Evidence map›Paper›PMID 25935582›Full record

ArticleBreast cancer research and treatment2015

CYP19A1 polymorphisms and clinical outcomes in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial.

Brian Leyland-Jones, Kathryn P Gray, Mark Abramovitz, Mark Bouzyk, Brandon Young, Bradley Long, Roswitha Kammler, Patrizia Dell'Orto, Maria Olivia Biasi, Beat Thürlimann and 14 more

Open access · greenAbstract read
In one paragraph

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 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 7% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. Pooled it
  2. 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 · 2022
    Trial
  3. Article
  4. Review
  5. Article
  6. 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
  7. Review
  8. Article
  9. Article
  10. Article
  11. Journal of genetics · 2021
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. The Association ofFrontiers in pharmacology · 2017
    Review
  18. Article
  19. Article
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

24 authors at 17 institutions in 9 countries.

Brian Leyland-JonesAvera Cancer Institute, 1000 E 23rd Street, Sioux Falls, SD, 57105, USA, bleylandj@aol.com.
Kathryn P Gray
Mark Abramovitz
Mark Bouzyk
Brandon Young
Bradley Long
Roswitha Kammler
Patrizia Dell'Orto
Maria Olivia Biasi
Beat Thürlimann
Maria B Lyng
Henrik J Ditzel
Vernon J Harvey
Patrick Neven
Isabelle Treilleux
Birgitte Bruun Rasmussen
Rudolf Maibach
Karen N Price
Alan S Coates
Aron Goldhirsch
Olivia Pagani
Giuseppe Viale
James M Rae
Meredith M Regan
European Institute of Oncology · ITAvera Health · USHarvard University · USInternational Breast Cancer Study Group · CHUniversity of Southern Denmark · DKAuckland City Hospital · NZBreast Cancer Trials · AUCentre Léon Bérard · FRFrontier Science & Technology Research Foundation · USHerlev Hospital · DKKantonsspital St. Gallen · CHKU Leuven · BEMichigan Center for Translational Pathology · USMontreal Clinical Research Institute · CASwiss Group For Clinical Cancer Research · CHUniversity of Chicago · USUniversity of Milan · IT

Funding

IBCSG STATISTICAL CENTER--A BREAST CANCER STUDY RESOURCEU24CA075362 · NCI · DANA-FARBER CANCER INSTITUTE · PI REGAN, MEREDITH M · 1997 to 2015
$7.5M
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
NCI NIH HHS CA75362NCI NIH HHS U24 CA075362NIGMS NIH HHS 1R01GM099143NIGMS NIH HHS R01 GM099143
6 · The paper itself

Abstract

To determine whether CYP19A1 polymorphisms are associated with abnormal activity of aromatase and with musculoskeletal and bone side effects of aromatase inhibitors. DNA was isolated from tumor specimens of 4861 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1-98 trial to receive tamoxifen and/or letrozole for 5 years. Tumors were genotyped for six CYP19A1 polymorphisms using PCR-based methods. Associations with breast cancer-free interval (BCFI), distant recurrence-free interval (DRFI), musculoskeletal and bone adverse events (AEs) were assessed using Cox proportional hazards models. All statistical tests were two-sided. No association between the CYP19A1 genotypes and BCFI or DRFI was observed overall. A reduced risk of a breast cancer event for tamoxifen-treated patients with rs700518 variants was observed (BCFI CC/TC vs. TT: HR 0.53, 95 % CI 0.34-0.82, interaction P = 0.08), but not observed for letrozole-treated patients. There was an increased risk of musculoskeletal AEs for patients with rs700518 variants CC/TC versus TT (HR 1.22, 95 % CI 1.03-1.45, P = 0.02), regardless of treatment. Tamoxifen-treated patients with rs4646 variants had a reduced risk of bone AEs (AA/CA vs. CC: HR 0.76, 95 % CI 0.59-0.98), whereas an increase of minor allele (C) of rs10046 was associated with an increased risk of bone AEs (HR 1.28, 95 % CI 1.07-1.52). rs936308 variants were associated with a reduced risk of bone AEs in letrozole-treated patients (GG/GC vs. CC: HR 0.73, 95 % CI 0.54-0.99), different from in tamoxifen-treated patients (GG/GC vs. CC: HR 1.32, 95 % CI 0.92-1.90, interaction P = 0.01). CYP19A1 rs700518 variants showed associations with BCFI, DRFI, in tamoxifen treated patients and musculoskeletal AEs regardless of treatment. SNPs rs4646, rs10046, and rs936308 were associated with bone AEs.

Indexed as

Polymorphism, Single NucleotideAgedAllelesAromataseBiomarkers, TumorBreast NeoplasmsClinical Trials, Phase III as TopicCombined Modality TherapyFemaleGenotypeHumansKaplan-Meier EstimateMiddle AgedNeoplasm GradingNeoplasm MetastasisNeoplasm StagingAromataseBiomarkers, TumorCYP19A1 protein, humanReceptors, EstrogenReceptors, Progesterone

Identifiers

PMID25935582
PMCPMC4763278
OpenAlexW1968846760

What OpenQuestion holds

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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 OpenQuestion graph.