Associations between genetic variants and the effect of letrozole and exemestane on bone mass and bone turnover
| Autor: | Jessica Dantzer, Daniel F. Hayes, Santosh Philips, Thomas N. Hangartner, Vered Stearns, N. Lynn Henry, Kelley M. Kidwell, David A. Flockhart, Munro Peacock, Catherine Van Poznak, Zeruesenay Desta, Todd C. Skaar, Anne T. Nguyen, Steffi Oesterreich, Lang Li, Anna Maria Storniolo, James M. Rae |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Adult
Cancer Research medicine.medical_specialty Bone density Antineoplastic Agents Hormonal Genotype Breast Neoplasms Polymorphism Single Nucleotide Bone and Bones Article Bone remodeling chemistry.chemical_compound Breast cancer Exemestane Bone Density Internal medicine Nitriles medicine Adjuvant therapy Humans Aromatase Alleles Genetic Association Studies Aged Bone mineral Aged 80 and over biology business.industry Aromatase Inhibitors Letrozole Genetic Variation Middle Aged Triazoles medicine.disease Androstadienes Postmenopause Endocrinology Oncology chemistry biology.protein Female Bone Remodeling business Biomarkers medicine.drug |
| Zdroj: | Breast cancer research and treatment. 154(2) |
| ISSN: | 1573-7217 |
| Popis: | Adjuvant therapy for hormone receptor (HR) positive postmenopausal breast cancer patients includes aromatase inhibitors (AI). While both the non-steroidal AI letrozole and the steroidal AI exemestane decrease serum estrogen concentrations, there is evidence that exemestane may be less detrimental to bone. We hypothesized that single nucleotide polymorphisms (SNP) predict effects of AIs on bone turnover. Early stage HR-positive breast cancer patients were enrolled in a randomized trial of exemestane versus letrozole. Effects of AI on bone mineral density (BMD) and bone turnover markers (BTM), and associations between SNPs in 24 candidate genes and changes in BMD or BTM were determined. Of the 503 enrolled patients, paired BMD data were available for 123 and 101 patients treated with letrozole and exemestane, respectively, and paired BTM data were available for 175 and 173 patients, respectively. The mean change in lumbar spine BMD was significantly greater for letrozole-treated (-3.2 %) compared to exemestane-treated patients (-1.0 %) (p = 0.0016). Urine N-telopeptide was significantly increased in patients treated with exemestane (p = 0.001) but not letrozole. Two SNPs (rs4870061 and rs9322335) in ESR1 and one SNP (rs10140457) in ESR2 were associated with decreased BMD in letrozole-treated patients. In the exemestane-treated patients, SNPs in ESR1 (Rs2813543) and CYP19A1 (Rs6493497) were associated with decreased bone density. Exemestane had a less negative impact on bone density compared to letrozole, and the effects of AI therapy on bone may be impacted by genetic variants in the ER pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink