Single-nucleotide polymorphisms and the effectiveness of taxane-based chemotherapy in premenopausal breast cancer: a population-based cohort study in Denmark.
Female
Humans
Breast Neoplasms
/ drug therapy
Bridged-Ring Compounds
Chemotherapy, Adjuvant
Cohort Studies
Cytochrome P-450 CYP3A
/ therapeutic use
Denmark
/ epidemiology
Docetaxel
/ therapeutic use
Liver-Specific Organic Anion Transporter 1
Neoplasm Recurrence, Local
/ drug therapy
Polymorphism, Single Nucleotide
Taxoids
/ therapeutic use
Breast neoplasm
Mortality
Neoplasm recurrence
Single-nucleotide polymorphisms
Taxanes
Journal
Breast cancer research and treatment
ISSN: 1573-7217
Titre abrégé: Breast Cancer Res Treat
Pays: Netherlands
ID NLM: 8111104
Informations de publication
Date de publication:
Jul 2022
Jul 2022
Historique:
received:
03
02
2022
accepted:
04
04
2022
pubmed:
3
5
2022
medline:
1
7
2022
entrez:
2
5
2022
Statut:
ppublish
Résumé
Taxane-based chemotherapy is the primary treatment for premenopausal breast cancer. Although being inconsistent, research suggests that variant alleles alter pharmacokinetics through reduced function of OATP transporters (limiting hepatic uptake), CYP-450 enzymes (hampering drug metabolism), and ABC transporters (decreasing clearance). Reduced function of DNA repair enzymes may hamper effectiveness through dose-limiting toxicities. We investigated whether single-nucleotide polymorphisms (SNPs) were associated with breast cancer recurrence or mortality in premenopausal women diagnosed with breast cancer. We conducted a population-based cohort study of premenopausal women diagnosed with non-distant metastatic breast cancer in Denmark during 2007‒2011, when guidelines recommended adjuvant combination chemotherapy (taxanes, anthracyclines, and cyclophosphamide). Using archived formalin-fixed paraffin-embedded primary tumor tissue, we genotyped 26 SNPs using TaqMan assays. Danish health registries provided data on breast cancer recurrence (through September 25, 2017) and death (through December 31, 2019). We fit Cox regression models to calculate crude hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and mortality across genotypes. Among 2,262 women, 249 experienced recurrence (cumulative incidence: 13%) and 259 died (cumulative incidence: 16%) during follow-up (median 7.0 and 10.1 years, respectively). Mortality was increased in variant carriers of GSTP1 rs1138272 (HR: 1.30, 95% CI 0.95-1.78) and CYP3A rs10273424 (HR: 1.33, 95% CI 0.98-1.81). SLCO1B1 rs2306283 (encoding OATP1B1) variant carriers had decreased recurrence (HR: 0.82, 95% CI 0.64-1.07) and mortality (HR: 0.77, 95% CI 0.60-0.98). Docetaxel effectiveness was influenced by SNPs in GSTP1, CYP3A, and SLCO1B1 in premenopausal women with non-distant metastatic breast cancer, likely related to altered docetaxel pharmacokinetics. These SNPs may help determine individual benefit from taxane-based chemotherapy.
Identifiants
pubmed: 35501422
doi: 10.1007/s10549-022-06596-2
pii: 10.1007/s10549-022-06596-2
pmc: PMC9239972
doi:
Substances chimiques
Bridged-Ring Compounds
0
Cytochrome P-450 CYP3A
EC 1.14.14.1
Docetaxel
15H5577CQD
Liver-Specific Organic Anion Transporter 1
0
SLCO1B1 protein, human
0
taxane
1605-68-1
Taxoids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
353-363Subventions
Organisme : Kræftens Bekæmpelse
ID : R167-A11045-17-S2
Organisme : Dansk Kræftforsknings Fond
ID : PLESNER-FAST-Active.FID1839672
Organisme : Lundbeckfonden
ID : R167-2013-15861
Organisme : US National Cancer Institute
ID : R01CA16682
Informations de copyright
© 2022. The Author(s).
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