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Results from London Regional Clinical Genetics services over a 5-year period on germline TP53 testing in women diagnosed with breast cancer at <30 years
  1. Alice Garrett1,
  2. Sabrina Talukdar2,
  3. Louise Izatt3,
  4. Angela F Brady4,
  5. Sinead Whyte4,
  6. Katherine S Josephs2,
  7. Monisha Shanmugasundaram5,
  8. Li Shan Guillemot6,
  9. Dara Vakili7,
  10. Shevaun Ey8,
  11. Munaza Ahmed1
  1. 1North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
  2. 2South West Thames Regional Genetics Service, St George's University Hospitals NHS Foundation Trust, London, UK
  3. 3South East Thames Regional Genetics Service, Guy's and St Thomas' NHS Foundation Trust, London, UK
  4. 4North West Thames Regional Genetics Service, London North West University Healthcare NHS Trust, Harrow, UK
  5. 5West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
  6. 6Faculty of Biology Medicine and Health, The University of Manchester, Manchester, UK
  7. 7Institute of Child Health, University College London, London, UK
  8. 8Australian National University Medical School, Australian National University, Canberra, Australian Capital Territory, Australia
  1. Correspondence to Dr Munaza Ahmed, North East Thames Regional Genetics Service, Great Ormond Street Hospital For Children NHS Foundation Trust, London, UK; Munaza.Ahmed{at}gosh.nhs.uk
  • Present affiliation The present affiliation of Alice Garrett is: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK

  • Present affiliation The present affiliation of Sinead Whyte is: North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

Abstract

Background The most common cancer diagnosed in germline TP53 pathogenic variant (PV) carriers is premenopausal breast cancer. An increased rate of breast tumour HER2 positivity has been reported in this group. Screening for breast/other cancers is recommended in PV carriers.

Objectives 1. To assess the frequency of germline TP53 PVs reported diagnostically in women with breast cancer at <30 years of age.

2. To evaluate the impact of personal/family history and HER2 status on the likelihood of germline TP53 pathogenic/likely pathogenic variant (PV/LPV) identification.

Methods Genetic test results from patients undergoing diagnostic germline TP53 tests between 2012 and 2017 in the four London Regional Clinical Genetics Services were reviewed. Clinical/pathology data and family history were extracted from genetics files for women diagnosed with breast cancer at <30 years.

Results The overall germline TP53 PV/LPV variant detection rate was 9/270=3.3% in all women diagnosed with breast cancer at <30 years and 2/171=1.2% in those with no second/subsequent cancer diagnosis or family history of TP53-spectrum cancers. Breast cancers were significantly more likely to be HER2-positive in TP53 PV/LPV carriers than in non-carriers (p=0.00006).

Conclusions Germline TP53 PVs/LPVs are uncommon among women diagnosed with breast cancer aged <30 years without other relevant personal or family cancer history but have an important clinical impact when identified.

  • genetic testing
  • genetics
  • medical
  • germ-line mutation
  • sequence analysis

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Footnotes

  • Contributors The project was conceived and planned by MA. Data were collected by ST, LI, AFB, SW, KSJ, MS, LSG, DV, SE and MA. Data analysis was conducted by AG. The manuscript was drafted by AG and MA. All authors contributed to the final manuscript.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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