Role of pharmacogenetics on adjuvant chemotherapy-induced neutropenia in Chinese breast cancer patients

Tang, Nelson L. S.; Liao, Chen Di; Wang, Xianyou; Mo, Frankie; Chan, Vicky; Ng, Ray Kit; Pang, Elizabeth; Suen, Joyce; Woo, Jean; Park, Yeon Hee

doi:10.1007/s00432-012-1345-5

Cited by 27 publications

(20 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is evidence that pharmacogenomics can predict cytarabine‐related toxicity in the AML context . Outside the AML setting, genotypic variation has been associated with the duration of chemotherapy‐induced neutropenia …”

Section: Discussionmentioning

confidence: 99%

Association between prolonged neutropenia and reduced relapse risk in pediatric AML: A report from the children's oncology group

Sung

Aplenc

Alonzo

et al. 2016

Intl Journal of Cancer

View full text Add to dashboard Cite

Objective was to describe the relationship between the number of sterile site infections and duration of neutropenia during the first four cycles of chemotherapy and the risk of recurrence and overall survival. AAML0531 was a Children’s Oncology Group (COG) randomized phase 3 clinical trial that included 1022 children with de novo AML. For this analysis, we focused on non-Down syndrome favorable and standard risk patients who completed at least 4 cycles of chemotherapy without recurrence or withdrawal during protocol therapy. Those receiving hematopoietic stem cell transplantation in first remission were excluded. 569 patients were included; 274 (48.2%) were favorable risk. The median cumulative time with neutropenia between Induction II to completion of Intensification II was 96 (range 54–204) days. Number of sterile site infections did not influence the risk of relapse or overall survival. However, longer duration of neutropenia was associated with a lower risk of relapse (hazard ratio 0.81 per 20 days neutropenia, P=0.007). Longer duration of neutropenia was associated with a reduced risk of relapse for children with favorable and standard risk AML. Toxicity may be influenced by pharmacogenomics suggesting that individualized chemotherapy dosing may be an effective strategy.

show abstract

Section: Discussionmentioning

confidence: 99%

Association between prolonged neutropenia and reduced relapse risk in pediatric AML: A report from the children's oncology group

Sung

Aplenc

Alonzo

et al. 2016

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Baseline platelet count has been shown to differ between cancer patients with mild and severe haematological toxicity [16], and low haemoglobin has been mentioned as possible risk factor for FN [27] and survival [28]. In the model of FN occurrence in any cycle, higher baseline ALT was significantly associated with FN but not baseline bilirubin [9,29].…”

Section: Discussionmentioning

confidence: 99%

“…However, more refined models are necessary to achieve satisfactory performance in independent patient populations that include existing and emerging types of data, including stable genetic factors that are easily measurable, objective, and potentially independent from the inherent viabilities of clinical decision-making. Several studies have assessed the impact of genetic factors on haematological toxicity, but these studies were small in size or limited to only a few candidate genetic factors [14-16]. …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

View full text Add to dashboard Cite

BackgroundFebrile neutropenia (FN) is common in breast cancer patients undergoing chemotherapy. Risk factors for FN have been reported, but risk models that include genetic variability have yet to be described. This study aimed to evaluate the predictive value of patient-related, chemotherapy-related, and genetic risk factors.MethodsData from consecutive breast cancer patients receiving chemotherapy with 4–6 cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) or three cycles of FEC and docetaxel were retrospectively recorded. Multivariable logistic regression was carried out to assess risk of FN during FEC chemotherapy cycles.ResultsOverall, 166 (16.7%) out of 994 patients developed FN. Significant risk factors for FN in any cycle and the first cycle were lower platelet count (OR = 0.78 [0.65; 0.93]) and haemoglobin (OR = 0.81 [0.67; 0.98]) and homozygous carriers of the rs4148350 variant T-allele (OR = 6.7 [1.04; 43.17]) in MRP1. Other significant factors for FN in any cycle were higher alanine aminotransferase (OR = 1.02 [1.01; 1.03]), carriers of the rs246221 variant C-allele (OR = 2.0 [1.03; 3.86]) in MRP1 and the rs351855 variant C-allele (OR = 2.48 [1.13; 5.44]) in FGFR4. Lower height (OR = 0.62 [0.41; 0.92]) increased risk of FN in the first cycle.ConclusionsBoth established clinical risk factors and genetic factors predicted FN in breast cancer patients. Prediction was improved by adding genetic information but overall remained limited. Internal validity was satisfactory. Further independent validation is required to confirm these findings.

show abstract

“…It includes neutropenia, leukopenia, anaemia or thrombocytopenia. Myelosuppression increases the risk of infection, septicaemia and could even result in death of patients . Docetaxel is used in standard treatments of various types of solid tumours, such as breast, ovarian, prostate, gastric, non‐small‐cell lung, head and neck cancers .…”

Section: What Is Known and Objectivementioning

confidence: 99%

Genetic associations of docetaxel‐based chemotherapy‐induced myelosuppression in Chinese Han population

et al. 2019

View full text Add to dashboard Cite

What is known and objective Myelosuppression, an adverse drug reaction (ADR), often causes medical treatment termination in cancer patients. It has been known that genetic components, such as single‐nucleotide polymorphisms (SNPs), influence the risk of myelosuppression at the individual‐patient level. However, due to ethnic variation in frequency of genetic polymorphisms, results reported in Caucasian patients may not be generalizable to the Chinese Han population. Until now, few researches on myelosuppression included Chinese Han patients. In this study, we conducted a systematic study of potential biomarkers for docetaxel‐induced myelosuppression in Han Chinese patients. Methods We examined 61 SNPs in 36 genes that code for drug transporters, metabolism enzymes, nuclear receptors and DNA repair pathway in 110 Chinese Han patients receiving docetaxel‐based chemotherapy. Genotyping was conducted using the Sequenom MassARRAY system. Significant SNPs were identified by logistic regression, and gene‐gene interactions were investigated by generalized multifactor dimensionality reduction (GMDR) analysis. Results and discussion Our results revealed that 11 SNPs in nine genes (SLC15A1, SLCO1A2, CYP2D6, FMO3, UGT1A1, NAT2, SULT2A1, PXR and HNF4α) were associated with docetaxel‐induced myelosuppression. GMDR analyses suggested that a 3‐locus model: SLC15A1 rs2297322—PXR rs3732359—FMO3 rs2266782 was an appropriate predictive model of docetaxel‐induced myelosuppression (P = .017, Testing Bal.Acc = 0.653, CV Consistency = 10/10). What is new and conclusion Our findings suggest multiple novel predictive biomarkers of docetaxel‐induced myelosuppression: SLC15A1 rs2297322, PXR rs3732359 and FMO3 rs2266782. These discoveries should help in advancing future personalized therapy of docetaxel‐based chemotherapy specific to Chinese Han patients.

show abstract

Role of pharmacogenetics on adjuvant chemotherapy-induced neutropenia in Chinese breast cancer patients

Cited by 27 publications

References 34 publications

Association between prolonged neutropenia and reduced relapse risk in pediatric AML: A report from the children's oncology group

Association between prolonged neutropenia and reduced relapse risk in pediatric AML: A report from the children's oncology group

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

Genetic associations of docetaxel‐based chemotherapy‐induced myelosuppression in Chinese Han population

Contact Info

Product

Resources

About