Evidence map›Paper›PMID 35776183›Full record

Trial reportSupportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer2022

Genome-wide association study of aromatase inhibitor discontinuation due to musculoskeletal symptoms.

Daniel L Hertz, Julie A Douglas, Robert M Miller, Kelley M Kidwell, Christina L Gersch, Zeruesenay Desta, Anna Maria Storniolo, Vered Stearns, Todd C Skaar, Daniel F Hayes and 2 more

Open access · greenAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 20% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. 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 · 2025
    Article
  8. Article
  9. Advances of autoimmune rheumatic diseases related to malignant tumors.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 1 country.

Daniel L HertzDepartment of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church St., Room 3054, Ann Arbor, MI, 48109-1065, USA. DLHertz@med.umich.edu.
Julie A DouglasDepartment of Mathematics and Statistics, Skidmore College, Saratoga Springs, NY, 12866, USA.
Robert M MillerDepartment of Mathematics and Statistics, Skidmore College, Saratoga Springs, NY, 12866, USA.
Kelley M KidwellDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Christina L GerschDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
Zeruesenay DestaIndiana University School of Medicine, Indianapolis, IN, USA.
Anna Maria StornioloIndiana University School of Medicine, Indianapolis, IN, USA.
Vered StearnsJohns Hopkins School of Medicine, Baltimore, MD, USA.
Todd C SkaarIndiana University School of Medicine, Indianapolis, IN, USA.
Daniel F HayesDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
N Lynn HenryDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
James M RaeDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
University of Michigan–Ann Arbor · USIndiana University School of MedicineSkidmore College · USIndiana University – Purdue University Indianapolis · USJohns Hopkins University · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Eric R. Fearon · 1988 to 2026
$178.2M
QAQC Johns Hopkins Institute for Clinical and Translational ResearchUL1TR003098 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2019 to 2023
$57.7M
ZINC GLUCONATE GLYCINE LOZENGES &VITAMIN C EFFECTS ON COMMON COLDM01RR000042 · NCRR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI YANIK, GREGORY A · 1985 to 2007
$40.8M
ZINC AND CA EDTA THERAPY OF PLUMBISMM01RR000052 · NCRR · JOHNS HOPKINS UNIVERSITY · PI VINING, EILEEN PATRICE · 1985 to 2007
$37.3M
ZOSUQUIDAR TRIHYDROCHLORIDE DURING CONVENTIONAL INDUCTION AND POST-REMISSIONM01RR000750 · NCRR · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TISDALE, JAMES E. · 1985 to 2008
$25.5M
TAMAXIFEN PHARMACOGENETICSU01GM061373 · NIGMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI FLOCKHART, DAVID ALASTAIR · 2000 to 2009
$17.0M
Indiana University Comprehensive Training in Clinical PharmacologyT32GM008425 · NIGMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI Zeruesenay Desta, Michael Thomas Eadon · 1992 to 2026
$7.7M
Biostatistics Training Program in Cancer ResearchT32CA083654 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Veerabhadran Baladandayuthapani, Kelley McLain Kidwell · 2002 to 2026
$4.3M
Genetic Predictors of Anti-Estrogen Clinical Activity in Breast Cancer PatientsR01GM099143 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RAE, JAMES MICHAEL · 2011 to 2015
$1.6M
Inflammatory oxylipins and aromatase inhibitor toxicity in breast cancerR21CA251343 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HENRY, NORAH LYNN · 2021 to 2021
$428k
NCATS NIH HHS UL1 TR003098NCI NIH HHS 5T32CA083654NCI NIH HHS P30 CA046592NCI NIH HHS R21 CA251343NCI NIH HHS T32 CA083654NCRR NIH HHS M01 RR000042NCRR NIH HHS M01-RR000042NCRR NIH HHS M01 RR000052NCRR NIH HHS M01-RR00052NCRR NIH HHS M01 RR000750NCRR NIH HHS M01-RR00750NIGMS NIH HHS 5T32-GM08425NIGMS NIH HHS GM099143NIGMS NIH HHS R01 GM099143NIGMS NIH HHS T32 GM008425NIGMS NIH HHS U01 GM061373NIGMS NIH HHS U-01 GM61373
6 · The paper itself

Abstract

objectiveAromatase inhibitors (AIs) are commonly used to treat hormone receptor positive (HR +) breast cancer. AI-induced musculoskeletal syndrome (AIMSS) is a common toxicity that causes AI treatment discontinuation. The objective of this genome-wide association study (GWAS) was to identify genetic variants associated with discontinuation of AI therapy due to AIMSS and attempt to replicate previously reported associations.

methodsIn the Exemestane and Letrozole Pharmacogenetics (ELPh) study, postmenopausal patients with HR + non-metastatic breast cancer were randomized to letrozole or exemestane. Genome-wide genotyping of germline DNA was conducted followed by imputation. Each imputed variant was tested for association with time-to-treatment discontinuation due to AIMSS using a Cox proportional hazards model assuming additive genetic effects and adjusting for age, baseline pain score, prior taxane treatment, and AI arm. Secondary analyses were conducted within each AI arm and analyses of candidate variants previously reported to be associated with AIMSS risk.

resultsFour hundred ELPh participants were included in the combined analysis. Two variants surpassed the genome-wide significance level in the primary analysis (p value < 5 × 10

conclusionsOur GWAS findings identify several candidate variants that may be associated with AIMSS risk from AI generally or letrozole specifically. Validation of these associations in independent cohorts is needed before translating these findings into clinical practice to improve treatment outcomes in patients with HR + breast cancer.

Indexed as

Aromatase InhibitorsBreast NeoplasmsFemaleGenome-Wide Association StudyHumansLetrozoleTaxoidsAromatase InhibitorsLetrozoleTaxoidsAdherenceAromatase inhibitorBreast cancerGenome-wide association study (GWAS)Musculoskeletal adverse effectsPharmacogeneticTreatment discontinuation

Identifiers

PMID35776183
PMCPMC9529953
OpenAlexW4283742262

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.