ArticleBreast cancer research and treatment2015
Associations between genetic variants and the effect of letrozole and exemestane on bone mass and bone turnover.
Article in Breast cancer research and treatment, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pharmacogenetics of Toxicities Related to Endocrine Treatment in Breast Cancer: A Systematic Review and Meta-analysis.Cancer genomics & proteomicsPooled it
- No evidence for genotype-treatment interactions with breast cancer endocrine therapy adverse effects in UK Biobank.NPJ breast cancer · 2026Article
- SNP of Aromatase Predict Long-term Survival and Aromatase Inhibitor Toxicity in Patients with Early Breast Cancer: A Biomarker Analysis of the GIM4 and GIM5 Trials.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Article
- Bone Safety Profile of Steroidal Aromatase Inhibitor in Comparison to Nonsteroidal Aromatase Inhibitors in Postmenopausal Women with Breast Cancer: A Network Meta-Analysis.Breast care (Basel, Switzerland) · 2022Article
- Review
- Aromatase Inhibitor-Associated Musculoskeletal Syndrome: Understanding Mechanisms and Management.Frontiers in endocrinology · 2021Review
- Aromatase Inhibitors-Induced Musculoskeletal Disorders: Current Knowledge on Clinical and Molecular Aspects.International journal of molecular sciences · 2020Review
- The Roles of Common Variation and Somatic Mutation in Cancer Pharmacogenomics.Oncology and therapy · 2019Review
- Exemestane may be less detrimental than letrozole to bone health in women homozygous for the UGT2B17*2 gene deletion.Breast cancer research and treatment · 2019Observational
- Osteoporosis and musculoskeletal complications related to therapy of breast cancer.Gland surgery · 2018Review
- Variable aromatase inhibitor plasma concentrations do not correlate with circulating estrogen concentrations in post-menopausal breast cancer patients.Breast cancer research and treatment · 2017Article
- Estrogen receptors in breast and bone: from virtue of remodeling to vileness of metastasis.Oncogene · 2017Review
- Germline genetic predictors of aromatase inhibitor concentrations, estrogen suppression and drug efficacy and toxicity in breast cancer patients.Pharmacogenomics · 2017Review
- ESR1 and PGR polymorphisms are associated with estrogen and progesterone receptor expression in breast tumors.Physiological genomics · 2016Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
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.
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