ArticleBreast cancer research : BCR2016
Impact of CYP19A1 and ESR1 variants on early-onset side effects during combined endocrine therapy in the TEXT trial.
Article in Breast cancer research : BCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00066703 (A Phase III Trial Evaluating The Role Of Exemestane Plus GnRH Analogue As Adjuvant Therapy For Premenopausal Women With Endocrine Responsive Breast Cancer), which is not on this map. Cited by 16 papers, 4 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.
A Phase III Trial Evaluating The Role Of Exemestane Plus GnRH Analogue As Adjuvant Therapy For Premenopausal Women With Endocrine Responsive Breast Cancer
Who cites it
16 citing papers in PubMed, 4 syntheses or guidelines pooled it, 29 citations in OpenAlex.
- Pooled it
- Genetic Variation and Hot Flashes: A Systematic Review.The Journal of clinical endocrinology and metabolism · 2020Pooled it
- Ovarian suppression for adjuvant treatment of hormone receptor-positive early breast cancer.The Cochrane database of systematic reviews · 2020Pooled it
- Pharmacogenetics of Toxicities Related to Endocrine Treatment in Breast Cancer: A Systematic Review and Meta-analysis.Cancer genomics & proteomicsPooled it
- 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
- ESR1 polymorphisms were associated with aromatase inhibitors induced musculoskeletal symptoms in breast cancer patients.Breast cancer research and treatment · 2026Article
- An Overview of Endometriosis and Potential Pharmacogenetic Targets.Pharmaceutical research · 2026Review
- 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
- 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
- Pharmacogenomics for Prediction of Cardiovascular Toxicity: Landscape of Emerging Data in Breast Cancer Therapies.Cancers · 2022Review
- Managing Common Estrogen Deprivation Side Effects in HR+ Breast Cancer: an Evidence-Based Review.Current oncology reports · 2021Review
- The Roles of Common Variation and Somatic Mutation in Cancer Pharmacogenomics.Oncology and therapy · 2019Review
- Estrogen receptor variant ER-α36 promotes tamoxifen agonist activity in glioblastoma cells.Cancer science · 2019Article
- What's in a name: are menopausal "hot flashes" a symptom of menopause or a manifestation of neurovascular dysregulation?Menopause (New York, N.Y.) · 2018Article
- Germline genetic predictors of aromatase inhibitor concentrations, estrogen suppression and drug efficacy and toxicity in breast cancer patients.Pharmacogenomics · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 9 institutions in 5 countries.
Funding
Abstract
backgroundSingle nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) and cytochrome P450 19A1 (CYP19A1) genes have been associated with breast cancer risk, endocrine therapy response and side effects, mainly in postmenopausal women with early breast cancer. This analysis aimed to assess the association of selected germline CYP19A1 and ESR1 SNPs with early-onset hot flashes, sweating and musculoskeletal symptoms in premenopausal patients enrolled in the Tamoxifen and Exemestane Trial (TEXT).
methodsBlood was collected from consenting premenopausal women with hormone-responsive early breast cancer, randomly assigned to 5-years of tamoxifen plus ovarian suppression (OFS) or exemestane plus OFS. DNA was extracted with QIAamp kits and genotyped for two CYP19A1 (rs4646 and rs10046) and three ESR1 (rs2077647, rs2234693 and rs9340799) SNPs by a real-time pyrosequencing technique. Adverse events (AEs) were recorded at baseline and 3-monthly during the first year. Associations of the genotype variants with grade ≥2 early-onset targeted AEs of hot flashes/sweating or musculoskeletal events were assessed using logistic regression models.
resultsThere were 2660 premenopausal patients with breast cancer in the intention-to-treat population of TEXT, and 1967 (74 %) are included in this translational study. The CYP19A1 rs10046 variant T/T, represented in 23 % of women, was associated with a reduced incidence of grade ≥2 hot flashes/sweating (univariate odds ratio (OR) = 0.78; 95 % CI 0.63-0.97; P = 0.03), more strongly in patients assigned exemestane + OFS (TT vs CT/CC: OR = 0.65, 95 % CI = 0.48-0.89) than assigned tamoxifen + OFS (OR = 0.94, 95 % CI = 0.69-1.27, interaction P = 0.03). No association with any of the CYP19A1/ESR1 genotypes and musculoskeletal AEs was found.
conclusionThe CYP19A1 rs10046 variant T/T favors lower incidence of hot flashes/sweating under exemestane + OFS treatment, suggesting endocrine-mediated effects. Based on findings from others, this SNP may potentially enhance treatment adherence and treatment efficacy. We plan to evaluate the clinical impact of this polymorphism during time, pending sufficient median follow up.
trial registrationClinicalTrials.gov NCT00066703, registered August 6, 2003.
Indexed as
Identifiers
What OpenQuestion holds
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.