Abstract P5-03-11: The impact of single nucleotide polymorphisms on return-to-work after taxane-based chemotherapy in breast cancer

Abstract

Abstract Background Return-to-work (RTW) after breast cancer may be challenging for breast cancer survivors, especially those who experience adverse effects. Neuropathies are common adverse effect of taxane-based chemotherapy. Single nucleotide polymorphisms (SNPs) in genes related to taxane metabolism and transport, neural function, and neural- or DNA-repair may influence the risk of taxane-induced adverse effects, potentially impacting patient recovery and RTW. We examined the association of such SNPs with RTW in premenopausal breast cancer survivors. Methods We used Denmark’s nationwide population-based health registries to ascertain data on premenopausal women aged 18‒55 years diagnosed with non‒distant metastatic breast cancer during 2007‒2011, who were candidates for adjuvant combination chemotherapy including cyclophosphamide and docetaxel. Only women employed at diagnosis were included. 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. Follow-up continued from the date of primary surgery to the first of RTW (defined as 4 consecutive weeks of work), recurrence, maternity leave/childbirth, other malignancy, retirement, death, emigration or 25th September 2017. We computed the cumulative incidence of RTW and used Cox regression models to calculate unadjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of RTW. Results We included 1,963 women. Women who were homozygotes for the phase 1 metabolizer CYP3A5 rs776746 (n=15) had lower cumulative incidence of RTW than wildtypes (n=1,600) and heterozygotes (n=249), 7%, 25% and 17% at six months, 57%, 87% and 88% at two years, and 82%, 94% and 94% at end of follow-up, respectively. Compared with wildtypes, CYP3A5 rs776746 homozygotes had delayed RTW throughout follow-up (HR 0-10 years: 0.48, 95% CI: 0.26, 0.86). No other SNPs were associated with RTW. Conclusions Among 26 SNPs, CYP3A5 rs776746 was associated with delayed RTW after breast cancer among premenopausal women. 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. Citation Format: Cathrine Hjorth, Per Damkier, Tore B. Stage, Søren Feddersen, Stephen Hamilton-Dutoit, Bent Ejlertsen, Timothy L. Lash, Henrik Bøggild, Henrik Sørensen, Deirdre Cronin-Fenton. The impact of single nucleotide polymorphisms on return-to-work after taxane-based chemotherapy in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-11.