(32) Return-To-Work in Premenopausal Breast Cancer Patients Prescribed Taxane-Based Chemotherapy. a Population-Based Cohort Study Investigating the Impact of 26 Single Nucleotide Polymorphisms

Sunday, August 28, 2022

8:00 AM – 1:45 PM CEST

Location: Hall C

Publication Number: 1077

Presenting Author(s)

Cathrine F. Hjorth
– MSPH, PhD, Aarhus N, Midtjylland, Denmark

Co-Author(s)

Per Damkier, MD, PhD
– Professor, consultant, Department of Clinical Pharmacology, Odense University Hospital, Denmark and Department of Clinical Research, University of Southern Denmark, Denmark, Denmark
Tore B. Stage
– Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark Odense, Denmark, Denmark
Søren Feddersen
– Biochemist, assistant Professor, MSc, PhD, Department of Clinical Biochemistry, Odense University Hospital, Odense, Denmark, Odense, Syddanmark, Denmark
Stephen Hamilton-Dutoit
– Department of Pathology, Aarhus University Hospital, Aarhus N, Denmark, Denmark
Bent Ejlertsen
– Department of Oncology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark, Denmark
Timothy Lash
– Department of Epidemiology, Emory University, Atlanta, GA, United States
Henrik Bøggild
– Public Health and Epidemiology Group, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark, Denmark
Henrik Toft Sørensen, MD, PhD, DMSc, DSc
– Professor & Chair, Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark, Midtjylland, Denmark
Deirdre Cronin-Fenton
– Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Aarhus, Denmark, Denmark

Background: Taxane-based chemotherapy may induce adverse effects such as neuropathies, which may delay breast cancer survivors’ returning to everyday activities, including work. Return-to-work (RTW) may be a marker of recovery in younger cancer survivors. Genetic polymorphisms in genes encoding for proteins involved in taxane metabolism and transport, neural function, neural- or DNA-repair may influence the risk of taxane-induced adverse effects, impacting patient readiness for RTW.

Objectives: We examined the association of single nucleotide polymorphisms (SNPs) with RTW in premenopausal breast cancer survivors.

Methods: Using Denmark’s nationwide population based health registries, we identified premenopausal women aged 18‒55 years who were employed at diagnosis with non‒distant metastatic breast cancer during 2007‒2011. All women were recommended adjuvant combination chemotherapy including cyclophosphamide and docetaxel. We collected archived tumor tissue from nationwide pathology departments and genotyped 26 SNPs in 20 genes using TaqMan assays. For each SNP, we categorized the women as wildtype, homozygote or heterozygote. We followed all women from primary surgery date to RTW (4 consecutive weeks of work), recurrence, maternity leave/childbirth, other malignancy, retirement, death, emigration or 25th September 2017. We computed cumulative incidence of RTW and fitted Cox regression models to calculate unadjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of RTW. Analyses were repeated for stable labour market attachment (SLMA, 12 consecutive weeks of work).

Results: Among 1,963 women, the cumulative incidence of RTW was 18% at six months, and 53%, 87% and 94% at 1 year, 2 years, and 10 years, respectively. The cumulative incidences varied across CYP3A5 rs776746 wildtypes (n=1,600), heterozygotes (n=249) and homozygotes (n=15) with respectively 25%, 17% and 7% at six months, 53%, 57% and 35% at one year, 87%, 88% and 57% at two years, and 94%,94% and 82% at end of follow-up. Compared with wildtypes, CYP3A5 rs776746 homozygotes had delayed RTW and SLMA throughout follow-up (HRs 0-10 years: 0.48, 95% CI: 0.26, 0.86 and 0.49, 95% CI: 0.27 - 0.88, respectively). No other SNPs were associated with RTW or SLMA.

Conclusions: Among 26 SNPs, the phase 1 metabolizer CYP3A5 rs776746 was associated with delayed RTW and SLMA after premenopausal breast cancer. Our findings may help identify women at risk of a poor clinical course, who may benefit from enhanced supportive care during treatment and follow-up.