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. 2023 Feb;91(2):157-165.
doi: 10.1007/s00280-022-04499-z. Epub 2023 Jan 4.

The impact of single nucleotide polymorphisms on return-to-work after taxane-based chemotherapy in breast cancer

Cathrine F Hjorth  1 , Per Damkier  2   3   4 , Tore B Stage  5 , Søren Feddersen  3   6 , Stephen Hamilton-Dutoit  7 , Bent Ejlertsen  8   9 , Timothy L Lash  10   11 , Henrik Bøggild  12   13 , Henrik T Sørensen  10 , Deirdre Cronin-Fenton  10
Affiliations

The impact of single nucleotide polymorphisms on return-to-work after taxane-based chemotherapy in breast cancer

Cathrine F Hjorth et al. Cancer Chemother Pharmacol. 2023 Feb.

Abstract

Purpose: Breast cancer treatment is associated with adverse effects, which may delay return-to-work. Single nucleotide polymorphisms (SNPs) may influence the risk and severity of treatment toxicities, which in turn could delay return-to-work. We examined the association of 26 SNPs with return-to-work in premenopausal women with breast cancer.

Methods: Using Danish registries, we identified premenopausal women diagnosed with non-distant metastatic breast cancer during 2007‒2011, assigned adjuvant combination chemotherapy including cyclophosphamide and docetaxel. We genotyped 26 SNPs in 20 genes (ABCB1, ABCC2, ABCG2, CYP1A1, CYP1B1, CYP3A, CYP3A4, CYP3A5, GSTP1, SLCO1B1, SLCO1B3, ARHGEF10, EPHA4, EPHA5, EPHA6, EPHA8, ERCC1, ERCC2, FGD4 and TRPV1) using TaqMan assays. We computed the cumulative incidence of return-to-work (defined as 4 consecutive weeks of work) up to 10 years after surgery, treating death and retirement as competing events and fitted cause-specific Cox regression models to estimate crude hazard ratios (HRs) and 95% confidence intervals (CIs) of return-to-work. We also examined stable labor market attachment (defined as 12 consecutive weeks of work).

Results: We included 1,964 women. No associations were found for 25 SNPs. The cumulative incidence of return-to-work varied by CYP3A5 rs776746 genotype. From 6 months to 10 years after surgery, return-to-work increased from 25 to 94% in wildtypes (n = 1600), from 17 to 94% in heterozygotes (n = 249), and from 7 to 82% in homozygotes (n = 15). The HR showed delayed return-to-work in CYP3A5 rs776746 homozygotes throughout follow-up (0.48, 95% CI 0.26, 0.86), compared with wildtypes. Estimates were similar for stable labor market attachment.

Conclusion: Overall, the SNPs examined in the study did not influence return-to-work or stable labor market attachment after breast cancer in premenopausal women. Our findings did suggest that the outcomes were delayed in homozygote carriers of CYP3A5 rs776746, though the number of homozygotes was low.

Keywords: Breast neoplasms; Cohort study; Docetaxel; Return-to-work; Single nucleotide polymorphisms; Taxane.

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Conflict of interest statement

All authors declare no support in relation to the present study. TBS receives consultancy fees from Pfizer and teaching fees from Orifarm, Eisai, Novartis, and Astellas Pharma. TLL receives consulting fees and travel support for his participation in the Amgen Methods Advisory Council. BE receives institutional grants from AstraZeneca, Eli Lilly, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, and Samsung Bioepis. The Department of Clinical Epidemiology, Aarhus University Hospital, receives funding for other studies from European Medicines Agency and from companies in the form of research grants to (and administered by) Aarhus University.

Figures

Fig. 1
Fig. 1
Cumulative incidence of return-to-work and stable labor market attachment
Fig. 2
Fig. 2
Cumulative incidence of return-to-work (A) and stable labor market attachment (B) by CYP3A5 genotype. Curves were smoothed using loess function. The shaded bands represent associated 95% confidence intervals
Fig. 3
Fig. 3
Hazard ratios with 95% CI of return-to-work (A) and stable labor market attachment (B) in CYP3A5 rs776746 heterozygotes and homozygotes, compared with wildtypes
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