Single-nucleotide polymorphisms and the effectiveness of taxane-based chemotherapy in premenopausal breast cancer: a population-based cohort study in Denmark

Hjorth, Cathrine Fonnesbech; Damkier, Per; Stage, Tore Bjerregaard; Feddersen, Søren; Hamilton-Dutoit, Stephen; Rørth, Mikael; Ejlertsen, Bent; Lash, Timothy L.; Ahern, Thomas P.; Sørensen, Henrik Toft; Cronin‐Fenton, Deirdre

doi:10.1007/s10549-022-06596-2

Cited by 3 publications

(1 citation statement)

References 53 publications

(61 reference statements)

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“…GSP1 codes for an enzyme that inactivates toxic substances, and in carriers of rs1138272 (a variant from the meta-analysis) mortality was increased (276). This SNV was included in the C2 model for numbness in feet, but it is unclear whether or how toxicity and efficacy are related, and the variants in CYP3A and SLCO1B1 were, on the contrary, associated with decreased mortality (277). In the further development of polygenic prediction models, the association between risk of toxicity and chance of efficacy would be of interest to evaluate, although challenging (278).…”

Section: Polygenic Prediction Modelsmentioning

confidence: 99%

Taxane-Induced Peripheral Neuropathy among Early-Stage Breast Cancer Survivors : Prevalence, Risk Factors, Quality of Life and Genetic Prediction Models

Engvall

2024

Linköping University Medical Dissertations

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Background: Taxane-induced peripheral neuropathy (TIPN) is a common and distressful side effect. Little is known on how long TIPN persist and its effect on health-related quality of life (HRQL). The overall aim of this thesis was to study the prevalence and severity of persistent TIPN, to investigate its impact on HRQL and to explore the clinical and genetic risk factors for TIPN among early-stage breast cancer survivors (ESBCS).Methods: A population-based cohort of 884 recurrence-free ESBCS diagnosed 2010-2015 in the Southeast Health Care region, Sweden and 1768 control women without prior cancer, who received a postal questionnaire including EORTC chemotherapy-induced peripheral neuropathy (CIPN20) and QLQ-C30 instruments. Prevalence of TIPN symptoms and clinical risk factors were explored. Adjusted relative risks (RR) were estimated for ESBCS compared to control women. For impact on HRQL, adjusted mean scores of QLQ-C30 scales among ESBCS with and without TIPN were calculated. Blood samples from 362 ESBCS were whole-exome sequenced. We leveraged logistic regression models to develop and validate polygenic prediction models to estimate the risk of persistent PN symptoms in a training and test cohort.Results: The response rate was 79% for ESBCS and 59% for controls. The median time post-taxane was 3.6 years. The adjusted RR for ESBCS vs. controls was highest (RR 1.8) for tingling in feet and numbness in feet. Individual sensory symptoms occurred in 9%-48% and motor symptoms in 7%-61% of ESBCS. The most prevalent symptoms were difficulty opening jar and cramps in feet. Paclitaxel, older age, overweight, diabetes mellitus, vibrating hand tools, smoking and autoimmune disease were independent risk factors (Study I). All 13 sensory and motor TIPN symptoms at increased risks among ESBCS had a significant impact on global health status, which worsened with increased severity of TIPN. Between 30%-93% of ESBCS with moderate-severe TIPN reported a clinically important impairment of functioning and personal finances. Moderate-severe difficulty climbing stairs and problems standing/walking were associated with medium-large clinically important differences (Study II). In the explorative sub-study, two of five prediction models based on genetic and clinical risk factors obtained Did you have difficulty hearing?Difficulty hearingPlease answer the following question only if you drive a car Did you have difficulty using the pedals? Difficulty using pedals Docetaxel60+Capecitabin900 2 w x 3-4 Concomitant with EC-T 3w, every 3 weeks; 2w, every 2 weeks; EC, Epirubicin-Cyclophosphamide. Note: As suggested in revision of guidelines.Neoadjuvant chemotherapy is the preferred choice in HER2+ and TNBC due to highly proliferative disease, the possibility to evaluate response (26), and since the evidence as to the efficacy of additional treatments is only shown in trials conducted in a neoadjuvant setting. In HER2+ disease, 'Plus' Increase of sensation Tingling, Burning sensation Allodynia, Hyperalgesia Cramps 'Minus' Loss of function Num...

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Section: Polygenic Prediction Modelsmentioning

confidence: 99%

Taxane-Induced Peripheral Neuropathy among Early-Stage Breast Cancer Survivors : Prevalence, Risk Factors, Quality of Life and Genetic Prediction Models

Engvall

2024

Linköping University Medical Dissertations

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Genetic variants and social benefit receipt in premenopausal women with breast cancer treated with docetaxel: a Danish population-based cohort study

Schmidt,

Hjorth,

Farkas

et al. 2024

Breast Cancer Res Treat

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Purpose Breast cancer patients’ need for social benefits may increase following taxane-based chemotherapy, due to long-lasting side effects. Specific single nucleotide polymorphisms (SNPs) may mediate such side effects. We investigated the association between SNPs related to taxane metabolism, transport, toxicity, or DNA and neural repair, and receipt of social benefits. Methods From the Danish Breast Cancer Group, we identified premenopausal women diagnosed with stage I–III breast cancer during 2007–2011 and treated with docetaxel-based chemotherapy. We genotyped 21 SNPs from archived breast tumors using TaqMan assays. We ascertained social benefit payments from 1 year before to 5 years after diagnosis, using nationwide, administrative registry data. For each week, we categorized women as receiving health-related benefits (including sick leave and disability pension), labor market-related benefits (including unemployment benefits), or as being self-supporting. We computed rate ratios (RRs) of social benefit receipt for variant carriers (heterozygotes plus homozygotes) vs. non-carriers, using negative binominal regression with robust variance estimation. Results Among 2430 women, 12% received health-related benefits before diagnosis, 80% at diagnosis, and ~ 24% 2 to 5 years after diagnosis. Labor market-related benefits were uncommon (3–6%). All RRs were near-null and/or imprecise. Conclusion We found no clinically meaningful impact of the selected SNPs on social benefit receipt among premenopausal breast cancer survivors treated with docetaxel.

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TNFAIP2 as an emerging therapeutic target in cancer therapy and its underlying mechanisms

Fu,

Yuan

2024

Pharmacological Research

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Single-nucleotide polymorphisms and the effectiveness of taxane-based chemotherapy in premenopausal breast cancer: a population-based cohort study in Denmark

Cited by 3 publications

References 53 publications

Taxane-Induced Peripheral Neuropathy among Early-Stage Breast Cancer Survivors : Prevalence, Risk Factors, Quality of Life and Genetic Prediction Models

Taxane-Induced Peripheral Neuropathy among Early-Stage Breast Cancer Survivors : Prevalence, Risk Factors, Quality of Life and Genetic Prediction Models

Genetic variants and social benefit receipt in premenopausal women with breast cancer treated with docetaxel: a Danish population-based cohort study

TNFAIP2 as an emerging therapeutic target in cancer therapy and its underlying mechanisms

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