Evidence map›Paper›PMID 40399999›Full record

ArticleBreast cancer research : BCR2025

Distribution of age at natural menopause, age at menarche, menstrual cycle length, height and BMI in BRCA1 and BRCA2 pathogenic variant carriers and non-carriers: results from EMBRACE.

Nasim Mavaddat, Debra Frost, Emily Zhao, Daniel R Barnes, Munaza Ahmed, Julian Barwell, Angela F Brady, Paul Brennan, Hector Conti, Jackie Cook and 24 more

Abstract read
In one paragraph

Article in Breast cancer research : BCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

34 authors.

Nasim MavaddatDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK. nm274@medschl.cam.ac.uk.
Debra FrostDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
Emily ZhaoDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
Daniel R BarnesDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
Munaza AhmedNorth East Thames Regional Clinical Genetics Service, Great Ormond Street Hospital, London, UK.
Julian BarwellLeicestershire, Northamptonshire and Rutland Clinical Genetics Service, University Hospitals of Leicester NHS Trust, Leicester, UK.
Angela F BradyNorth West Thames Regional Genetics Service, London North West University Healthcare NHS Trust, London, UK.
Paul BrennanNorthern Genetics Service, Newcastle Upon Tyne NHS Foundation Trust, Newcastle Upon Tyne, UK.
Hector ContiAll Wales Medical Genomics Services, Wrexham Maelor Hospital, Wrexham, UK.
Jackie CookSheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, UK.
Harriet CopelandDepartment Clinical Genetics, Royal Devon University Healthcare NHS Foundation Trust, Exeter, Devon, UK.
Rosemarie DavidsonDepartment of Clinical Genetics, South Glasgow University Hospitals, Glasgow, UK.
Alan DonaldsonClinical Genetics Department, St Michael's Hospital, Bristol, UK.
Emma DouglasWest Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, Birmingham, UK.
David GallagherTrinity St Jame's Cancer Institute, Cancer Genetics Service, Dublin, Ireland.
Rachel HartLiverpool Women's Hospital Cheshire and Merseyside Genetics, Liverpool Women's NHS Foundation Trust, Liverpool, UK.
Louise IzattClinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
Zoe KempRoyal Marsden Hospital, NHS Trust, London, England, UK.
Fiona LallooClinical Genetics Service, Manchester Centre for Genomic Medicine, Manchester University Hospitals Foundation Trust, Manchester, UK.
Zosia MiedzybrodzkaNHS Grampian, North of Scotland Regional Genetics Service, Aberdeen, Scotland, UK.
Patrick J MorrisonBelfast Health and Social Care Trust, Clinical Genetics Service, Belfast, Northern Ireland, UK.
Jennie E MurraySouth East Scotland Clinical Genetics Service, Western General Hospital, Edinburgh, UK.
Alex MurrayAll Wales Medical Genomics Service, Wales Genomic Health Centre, Cardiff, UK.
Hannah MusgraveLeeds Genomic Medicine Service, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Claire SearleDepartment of Clinical Genetics, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Lucy SideUniversity Hospital Southampton NHS Trust and Princess Anne Hospital, Southampton, UK.
Katie SnapeMedical Genetics Unit, St George's, University of London, London, UK.
Vishakha TripathiClinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
Lisa WalkerOxford Centre for Genomic Medicine, Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Stephanie ArcherDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
D Gareth EvansGenomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution, Infection and Genomic Science, University of Manchester, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
Marc TischkowitzDepartment of Genomic Medicine, Cambridge Biomedical Research Centre, National Institute for Health Research, University of Cambridge, Cambridge, UK.
Antonis C AntoniouDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
Douglas F EastonDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.

Funding

Cancer Research UK A26886Cancer Research UK PPRPGM-Nov20\100002Cancer Research UK PRCPJT-Nov21\100004Manchester National Institute for Health Research Manchester Biomedical Research Centre NIHR203308NIHR Cambridge Biomedical Research Centre NIHR203312
6 · The paper itself

Abstract

backgroundCarriers of germline pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are at higher risk of developing breast and ovarian cancer than the general population. It is unclear if these PVs influence other breast or ovarian cancer risk factors, including age at menopause (ANM), age at menarche (AAM), menstrual cycle length, BMI or height. There is a biological rationale for associations between BRCA1 and BRCA2 PVs and reproductive traits, for example involving DNA damage and repair mechanisms. The evidence for or against such associations is limited.

methodsWe used data on 3,046 BRCA1 and 3,264 BRCA2 PV carriers, and 2,857 non-carrier female relatives of PV carriers from the Epidemiological Study of Familial Breast Cancer (EMBRACE). Associations between ANM and PV carrier status was evaluated using linear regression models allowing for censoring. AAM, menstrual cycle length, BMI, and height in carriers and non-carriers were compared using linear and multinomial logistic regression. Analyses were adjusted for potential confounders, and weighted analyses carried out to account for non-random sampling with respect to cancer status.

resultsNo statistically significant difference in ANM between carriers and non-carriers was observed in analyses accounting for censoring. Linear regression effect sizes for ANM were -0.002 (95%CI: -0.401, 0.397) and -0.172 (95%CI: -0.531, 0.188), for BRCA1 and BRCA2 PV carriers respectively, compared with non-carrier women. The distributions of AAM, menstrual cycle length and BMI were similar between PV carriers and non-carriers, but BRCA1 PV carriers were slightly taller on average than non-carriers (0.5 cm difference, p = 0.003).

conclusionInformation on the distribution of cancer risk factors in PV carriers is needed for incorporating these factors into multifactorial cancer risk prediction algorithms. Contrary to previous reports, we found no evidence that BRCA1 or BRCA2 PV are associated with hormonal or anthropometric factors, except for a weak association with height. We highlight methodological considerations and data limitations inherent in studies aiming to address this question.

Indexed as

BRCA1 ProteinBRCA2 ProteinBreast NeoplasmsMenarcheMenopauseMenstrual CycleAdultAgedAge FactorsBody HeightBody Mass IndexFemaleGenetic Predisposition to DiseaseGerm-Line MutationHeterozygoteHumansBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanBody mass indexBRCA1BRCA2CancerHeightMenarcheMenopause

Identifiers

PMID40399999
PMCPMC12093752

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.