 months from initial diagnosis. Hypomethylating agents (HMAs) have been shown to prolong survival in patients with myelodysplastic syndromes (MDS) and AML, but there is limited data of their efficacy in AEL. We collected data from 210 AEL patients treated at 28 international sites. Overall survival (OS) and PFS were estimated using the Kaplan-Meier method and the log-rank test was used for subgroup comparisons. Survival between treatment groups was compared using the Cox proportional hazards regression model. Eighty-eight patients were treated with HMAs, 44 front line, and 122 with intensive chemotherapy (ICT). ICT led to a higher overall response rate (complete or partial) compared to first-line HMA (72% vs. 46.2%, respectively; p ≤ 0.001), but similar progression-free survival (8.0 vs. 9.4 months; p = 0.342). Overall survival was similar for ICT vs. HMAs (10.5 vs. 13.7 months; p = 0.564), but patients with high-risk cytogenetics treated with HMA first-line lived longer (7.5 for ICT vs. 13.3 months; p = 0.039). Our results support the therapeutic value of HMA in AEL.

Austrian recommendations for the management of primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis: an expert statement.

The entity "myelofibrosis" represents a subgroup of the Philadelphia chromosome-negative myeloproliferative neoplasms. It comprises primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. This heterogeneous disease is characterized by clonal myeloproliferation, dysregulated kinase signalling and the abnormal expression of several proinflammatory cytokines. Clinically, patients present with symptoms related to thrombocytosis/leukocytosis, anemia and/or progressive splenomegaly. Mutations in Janus kinase 2, an enzyme that is essential for the normal development of erythrocytes, granulocytes, and platelets, notably the V617F mutation, have been identified in approximately 60% of patients with primary myelofibrosis. Recent molecular advances have not only elucidated critical pathways in the pathogenesis of the disease, but also contributed to a more precise assessment of a patient's individual risk. While allogeneic stem cell transplantation remains the only curative treatment, the natural course of the disease and the patient's survival and quality of life may be improved by new treatments, notably ruxolitinib, the first Janus kinase 1/2 inhibitor approved for the management of myelofibrosis. Additional treatment options are being explored.

LOOKING BACK ON 5 YEARS OF HORIZON SCANNING IN ONCOLOGY.

OBJECTIVES: The regularly structured adaptation of health technology assessment (HTA) programs is of utmost importance to sustain the relevance of the products for stakeholders and to justify investment of scarce financial resources. This study describes internal adjustments and external measures taken to ensure the Horizon Scanning Programme in Oncology (HSO) is current. METHODS: Formal evaluation methods comprising a survey, a download, an environmental analysis, and a Web site questionnaire were used to evaluate user satisfaction. RESULTS: The evaluation showed that users were satisfied with HSO outputs in terms of timeliness, topics selected, and depth of information provided. Discussion of these findings with an expert panel led to changes such as an improved dissemination strategy and the introduction of an additional output, that is, the publication of a league table of emerging oncology drugs. The rather high level of international usage and the environmental analysis highlighted a considerable overlap in topics assessed and, thus, the potential for international collaboration. As a consequence, thirteen reports were jointly published based on eleven "calls for collaboration." To further facilitate collaboration and the usability of reports for other agencies, HSO reports will be adjusted according to tools developed at a European level. CONCLUSIONS: Evaluation of the impact of HTA programs allows the tailoring of outputs to fit the needs of the target population. However, within a fast developing HTA community, estimates of impact will increasingly be determined by international collaborative efforts. Refined methods and a broader definition of impact are needed to ultimately capture the efficiency of national HTA programs.

Association of vascular endothelial growth factor--a gene polymorphisms and haplotypes with breast cancer metastases.

BACKGROUND: Vascular endothelial growth factor (VEGF-A) is a key regulator of tumor-induced angiogenesis and essential for tumor growth and distant tumor spread. The aim of the present study was to evaluate the role of VEGF-A polymorphisms and haplotypes for metastatic progression in breast cancer patients. MATERIAL AND METHODS: We performed a prospective study including 801 breast cancer patients. Occurrence of metastases was examined in regular follow-up investigations. Seven VEGF-A polymorphisms were selected and determined by 5'-nuclease assays (TaqMan). The selection of VEGF-A variants was based upon their location (promoter or UTR) as well as a minor allele frequency of at least 0.10. Haplotypes and linkage disequilibrium were determined using the Haploview program. RESULTS: Within a median follow-up time of 84 months, 165 (21%) patients developed distant metastases. In univariate analysis, carriers of the CCCCC haplotype formed by five polymorphisms upstream the coding region were at decreased risk of distant metastases [hazard ratio (HR)=0.743; 95% CI 0.579-0.953; p=0.019]. Univariate analysis also revealed a decreased risk of distant metastases for postmenopausal patients carrying the -634G>C polymorphism (HR 0.704; 95% CI 0.514-0.965; p=0.029) and the CCCCC haplotype (HR=0.645; 95% CI 0.464-0.898; p=0.009). After adjustment for other co-variates, the HR for distant metastases was 0.651 (95% CI 0.447-0.948) for postmenopausal carriers of the -634G>C polymorphism (p=0.025; corrected p-value=0.262), and 0.586 (95% CI 0.393-0.873) for postmenopausal patients with the CCCCC haplotype (p=0.009, corrected p-value=0.189). CONCLUSION: The results from univariate and multivariate analyses suggest an influence of VEGF-A gene variants on the development of distant metastases in breast cancer patients. However, none of the observed associations reached statistical significance after correction for the effects of multiple testing. Additional prospective and sufficiently powered studies are essential before firm conclusions about the role of VEGF-A gene variants for distant progression in breast cancer can be drawn.

Azacitidine in 302 patients with WHO-defined acute myeloid leukemia: results from the Austrian Azacitidine Registry of the AGMT-Study Group.

Data on efficacy and safety of azacitidine in acute myeloid leukemia (AML) with >30 % bone marrow (BM) blasts are limited, and the drug can only be used off-label in these patients. We previously reported on the efficacy and safety of azacitidine in 155 AML patients treated within the Austrian Azacitidine Registry (clinicaltrials.gov identifier NCT01595295). We herein update this report with a population almost twice as large (n = 302). This cohort included 172 patients with >30 % BM blasts; 93 % would have been excluded from the pivotal AZA-001 trial (which led to European Medicines Agency (EMA) approval of azacitidine for high-risk myelodysplastic syndromes (MDS) and AML with 20-30 % BM blasts). Despite this much more unfavorable profile, results are encouraging: overall response rate was 48 % in the total cohort and 72 % in patients evaluable according to MDS-IWG-2006 response criteria, respectively. Median OS was 9.6 (95 % CI 8.53-10.7) months. A clinically relevant OS benefit was observed with any form of disease stabilization (marrow stable disease (8.1 months), hematologic improvement (HI) (9.7 months), or the combination thereof (18.9 months)), as compared to patients without response and/or without disease stabilization (3.2 months). Age, white blood cell count, and BM blast count at start of therapy did not influence OS. The baseline factors LDH >225 U/l, ECOG ≥2, comorbidities ≥3, monosomal karyotype, and prior disease-modifying drugs, as well as the response-related factors hematologic improvement and further deepening of response after first response, were significant independent predictors of OS in multivariate analysis. Azacitidine seems effective in WHO-AML, including patients with >30 % BM blasts (currently off-label use). Although currently not regarded as standard form of response assessment in AML, disease stabilization and/or HI should be considered sufficient response to continue treatment with azacitidine.

Azacitidine in patients with WHO-defined AML - results of 155 patients from the Austrian Azacitidine Registry of the AGMT-Study Group.

OBJECTIVE: The Austrian Azacitidine Registry is a multi-center database (ClinicalTrials.gov: NCT01595295). The nature and intent of the registry was to gain a comprehensive view of the use, safety and efficacy of the drug in a broad range of AML-patients treated in real-life scenarios. PATIENTS AND METHODS: The sole inclusion criteria were the diagnosis of WHO-AML and treatment with at least one dose of azacitidine. No formal exclusion criteria existed. A total of 155 AML-patients who were mostly unfit/ineligible for intensive chemotherapy, or had progressed despite conventional treatment, were included. True ITT-analyses and exploratory analyses regarding the potential prognostic value of baseline-variables/performance-/comorbidity-/risk-scores on overall survival (OS), were performed. RESULTS: In this cohort of 155 pretreated (60%), and/or comorbid (87%), elderly (45% ≥75 years) AML-patients, azacitidine was well tolerated and efficacious, with an overall response rate (CR, mCR, PR, HI) of 45% in the total cohort (ITT) and 65% in patients evaluable according to IWG-criteria, respectively. Pre-treatment with conventional chemotherapy (P = .113), age ≤/>80 years (P = .853), number of comorbidities (P = .476), and bone marrow (BM) blast count (P = .663) did not influence OS. In multivariate analysis hematologic improvement alone (without the requirement of concomitant bone marrow blast reduction), although currently not regarded as a standard form of response assessment in AML, was sufficient to confer OS benefit (18.9 vs. 6.0 months; P = .0015). Further deepening of response after first response was associated with improved OS (24.7 vs. 13.7 months; P < .001). CONCLUSIONS: In this large cohort of AML-patients treated with azacitidine, age >80 years, number of comorbidities and/or BM-blasts >30% did not adversely impact OS.

[Primary immune thrombocytopenia in adults: diagnostics and treatment consensus statement of the Austrian Society of Hematology and Oncology (ÖGHO)]. / Primäre Immunthrombozytopenie des Erwachsenen - Diagnostik und Therapie, Konsensus-Statement der Österreichischen Gesellschaft für Hämatologie und Onkologie (ÖGHO).

Immune Thrombocytopenia (ITP) is a rare and - in most patients - mild disease, but might be associated with severe or even life-threatening bleeding complications. The treatment of ITP has partly changed in recent years, due to new therapeutic options. International guidelines changed accordingly. This consensus statement by the Austrian Society of Hematology and Oncology (OEGHO) is not a new evaluation of the current evidence, but rather tries to discuss the available international guidelines and adapt them to the situation in Austria. The subject is primary ITP in adults only. Classification, epidemiology, clinical presentation and diagnostics of ITP, and especially the management of this disease, are discussed in detail. This includes current aspects of first, second, and third line therapies, splenectomy with its indications and contraindications, and the use of new therapeutic options like thrombopoetin receptor agonists (TRA).

Impact of UGT2B7 His268Tyr polymorphism on the outcome of adjuvant epirubicin treatment in breast cancer.

INTRODUCTION: Epirubicin is a common adjuvant treatment for breast cancer. It is mainly eliminated after glucuronidation through uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7). The present study aimed to describe the impact of the UGT2B7(His268Tyr) polymorphism on invasive disease-free survival in breast cancer patients after epirubicin treatment. METHODS: This is a pharmacogenetic study based on samples collected from 745 breast cancer patients of the Austrian Tumor of breast tissue: Incidence, Genetics, and Environmental Risk factors (TIGER) cohort who did not present metastases at baseline. This cohort included 205 women with epirubicin-based combination chemotherapy, 113 patients having received chemotherapy without epirubicin and 427 patients having received no chemotherapy at all. Of the epirubicin-treated subgroup, 120 were subsequently treated with tamoxifen. For all women UGT2B7(His268Tyr) was genotyped. Invasive disease-free survival was assessed using Kaplan-Meier and Cox's proportional hazard regression analysis. RESULTS: Among the 205 epirubicin-treated patients, carriers of two UGT2B7(268Tyr) alleles had a mean invasive disease-free survival of 8.6 (95% confidence interval (CI) 7.9 to 9.3) years as compared to 7.5 (95% CI 6.9 to 8.0) years in carriers of at least one UGT2B7(268His) allele (adjusted hazard ratio (HR) = 2.64 (95% CI 1.22 to 5.71); P = 0.014). In addition, the impact of the UGT2B7(His268Tyr) polymorphism became even more pronounced in patients subsequently treated with tamoxifen (adjusted HR = 5.22 (95% CI 1.67 to 26.04); P = 0.015) whereas no such difference in invasive disease-free survival was observed in patients not receiving epirubicin. CONCLUSIONS: Breast cancer patients carrying the UGT2B7(268Tyr/Tyr) genotype may benefit most from adjuvant epirubicin-based chemotherapy. These results warrant confirmation in further studies.

Single nucleotide polymorphisms of integrin alpha-2 and beta-3 genes are not associated with relapse-free and overall survival in colorectal cancer patients.

BACKGROUND: Integrins influence tumourigenesis, tumor progression and development of metastases. The impact of polymorphisms in integrin genes on relapse-free survival (RFS) and overall survival (OS) for 433 Caucasian patients with colorectal cancer was analysed in this retrospective study. PATIENTS AND METHODS: A Cox regression model including integrin genotype, age, grading, tumour size, number of lymph nodes examined, number of metastatic lymph nodes, stage and application of fluorouracil-based adjuvant chemotherapy was used to estimate their effect. RESULTS: After a median follow-up of 41 months for RFS and 55 months for OS, no significant correlation between the ITGA2 1648A allele (RFS p=0.618, OS p=0.604), the ITGA2 807T allele (RFS p=0.603, OS p=0.807) and the ITGB3 176C allele (RFS p=0.719, OS p=0.261) and survival was detectable. CONCLUSION: The investigated integrin polymorphisms are not associated with RFS or OS in colorectal cancer patients.

Impact of CYP2D6*4 genotype on progression free survival in tamoxifen breast cancer treatment.

OBJECTIVE: The cytochrome P450 2D6 (CYP2D6) polymorphism was reported to have a significant impact on outcome of tamoxifen treatment in estrogen receptor positive breast cancer patients. The objective of this study was to explore the effect of the CYP2D6*4 polymorphism on tamoxifen treatment outcome in a cohort of patients from a single clinical trial which included women with a history of previous chemotherapy. RESEARCH DESIGN AND METHODS: A total of 493 patients of the Austrian TIGER study receiving adjuvant tamoxifen therapy were studied for this pharmacogenetic interaction. All women with estrogen receptor positive tumors and tamoxifen therapy longer than 6 months were genotyped for CYP2D6*4 using TaqMan technology. Time to tumor progression, defined as local, regional, distant recurrence or contralateral breast cancer and progression free survival, was analyzed. RESULTS: No significant difference in time to tumor progression or progression free survival between the CYP2D6*4 genotype groups in the overall study cohort was found. In a subgroup of patients treated with chemotherapy the CYP2D6*4 poor metabolizers had a tendency towards a shorter mean time to progression. In this group the mean time to tumor progression and the progression free survival were 1.0 years in the CYP2D6*4/*4 group, 6.3 years in the *1/*4 group and 4.97 years in the *1/*1 group (Wilcoxon p = 0.104). CONCLUSION: While earlier data on CYP2D6 and tamoxifen excluded women with prior chemotherapy, the present analysis suggests that CYP2D6*4 genotype might be particularly crucial in this group of high-risk patients. Key limitations are restriction to the CYP2D6*4 allele and missing data of comedication.

Association of hypoxia-inducible factor 1-alpha gene polymorphisms and colorectal cancer prognosis.

BACKGROUND: Hypoxia inducible factor-1 (HIF-1) is the key regulator of cellular responses to hypoxia and plays a central role in tumour growth. Recently, two single nucleotide polymorphisms (SNPs) in the HIF-1 alpha gene, C1772T and G1790A, were shown to cause significantly higher transcriptional activity than did the wild-type. This study aimed to investigate the effect of these SNPs on the prognosis of colorectal cancer (CRC). PATIENTS AND METHODS: DNA from 336 CRC patients was genotyped. Genotypes of each polymorphism were tested for association with disease-free survival (DFS) using univariate and multivariate Cox-regression analysis. RESULTS: Genotype frequencies were: CC 75.6%, CT 18.8% and TT 1.8% for HIF1A1 C1772T and GG 93.2%, GA 2.7% and AA 0% for G1790A. A statistically significant association between DFS and clinicopathological features was observed. However, no association was found between HIF1A1 C1772T (p=0.44; risk ratio of recurrence, RR=1.19, 95% confidence interval, CI=0.77 to 1.83) and G1790A (p=0.89; RR=0.92, 95% CI=0.29 to 2.90) polymorphisms and DFS in univariate and multivariate Cox-regression analysis. CONCLUSION: These results suggest that HIF1A1 C1772T and G1790A polymorphisms are not involved in the progression or metastasis of CRC.

Single nucleotide polymorphisms in the hypoxia-inducible factor-1 gene and colorectal cancer risk.

With an incidence of about 300 000 new cases colorectal cancer (CRC) is the second leading cause of cancer-related death in Europe and the United States. Environmental and genetic factors influence CRC risk. Hypoxia-inducible factor-1 (HIF-1), a heterodimeric protein composed of two subunits, HIF-1 alpha and HIF-1 beta, plays a critical role in oxygen homeostasis and is involved in angiogenesis and cell proliferation. The gene for the HIF-1 alpha subunit (HIF1A) carries two common missense mutations-P582S (rs11549465) and A588T (rs11549467)-which both have been related to increased trans-activation capacity of HIF1A. In our case-control study we investigated the association between these polymorphisms and CRC risk. We investigated 381 patients with histologically confirmed CRC and 2156 control subjects. HIF1A genotypes were determined by exonuclease (TaqMan) assays. For determination of microvessel density (MVD) tumor sections were stained using a mouse monoclonal antibody recognizing the pan-endothelial marker CD31. In a multivariate logistic regression analysis including age and sex neither the HIF1A 582S allele (Odds ratio: 1.204; 95% confidence interval 0.911-1.592; P = 0.193) nor the 588T allele was significantly associated with CRC (Odds ratio: 0.851; 95% confidence interval 0.444-1.631; P = 0.626). However, in an exploratory analysis, the HIF1A 588T allele was associated with tumor localization (P = 0.016) and tumor size (P = 0.003). MVD was similar in tumors of patients carrying HIF1A 588T allele and patients without this rare allele. We conclude that functional polymorphisms in the HIF1A gene do not modify CRC risk but maybe associated with clinic-pathological features of the disease.

Analysis of common germline polymorphisms as prognostic factors in patients with lymph node-positive breast cancer.

PURPOSE: Women with breast cancer that initially involves local lymph nodes have a higher risk for local recurrence or developing metastases. Recent data suggest that germline polymorphism is a significant, previously unrecognized factor in breast cancer progression and metastasis. We assessed the influence of 16 selected common germline polymorphisms in disease-free survival and overall survival among 216 women diagnosed with lymph node-positive breast cancer. RESULTS: The rare allele of FAS 1377G>A was significantly associated with prolonged disease-free survival (P = 0.012, risk ratio of recurrence (RR) = 0.557, 95% confidence interval (CI) = 0.353-0.878) in univariate analysis. After adjusting for known breast cancer prognostic factors the association remained significant (P = 0.050, RR = 0.500, CI = 0.309-0.809). In overall survival analysis we found a significant association of the FAS 1377G>A (P = 0.040, RR = 0.451, CI = 0.496-1.188) and IL10 592C>A polymorphisms (P = 0.020, RR = 1.707, CI = 1.087-2.680) in the univariate Cox regression. The effect remained statistically significant in the multivariate analysis for the IL10 592C>A polymorphism (P = 0.013, RR 1.841, CI 1.140-2.973). No association was found for MTHFR 677C>T, VEGF 936C>T, CCND1 870G>A, TGFB1 29T>C, FASLG 844C>T, FAS 670A>G, GPB3 825C>T, ITGA2 807C>T, ITGA2 1648G>A, ITGB3 176T>C, MMP1 -1607 1G/2G, MMP3 5A/6A, PTGS2 8473T>C, IL10 592C>A and SULT1A1 638G>A polymorphisms and disease-free survival or overall survival. CONCLUSIONS: Our data suggest that the FAS 1377G>A and IL10 592C>A polymorphisms could modify disease-free and overall survival in women with lymph node-positive breast cancer.