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A pilot study investigating feasibility of mainstreaming germline BRCA1 and BRCA2 testing in high-risk patients with breast and/or ovarian cancer in three tertiary Cancer Centres in Ireland

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Abstract

In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient’s BRCA status. “Mainstreaming” BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the UK and internationally. We aimed to pilot this pathway in three Irish tertiary centres. A service evaluation project was undertaken over a 6-month period between January and July 2017. Eligible patients, fulfilling pathology and age-based inclusion criteria defined by TGL clinical, were identified, and offered constitutional BRCA1/BRCA2 testing after pre-test counselling by treating clinicians. Tests were undertaken by TGL Clinical. Results were returned to clinicians by secure email. Onward referrals of patients with uncertain/pathogenic results, or suspicious family histories, to Clinical Genetics were made by the treating team. Surveys assessing patient and clinician satisfaction were sent to participating clinicians and a sample of participating patients. Data was collected with respect to diagnostic yield, turnaround time, onward referral rates, and patient and clinician feedback. A total of 101  patients underwent diagnostic germline BRCA1/BRCA2 tests through this pathway. Pathogenic variants were identified in 12 patients (12%). All patients in whom variants were identified were appropriately referred to Clinical Genetics. At least 12 additional patients with uninformative BRCA1/BRCA2 tests were also referred for formal assessment by Clinical Geneticist or Genetic Counsellor. Issues were noted in terms of time pressures and communication of results to patients. Results from a representative sample of participants completing the satisfaction survey indicated that the pathway was acceptable to patients and clinicians. Mainstreaming of constitutional BRCA1/BRCA2 testing guided by age- and pathology-based criteria is potentially feasible for patients with breast cancer as well as patients with ovarian cancer in Ireland.

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Abbreviations

BC:

Breast cancer

CNS:

Clinical nurse specialist

ER:

oEstrogen receptor

HGSOC:

High grade serous ovarian cancer

KPI:

Key performance indicator

LGSOC:

Low grade serous ovarian cancer

OC:

Ovarian cancer

PR:

Progesterone receptor

PV:

Pathogenic variant (mutation)

RMH:

The Royal Marsden NHS Foundation Trust

TNBC:

Triple Negative Breast Cancer

VUS:

Variant of Uncertain Significance

VRE:

Variant Requiring Evaluation

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Acknowledgements

With thanks to Ms Judith McLucas, Ms Caoimhe Ní Mhuircheartaigh and Dr Oliver O’Brien for their assistance. MCG-Ireland Collaborators: Terri P. McVeigh, Angela J. George, Simon Ward, (Royal Marsden NHS Trust), Ann Strydom, Sheila Seal, Nazneen Rahman, (TGL Clinical Laboratory), Una M. McVeigh, Karl J. Sweeney, Ray McLaughlin, Carmel Malone, Michael J. Kerin, Kevin Barry, Michael Sugrue, Geraldine MacGregor, Pauline McGough, Judith McLucas, Margaret Rushe, Maccon Keane, Paul Donnellan, Ala Yousif, Michael O’Leary, Katherine Astbury, Joanne Higgins, Caoimhe Ní Mhuircheartaigh, (Soalta University Hospital Group), David J. Gallagher, Eileen Berkeley, Carmel Nolan, Elizabeth Connolly, Terry Boyle, Dhafir Al-Azawi, Elaine Richardson, Samantha Doyle, (St James’s University Hospital), Claire Giffney, Donal Brennan, Ruaidhri McVey, Thomas Walsh, Oliver O’Brien, Sheila Broderick, (Mater Misericordiae University Hospital), Michael Farrell, (Mater Private Hospital).

Funding

This pilot was supported by the Royal Marsden/ICR NIHR Specialist Biomedical Research Centre for Cancer and Wellcome grant 098518, and Health Research Board grants HRB/HSE NSAFP 2014/1 and HRB KEDS-2017-043. Constitutional genetic tests were funded by TGLclinical.

Author information

Authors and Affiliations

  1. Cancer Genetics Unit, Royal Marsden NHS Foundation Trust, London, UK

    Terri Patricia McVeigh, Simon Ward & Angela J. George

  2. Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK

    Terri Patricia McVeigh & Angela J. George

  3. Saolta Health Care Group, Galway University Hospital, Galway, Ireland

    Karl J. Sweeney, Katherine Astbury, Paul Donnellan, Joanne Higgins, Maccon Keane, Michael J. Kerin, Carmel Malone, Pauline McGough, Ray McLaughlin, Michael O’Leary & Margaret Rushe

  4. Mater Misericordiae University Hospital, Dublin, Ireland

    Donal J. Brennan, Sheila Broderick, William Boyd, Ruaidhri McVey & Thomas Walsh

  5. National University of Ireland, Galway, Ireland

    Una M. McVeigh, Michael J. Kerin & Carmel Malone

  6. TGL Clinical Laboratory, Sutton, UK

    Ann Strydom, Sheila Seal & Nazneen Rahman

  7. Saolta Health Care Group, Mayo University Hospital, Co Mayo, Castlebar, Ireland

    Michael Kevin Barry

  8. Saolta University Health Care Group, Letterkenny University Hospital, Co Donegal, Letterkenny, Ireland

    Geraldine MacGregor & Michael Sugrue

  9. Saolta University Hospital Group, Sligo University Hospital, Sligo, Ireland

    Ala Yousif

  10. St James’s University Hospital, Dublin, Ireland

    Dhafir Al-Azawi, Eileen Berkeley, Terence J. Boyle, Elizabeth M. Connolly, Carmel Nolan, Elaine Richardson & David J. Gallagher

  11. Children’s Health Ireland at Crumlin, Dublin, Ireland

    Claire Giffney

  12. The National Maternity Hospital, Holles St, Dublin, Ireland

    Donal J. Brennan & Samantha B. Doyle

  13. Mater Private Hospital, Dublin, Ireland

    Michael Farrell & David J. Gallagher

Authors
  1. Terri Patricia McVeigh
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  2. Karl J. Sweeney
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  3. Donal J. Brennan
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  4. Una M. McVeigh
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  5. Simon Ward
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  6. Ann Strydom
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  7. Sheila Seal
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  8. Katherine Astbury
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  9. Paul Donnellan
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  10. Joanne Higgins
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  11. Maccon Keane
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  12. Michael J. Kerin
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  13. Carmel Malone
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  14. Pauline McGough
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  15. Ray McLaughlin
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  16. Michael O’Leary
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  17. Margaret Rushe
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  18. Michael Kevin Barry
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  19. Geraldine MacGregor
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  20. Michael Sugrue
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  21. Ala Yousif
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  22. Dhafir Al-Azawi
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  23. Eileen Berkeley
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  24. Terence J. Boyle
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  25. Elizabeth M. Connolly
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  26. Carmel Nolan
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  27. Elaine Richardson
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  28. Claire Giffney
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  29. Samantha B. Doyle
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  30. Sheila Broderick
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  31. William Boyd
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  32. Ruaidhri McVey
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  33. Thomas Walsh
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  34. Michael Farrell
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  35. David J. Gallagher
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  36. Nazneen Rahman
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  37. Angela J. George
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Corresponding author

Correspondence to Terri Patricia McVeigh.

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Conflict of interest

Dr Nazneen Rahman is a Non-executive Director of AstraZeneca.

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McVeigh, T.P., Sweeney, K.J., Brennan, D.J. et al. A pilot study investigating feasibility of mainstreaming germline BRCA1 and BRCA2 testing in high-risk patients with breast and/or ovarian cancer in three tertiary Cancer Centres in Ireland. Familial Cancer 22, 135–149 (2023). https://doi.org/10.1007/s10689-022-00313-0

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