Trial reportBreast cancer research and treatment2013
Genetic associations with toxicity-related discontinuation of aromatase inhibitor therapy for breast cancer.
Trial report in Breast cancer research and treatment, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 3 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- The impact of medication side effects on adherence and persistence to hormone therapy in breast cancer survivors: A quantitative systematic review.Breast (Edinburgh, Scotland) · 2022Pooled it
- Influence of CYP19A1 polymorphisms on the treatment of breast cancer with aromatase inhibitors: a systematic review and meta-analysis.BMC medicine · 2015Pooled it
- Pharmacogenetics of Toxicities Related to Endocrine Treatment in Breast Cancer: A Systematic Review and Meta-analysis.Cancer genomics & proteomicsPooled it
- Genome-wide association study of aromatase inhibitor discontinuation due to musculoskeletal symptoms.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022Trial
- A randomized, double-blind, placebo-controlled trial of testosterone for treatment of postmenopausal women with aromatase inhibitor-induced arthralgias: Alliance study A221102.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2021Trial
- Influence of body weight and UGT2B7 polymorphism on varenicline exposure in a cohort of smokers from the general population.European journal of clinical pharmacology · 2019Trial
- Prospective assessment of patient-reported outcomes and estradiol and drug concentrations in patients experiencing toxicity from adjuvant aromatase inhibitors.Breast cancer research and treatment · 2017Trial
- Association of Variants in Candidate Genes with Lipid Profiles in Women with Early Breast Cancer on Adjuvant Aromatase Inhibitor Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- Treatment-associated musculoskeletal and vasomotor symptoms and relapse-free survival in the NCIC CTG MA.27 adjuvant breast cancer aromatase inhibitor trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Trial
- Baseline gene expression and dynamic endocrine therapy use in ER+ breast cancer: associations with recurrence in a real-world cohort.Research square · 2026Article
- ESR1 polymorphisms were associated with aromatase inhibitors induced musculoskeletal symptoms in breast cancer patients.Breast cancer research and treatment · 2026Article
- ESR1 Variants and Subcontinental Genomic Ancestry: Insights from the 1000 Genomes Project and Native American Populations.Clinical pharmacology and therapeutics · 2025Article
- Musculoskeletal symptoms associated with aromatase inhibitors in the treatment of early breast cancer: A scoping review of risk factors and outcomes.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Article
- Article
- Adverse Event Profiles of the Third-Generation Aromatase Inhibitors: Analysis of Spontaneous Reports Submitted to FAERS.Biomedicines · 2024Article
- A Cohort Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms: Results from ECOG-ACRIN E1Z11.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Incorporation of emergent symptoms and genetic covariates improves prediction of aromatase inhibitor therapy discontinuation.JAMIA open · 2024Article
- 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
- Aromatase inhibitor-associated musculoskeletal pain: An overview of pathophysiology and treatment modalities.SAGE open medicine · 2022Review
- Pharmacogenetics of Breast Cancer Treatments: A Sub-Saharan Africa Perspective.Pharmacogenomics and personalized medicine · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 7 institutions in 1 country.
Funding
Abstract
Up to 25 % of patients discontinue adjuvant aromatase inhibitor (AI) therapy due to intolerable symptoms. Predictors of which patients will be unable to tolerate these medications have not been defined. We hypothesized that inherited variants in candidate genes are associated with treatment discontinuation because of AI-associated toxicity. We prospectively evaluated reasons for treatment discontinuation in women with hormone receptor-positive breast cancer initiating adjuvant AI through a multicenter, prospective, randomized clinical trial of exemestane versus letrozole. Using multiple genetic models, we evaluated potential associations between discontinuation of AI therapy because of toxicity and 138 variants in 24 candidate genes, selected a priori, primarily with roles in estrogen metabolism and signaling. To account for multiple comparisons, statistical significance was defined as p < 0.00036. Of the 467 enrolled patients with available germline DNA, 152 (33 %) discontinued AI therapy because of toxicity. Using a recessive statistical model, an intronic variant in ESR1 (rs9322336) was associated with increased risk of musculoskeletal toxicity-related exemestane discontinuation [HR 5.0 (95 % CI 2.1-11.8), p < 0.0002]. An inherited variant potentially affecting estrogen signaling may be associated with exemestane-associated toxicity, which could partially account for intra-patient differences in AI tolerability. Validation of this finding is required.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.