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Taxane-Induced Peripheral Neuropathy among Early-Stage Breast Cancer Survivors: Prevalence, Risk Factors, Quality of Life and Genetic Prediction Models
Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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 AUC results above 60% in the test cohort. Using the model for numbness in feet (35 SNVs) in the test cohort, 73% survivors were correctly predicted. For tingling in feet (55 SNVs) 70% were correctly predicted (Study III).

Conclusions: Most sensory and motor symptoms are more common among taxane-treated ESBC survivors than in women from the general population, many symptoms persist ≥3.6 years. Persistent TIPN symptoms are associated with clinically relevant impairment of HRQL. Polygenic prediction models including clinical risk factors may be used to estimate the risk of persistent taxane-induced numbness in feet and tingling in feet. 

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2024. , p. 126
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1895
Keywords [en]
Early-stage breast cancer, Taxane, Chemotherapy-induced peripheral neuropathy, Risk factors, Polygenic prediction models
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
URN: urn:nbn:se:liu:diva-201635DOI: 10.3384/9789180755146ISBN: 9789180755139 (print)ISBN: 9789180755146 (electronic)OAI: oai:DiVA.org:liu-201635DiVA, id: diva2:1844886
Public defence
2024-04-19, Originalet, Qulturumhuset, Hus B4, Länssjukhuset Ryhov, Jönköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2024-03-15 Created: 2024-03-15 Last updated: 2024-03-15Bibliographically approved
List of papers
1. Persistent neuropathy among early-stage breast cancer survivors in a population-based cohort
Open this publication in new window or tab >>Persistent neuropathy among early-stage breast cancer survivors in a population-based cohort
2021 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 125, no 3, p. 445-457Article in journal (Refereed) Published
Abstract [en]

Background The prevalence of persistent peripheral neuropathy (PN) in early-stage breast cancer (ESBC) survivors is largely unknown. We explored the occurrence and risk factors of PN among long-term ESBC survivors treated with taxane chemotherapy. Methods A population-based cohort of 884 recurrence-free ESBC survivors diagnosed 2010-2015 in the South East Health Care region, Sweden and 1768 control women without prior cancer received a postal questionnaire that included the European Organisation for Research and Treatment of Cancer chemotherapy-induced peripheral neuropathy (CIPN20) items. Prevalence, relative risks (RRs) (Poisson regression) and risk factors (binomial regression) were calculated. Adjustments were made for confounding factors (e.g. age, body mass index, comorbidities). Results The response rate was 79% for survivors and 59% for controls. The median time post taxane was 3.6 years (1.5-7.3 years). The adjusted RR was highest (RR 1.8) for "tingling/numbness of toes/feet". Individual sensory symptoms occurred in 8.9-48.4% and motor symptoms in 7.2-61.3% of survivors; the most prevalent symptoms were "difficulty opening jar" and "cramps in feet". Paclitaxel, older age, overweight, diabetes mellitus, vibrating hand tools, autoimmune disease and smoking were independent risk factors. Conclusions PN was more common among ESBC survivors than control women and many symptoms persisted over time. Risk factors should be considered when treatment decisions are made.

Place, publisher, year, edition, pages
Springer Nature, 2021
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-175970 (URN)10.1038/s41416-021-01429-3 (DOI)000652462900002 ()34017086 (PubMedID)
Note

Funding Agencies|Swedish Cancer SocietySwedish Cancer Society [190224]; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [FORSS-932359]; Futurum-The Academy for Health and Care, Jonkoping County Council [575361]; Forsknings-ALF [LIO-901261]

Available from: 2021-06-01 Created: 2021-06-01 Last updated: 2024-03-15
2. Impact of persistent peripheral neuropathy on health-related quality of life among early-stage breast cancer survivors: a population-based cross-sectional study
Open this publication in new window or tab >>Impact of persistent peripheral neuropathy on health-related quality of life among early-stage breast cancer survivors: a population-based cross-sectional study
Show others...
2022 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 195, p. 379-391Article in journal (Refereed) Published
Abstract [en]

Background We explored the impact of persistent sensory and motor taxane-induced peripheral neuropathy (TIPN) symptoms on health-related quality of life (HRQL) among early-stage breast cancer survivors (ESBCS). Methods A population-based cohort of 884 residual-free ESBCS received a postal questionnaire, including the EORTC chemotherapy-induced PN (CIPN20) and the EORTC QLQ-C30 instruments. Mean scores of QLQ-C30 scales among ESBCS with and without TIPN were calculated and adjusted for confounding factors (age, lifestyle factors, co-morbidities; linear regression analyses). Interpretation of QLQ-C30 results were based on guidelines. Results Response rate was 79%, and 646 survivors were included in the analysis. In median, 3.6 (1.5-7.3) years had elapsed post-taxane treatment. All TIPN symptoms had a significant impact on global QoL, which worsened with increased severity of TIPN. Between 29.5% and 93.3% of ESBCS with moderate-severe TIPN reported a clinical important impairment of functioning and personal finances, 64.3-85.7% reporting "difficulty walking because of foot drop," and 53.1-81.3% reporting "problems standing/walking because of difficulty feeling ground under feet" had impaired functioning/finances. The difference in mean scores between affected and non-affected survivors was highest for "numbness in toes/feet" and "difficulty walking because of foot drop." Moderate-severe "difficulty climbing stairs or getting out of chair because of weakness of legs" and "problems standing/walking because of difficulty feeling ground under feet" were associated with the largest clinically important differences on all scales. Conclusion Persistent sensory and motor TIPN is associated with clinically relevant impairment of global QoL, functioning, and personal finances among ESBCS, which increased with level of TIPN severity.

Place, publisher, year, edition, pages
Springer, 2022
Keywords
Adjuvant therapy; Chemotherapy; Taxane; Chemotherapy-Induced Peripheral Neuropathy CIPN; Taxane-induced peripheral neuropathy; Survivorship; Breast cancer survivorship; QLQ-C30; CIPN20; Quality of life; Health-related quality of life; Functional health; Financial toxicity
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:liu:diva-187717 (URN)10.1007/s10549-022-06670-9 (DOI)000837571200001 ()35941422 (PubMedID)
Note

Funding Agencies|Linkoping University; Swedish Cancer Society [190224]; Medical Research Council of Southeast Sweden [FORSS-932359]; FuturumThe Academy for Health and Care, Jonkoping County Council [575361]; Forsknings-ALF [LIO-901261]

Available from: 2022-08-29 Created: 2022-08-29 Last updated: 2024-03-15Bibliographically approved

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