Multivariable regression analysis of febrile neutropenia occurrence in early breast cancer patients receiving chemotherapy assessing patient-related, chemotherapy-related and genetic risk factors

Pfeil, Alena M.; Vulsteke, Christof; Paridaens, Robert; Dieudonné, Anne-Sophie; Pettengell, Ruth; Hatse, Sigrid; Neven, Patrick; Lambrechts, Diether; Szucs, Thomas D.; Schwenkglenks, Matthias; Wildiers, Hans

doi:10.1186/1471-2407-14-201

Cited by 23 publications

(20 citation statements)

References 34 publications

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“…suggested a direct association of risk factors with FN, the authors evaluated the predictive value of patient‐related, chemotherapy‐related and genetic risk factors for FN in breast cancer patients. Their multivariate regression identified that lower platelet count and hemoglobin at baseline and higher ALT were significantly associated with higher occurrence of FN . Also, in a study by Tang et al ., low baseline platelet count was a risk factor for grade 4 neutropenia in breast cancer patients .…”

Section: Discussionmentioning

confidence: 91%

Risk factors for neutropenia and febrile neutropenia following prophylactic pegfilgrastim

Lee

Yee

Kim

et al. 2019

Asia-Pac J Clncl Oncology

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Aim: Neutropenia is a common side effect of myelosuppressive chemotherapy. Administration of granulocyte colony-stimulating factor is being used for neutropenia prophylaxis, but there are patients who develop neutropenia or febrile neutropenia despite prophylaxis. We attempted to identify potential risk factors for chemotherapy-induced neutropenia in patients with pegfilgrastim prophylaxis. Methods:This was a single-center, retrospective, observational study of patients with breast cancer or diffuse large B-cell lymphoma. We obtained patients' data from electronic medical records, including baseline demographics and clinical characteristics regarding diseases, treatments and laboratory values. The outcome measures assessed were the incidence of neutropenia and febrile neutropenia.Results: There were a total of 127 patients, including 77 patients with diffuse large B-cell lymphoma (DLBCL) and 50 patients with breast cancer, and we analyzed 722 chemotherapy cycles.We found 88 cases (12.2%) of grade 3 or 4 neutropenia and 39 cases of febrile neutropenia (5.4%).In the univariate analysis, variables associated with both grade 3 or 4 neutropenia and febrile neutropenia were age, cancer type, cancer stage, radiotherapy and platelet count. A multivariate logistic regression model revealed that age, radiotherapy and platelet count were significant factors in severe neutropenia, whereas platelet count was the only statistically significant factor in febrile neutropenia. Platelet counts of less than 150 000/mm 3 increased the risk of neutropenia and febrile neutropenia approximately fourfold. In the subgroup analysis of patients with DLBCL, it was found that platelet count was a significant factor for both neutropenia and febrile neutropenia. Conclusion:Among cancer patients with pegfilgrastim prophylaxis, advanced age, absence of radiation therapy and low platelet count were independent predictors of neutropenia, and low platelet count was the predictor of febrile neutropenia. K E Y W O R D Sbreast neoplasm, chemotherapy-induced febrile neutropenia, diffuse large B-cell lymphoma, filgrastim, neutropenia, risk factors

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Section: Discussionmentioning

confidence: 91%

Risk factors for neutropenia and febrile neutropenia following prophylactic pegfilgrastim

Lee

Yee

Kim

et al. 2019

Asia-Pac J Clncl Oncology

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“…For the patients with germline DNA available (n = 786), a large panel of SNPs (n = 59) related to FEC metabolism was genotyped in 2011 (Sequenom MassARRAY, Sequenom Inc., CA), as also other genetic studies (focusing on general toxicity and survival) were performed on the database [9,[22][23][24]. We now conducted a Pubmed search (May 2014; keywords: single nucleotide polymorphisms and cardiotoxicity) to identify published associations between SNPs and ACT.…”

Section: Snp Selection and Genotypingmentioning

confidence: 99%

Clinical and genetic risk factors for epirubicin-induced cardiac toxicity in early breast cancer patients

Vulsteke

Pfeil

Maggen

et al. 2015

Breast Cancer Res Treat

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Anthracycline-induced cardiotoxicity (ACT) is a well-known serious adverse drug reaction leading to substantial morbidity. The purpose of this study was to assess ACT occurrence and clinical and genetic risk factors in early breast cancer patients. In 6 genes of interest (ABCC1, ABCC2, CYBA, NCF4, RAC2, SLC28A3), 10 single nucleotide polymorphisms (SNPs) involved in ACT were selected based on a literature search. Eight hundred and seventy-seven patients treated between 2000 and 2010 with 3-6 cycles of (neo) adjuvant 5-fluorouracil, epirubicin and cyclophosphamide (FEC) were genotyped for these SNPs using Sequenom MassARRAY. Main outcome measures were asymptomatic decrease of left ventricular ejection fraction (LVEF) > 10 % and cardiac failure grade 3-5 (CTCAE 4.0). To evaluate the impact of these 10 SNPs as well as clinical factors (age, relative dose intensity of epirubicin, left-sided radiotherapy, occurrence of febrile neutropenia, and planned and received cycles of epirubicin) on decrease of LVEF and cardiac failure, we performed uni- and multivariable logistic regression analysis. Additionally, exploratory analyses including 11 additional SNPs related to the metabolism of anthracyclines were performed. After a median follow-up of 3.62 years (range 0.40-9.60), a LVEF decline of > 10 % occurred in 153 patients (17.5 %) and cardiac failure in 16 patients (1.8 %). In multivariable analysis, six cycles of FEC compared to three cycles received and heterozygous carriers of the rs246221 T-allele in ABCC1 relative to homozygous carriers of the T-allele were significantly associated with LVEF decline of > 10 % (OR 1.3, 95 % CI 1.1-1.4, p < 0.001 and OR 1.6, 95 % CI 1.1-2.3, p = 0.02). Radiotherapy for left-sided breast cancer was associated with cardiac failure (OR 3.7, 95 % CI 1.2-11.5, p 0.026). The other 9 SNPs and clinical factors tested were not significantly associated. In our exploratory analysis, no other SNPs related to anthracycline metabolism were retained in the multivariate model for prediction of LVEF decline. ACT in breast cancer patients is related to number of received cycles of epirubicin and left-sided radiotherapy. Additional studies should be performed to independently confirm the potential association between rs246221 in ABCC1 and LVEF.

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“…Research studies have been published that investigate genetic risk factors for chemotherapy-induced NLEs in patients with breast cancer [ 26 – 29 ] and other types of tumor [ 30 – 32 ]. Most of the studies concerned have been retrospective candidate gene studies.…”

Section: Introductionmentioning

confidence: 99%

“…Most of the studies concerned have been retrospective candidate gene studies. The largest of them investigated FEC chemotherapy in approximately 1000 breast cancer patients and concluded that adding single nucleotide polymorphisms (SNPs) to clinical models for predicting FN might be able to improve the prediction of such events [ 28 , 29 ]. One smaller study performed a genome-wide association study (GWAS) in 270 Asian patients with different types of solid tumor histology [ 32 ] and found that SNPs in MCPH1 were predictive for chemotherapy-induced neutropenia or leukopenia.…”

Section: Introductionmentioning

confidence: 99%

Clinical validation of genetic variants associated with in vitro chemotherapy-related lymphoblastoid cell toxicity

et al. 2017

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Hematotoxicity is one of the major side effects of chemotherapy. The aim of this study was to examine the association between single nucleotide polymorphisms (SNPs) and hematotoxicity in breast cancer patients in a subset of patients of the SUCCESS prospective phase III chemotherapy study. All patients (n = 1678) received three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by three cycles of docetaxel or docetaxel/gemcitabine, depending on randomization. Germline DNA was genotyped for 246 SNPs selected from a previous genome-wide association study (GWAS) in a panel of lymphoblastoid cell lines, with gemcitabine toxicity as the phenotype. All SNPs were tested for their value in predicting grade 3 or 4 neutropenic or leukopenic events (NLEs). Their prognostic value in relation to overall survival and disease-free survival was also tested.None of the SNPs was found to be predictive for NLEs during treatment with docetaxel/gemcitabine. Two SNPs in and close to the PIGB gene significantly improved the prediction of NLEs after FEC, in addition to the factors of age and body surface area. The top SNP (rs12050587) had an odds ratio of 1.38 per minor allele (95% confidence interval, 1.17 to 1.62). No associations were identified for predicting disease-free or overall survival.Genetic variance in the PIGB gene may play a role in determining interindividual differences in relation to hematotoxicity after FEC chemotherapy.

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Multivariable regression analysis of febrile neutropenia occurrence in early breast cancer patients receiving chemotherapy assessing patient-related, chemotherapy-related and genetic risk factors

Cited by 23 publications

References 34 publications

Risk factors for neutropenia and febrile neutropenia following prophylactic pegfilgrastim

Risk factors for neutropenia and febrile neutropenia following prophylactic pegfilgrastim

Clinical and genetic risk factors for epirubicin-induced cardiac toxicity in early breast cancer patients

Clinical validation of genetic variants associated with in vitro chemotherapy-related lymphoblastoid cell toxicity

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