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  • Germline testing for breast cancer patients in England: illogical to prioritise grade 1 breast cancer aged 30–39 over grade 3 aged 40–49 years?

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Cancer genetics
Brief communication
Germline testing for breast cancer patients in England: illogical to prioritise grade 1 breast cancer aged 30–39 over grade 3 aged 40–49 years?
  1. D Gareth Evans1,2,
  2. Sacha J Howell2,3,
  3. George J Burghel4,
  4. Claire Forde5,
  5. Fiona Lalloo6,
  6. Miriam J Smith7,
  7. Anthony Howell8,
  8. Ashu Gandhi9,
  9. Emma Roisin Woodward10
  1. 1 Genomic Medicine, University of Manchester - The Victoria University of Manchester Campus, Manchester, UK
  2. 2 Manchester Academic Health Science Centre, Manchester, UK
  3. 3 The Christie NHS Foundation Trust, Manchester, UK
  4. 4 Genomic Diagnostic Laboratory, Manchester University NHS Foundation Trust, Manchester, UK
  5. 5 Clinical Genetics Service, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  6. 6 Clinical Genetics Service, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  7. 7 Genetic Medicine, University of Manchester, Manchester, UK
  8. 8 Prevent Breast Cancer Centre, Manchester, UK
  9. 9 Prevent Breast Cancer Centre, Prevent Breast Cancer Centre, Wythenshawe Hospital Manchester Universities Foundation Trust, Wythenshawe, Manchester, UK
  10. 10 Manchester Centre for Genomic Medicine, Central Manchester NHS Foundation Trust, Manchester, UK
  1. Correspondence to Professor D Gareth Evans; gareth.d.evans{at}manchester.ac.uk

https://doi.org/10.1136/jmg-2024-110183

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    Germline genetic testing for pathogenic variants (PVs) in breast cancer (BC) genes is currently triggered by algorithms that assess the likelihood of PVs in specific patient populations.1 Testing in patients with BC in England was updated in April 2022, making it more widely available, including all women diagnosed <40 years, except those with grade 1 disease.2 However, this exception was recently dropped, apparently to simplify the testing algorithm. We have assessed the likelihood of a PV in BRCA1/2 in grade 1 versus grade 3 ER+HER2- breast cancer showing much higher rates in older women (40–49 years) with grade 3 disease than those <40 with grade 1.

    Genetic testing strategies for BC in Europe are primarily targeted at individuals affected with cancer based on PV likelihood with testing of relatives usually only offered if a PV is identified in an index relative.1 More recently, European guidelines are now driven by the potential for gene-level directed management strategies such as poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) in persons with BC.3 In view of the evidence of efficacy for PARPi in earlier stage BC,4 further expansion of the testing criteria is likely to be implemented. A key question is whether this should be offered to all people with BC or whether a threshold should still be used, based on overall likelihood of PV detection, potentially incorporating likely future benefit from PARPi.

    We have shown very low rates of PVs in patients with grade 1 breast cancer (G1BC) (0/156) in a population-based study of 1061 women with BCs5 compared with 11 out of 152 (7.2%) for patients with ER+HER2- G3BC (p=0.0003). We have also demonstrated …

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    Footnotes

    • X @BurghelG, @ER_Woodward

    • Contributors Conception and design: DGE. Acquisition of data: DGE. Analysis and interpretation of data: DGE. Drafting: DGE. Manuscript review: All. Approval of final submission: All. Guarantor: DGE.

    • Funding MFT research was funded by the Manchester National Institute for Health Research (NIHR) Biomedical Research Centre (IS-BRC-1215-20007). BRCA-DIRECT was supported by Cancer Research UK (C61296/A29423). PROCAS was supported by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research programme (reference number RP-PG-0707-10031: 'Improvement in risk prediction, early detection and prevention of breast cancer' and the Prevent Breast Cancer (references GA10-033 and GA13-006).

    • Competing interests DGE has received consultancy fees from Everything Genetic Ltd.

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

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