ArticlePloS one2017
Polymorphisms associated with everolimus pharmacokinetics, toxicity and survival in metastatic breast cancer.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses 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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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.
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- A systematic review and meta-analysis of the impacts of germline pharmacogenomics on severe toxicity and symptom burden in adult patients with cancer.Clinical and translational science · 2024Pooled it
- Identification of key genes in osteosarcoma by meta‑analysis of gene expression microarray.Molecular medicine reports · 2019Pooled it
- Interaction between CYP3A4 gene polymorphism and obesity on breast cancer susceptibility in Chinese women.Environmental health and preventive medicine · 2025Article
- Everolimus Through Plasmatic Concentrations in Cancer Patients: Prospective Longitudinal Observational Multicentric Study (DIANA-1 Project).Journal of clinical medicine · 2024Article
- CYP3A4*1B but Not CYP3A5*3 as Determinant of Long-Term Tacrolimus Dose Requirements in Spanish Solid Organ Transplant Patients.International journal of molecular sciences · 2024Article
- Recent Advances with Precision Medicine Treatment for Breast Cancer including Triple-Negative Sub-Type.Cancers · 2023Review
- Pharmacogenomics for Prediction of Cardiovascular Toxicity: Landscape of Emerging Data in Breast Cancer Therapies.Cancers · 2022Review
- Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Drug Repurposing in Cancer Therapy: Influence of Patient's Genetic Background in Breast Cancer Treatment.International journal of molecular sciences · 2022Review
- Everolimus pharmacokinetics and exposure-response relationship in Japanese patients with advanced breast cancer.Frontiers in pharmacology · 2022Article
- Metformin Potentiates the Anticancer Effect of Everolimus on Cervical Cancer In Vitro and In Vivo.Cancers · 2021Article
- An Example of Personalized Treatment in HR+ HER2+ Long Survivor Breast Cancer Patient (Case Report).Current oncology (Toronto, Ont.) · 2021Article
- Review
- Prognostic Factors in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative (HR+/HER2-) Advanced Breast Cancer: A Systematic Literature Review.Cancer management and research · 2021Review
- Effect of genetic polymorphisms in CYP3A4, CYP3A5, and m-TOR on everolimus blood exposure and clinical outcomes in cancer patients.The pharmacogenomics journal · 2020Observational
- Association of CYP gene polymorphisms with breast cancer risk and prognostic factors in the Jordanian population.BMC medical genetics · 2019Article
- Correlations between CYP3A4 polymorphism and susceptibility to breast cancer in Chinese Han population.International journal of clinical oncology · 2019Article
- Precision medicine based on tumorigenic signaling pathways for triple-negative breast cancer.Oncology letters · 2018Review
- Genetic polymorphisms associated with adverse reactions of molecular-targeted therapies in renal cell carcinoma.Medical oncology (Northwood, London, England) · 2018Review
- Katanin P80 expression correlates with lymph node metastasis and worse overall survival in patients with breast cancer.Cancer biomarkers : section A of Disease markers · 2018Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMetastatic breast cancer (MBC) progressing after endocrine therapy frequently activates PI3K/AKT/mTOR pathway. The BOLERO-2 trial showed that everolimus-exemestane achieves increased progression free survival (PFS) compared with exemestane. However, there is great inter-patient variability in toxicity and response to exemestane-everolimus treatment. The objective of this study was to perform an exploratory study analyzing the implication of single nucleotide polymorphisms (SNPs) on outcomes from this treatment through a pharmacogenetic analysis. PATIENTS AND
methodsBlood was collected from 90 postmenopausal women with hormone receptor-positive, HER2-negative MBC treated with exemestane-everolimus following progression after prior treatment with a non-steroidal aromatase inhibitor. Everolimus pharmacokinetics was measured in 37 patients. Twelve SNPs in genes involved in everolimus pharmacokinetics and pharmacodynamics were genotyped and associations assessed with drug plasma levels, clinically relevant toxicities (non-infectious pneumonitis, mucositis, hyperglycemia and hematological toxicities), dose reductions or treatment suspensions due to toxicity, progression free survival (PFS) and overall survival.
resultsWe found that CYP3A4 rs35599367 variant (CYP3A4*22 allele) carriers had higher everolimus blood concentration compared to wild type patients (P = 0.019). ABCB1 rs1045642 was associated with risk of mucositis (P = 0.031), while PIK3R1 rs10515074 and RAPTOR rs9906827 were associated with hyperglycemia and non-infectious pneumonitis (P = 0.016 and 0.024, respectively). Furthermore, RAPTOR rs9906827 was associated with PFS (P = 0.006).
conclusionsCYP3A4*22 allele influenced plasma concentration of everolimus and several SNPs in PI3K/AKT/mTOR pathway genes were associated with treatment toxicities and prognosis. These results require replication, but suggest that germline variation could influence everolimus outcomes in MBC.
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