Workshop 1: Taking a family history & drawing a family pedigree

Make sure that you complete the RM Partners online training OPTION 2 Colorectal cancer MDT: Link to training Link to supporting documents Other online courses: Taking and Drawing a Genetic Family History Use the family history worksheet to practice. Start your clinic set-up process Start your clinic set-up request now: This can take up to 3 months (sometimes more). Is there a specific system to receive germline genetic results in your region? Do you have to set-up a results portal? Ask your regional Lynch syndrome nurse.

Workshop 2: Confidentiality & Ethics

Confidentiality in Genomics See “Consent and confidentiality in genomic medicine” document by the Royal of Physicians: Most of the confidentiality points discussed in this booklet refer to predictive genetic testing but it is recommended that you read point 4.2 and case studies. Save it in a safe place as a reference document. Ethics This will be discussed by the Regional Lynch syndrome Nurses through a presentation They will help you identify when ethical situations arise, generally related to “non-disclosure” of information within the family. Main message: There are several forums to discuss ethical issues in Genomics. You can start by discussing in MDT, document, and highlight to clinical genetics or specialised services so they can deal with them.

Workshop 3: The Consultation (Part 1)

As part of your tutorials you will be able to see a full consultation by one of the Regional Lynch syndrome nurses. After, discuss the consultation and break it down into sections. This is so its easier for you select an agenda when you have your consultation and know the essentials that need to be covered. The consultation will follow the structure of this flowchart. The information that you need to discuss is covered in the RM Partner's information leaflet for patients with Endometrial Cancer To find your own way to explain Lynch syndrome, read the RM Partners’ patient information webpage as it’s easy to understand, and uses a language patients will be able to understand as well (Reviewed carefully by Lynch syndrome UK) Save all the documents available through this training in a folder where you can find them easily as you will need them later.

Workshop 3: The Consultation (Part 2)

Please, watch these recommended videos that will help you find your own style to have your genetic counselling consultation: To see how others explain the 3 possible results of genetic testing watch these short videos (max. 2.5 minutes). They will give you ideas about how you would like to explain this yourself Other short related videos available through the genomics education programme To understand how are genetic variants classified What is a genome video Autosomal dominant inheritance How is genomics used in cancer?

Workshop 4: Consultation in action: finding your style

The consultation in sections: finding your own style Write down how would you like to explain each section of the consultation. Send it over your Lynch syndrome nurse for feedback before or after practising the different sections of the consultation Exercise: think about what you would cover during your consultation in these scenarios 1st scenario: Maria has been diagnosed with endometrial cancer at 42. Her tumour sample IHC result showed loss of PMS2. She had a successful surgery and she is well. She works in genetics so you don’t need to teach your patient about genetics. • How would you explain Lynch syndrome? • How would you go through the 3 possible results? 2nd scenario: Jennifer has been diagnosed with colorectal and endometrial cancers by the age of 36y. She had surgery but the cancer has metastasized to her liver and kidneys. She is going to have palliative chemo but she hasn’t got a start date yet. She hasn’t finished school and used to work in McDonalds, but due to her illness she is unemployed now. She would like to go back to work and study to finish her A levels. McDonalds can sponsor her for her A levels course. Her IHC show loss of MSH6. She is not very familiar with what DNA is but some understanding from the Media. She looks depressed. • Would you go through what DNA is? • How would you explain Lynch syndrome? • How would you explain the 3 possible results? • Do you need to consider her emotional wellbeing?

Workshop 5: Full consultation & final documents

Full consultation: Today you will have the opportunity to practice your full consultation You will practice with your regional Lynch syndrome nurse using your own style which you developed and have already written down Go through these documents A couple of documents to save and that you might find helpful before you start your clinic Family history questionnaire Example of mainstreaming letter Make sure that you have your regions: Record of discussion form Germline genetic testing blood request form Your SOP has been approved by your team, cancer alliance representative, and clinical genetics department.

Workshop 6: Clinic set-up

Activities for clinic set up should start alongside Workshop 1 as it can be tenthly process (3 months on average). Your regional Lynch syndrome nurse and cancer alliance can provide support for this.

Educational resources for healthcare professionals

Genomics overview

Genomics is the study of an organism’s genome – its genetic material – and how that information is applied. All living things, from single-celled bacteria, to multi-cellular plants, animals and humans, have a genome – and ours is made up of DNA.

Training resources

The following training resources are available:

Genomics Education Programme:

North Thames Genomic Laboratory Hub:

South East Genomic Medicine Service Alliance:

Miscellaneous

Learning and Development Hub

Macmillan Fuse Learning Hub (login required)

Counselling and consent

Checklist

Has the patient had enough information and time to consider testing and its consequences?
Have the conversation and consent form been documented, recorded and stored according to local policy? Always document consultation as a written letter to the patient and sharing correspondence with the GP.
Has the patient been provided with:
- Record of Discussion Form to sign (this is the consent form: one copy for patient, one for notes)
- Patient information leaflets
- Contact details of the clinical team
- GMS test request form (if using phlebotomy services for blood sampling)
Has the patient been informed of logistical procedures including:
- How the test will be conducted
- When and how to expect results
- How to access support whilst waiting for results

Results key points to cover

Endometrial Cancer Testing

Negative: No pathogenic variant detected.

No onward referral to Clinical Genetics needed unless:
- There is a significant family history of breast/ovarian/prostate/pancreatic cancers
- Age at presentation is very young (<30yrs)
- Personal history of multiple cancers
May need emotional support and reassurance
Send generic letter with further details.

Positive: A pathogenic variant is detected in one of the genes on the R210 panel.

Add to MDT for further management discussion:
- Risk reducing surgery
- Surveillance
- Chemoprophylaxis management
- Lifestyle advice
- Colorectal services
Onward referral to Clinical Genetics required:
- They will arrange cascade testing and provide support for ‘To Whom it May Concern’ Letters to relatives.
- Inform patients that relatives will need to contact their local GPs for a referral to their nearest regional genetics team.
Send generic letter with further details + document in patient’s notes/EPR.

Variant of Uncertain Significance (VUS): A variant is detected in one of the genes in R210 panel, but there isn’t enough clinical evidence to link it to cancer yet.

These variants may be ‘reclassified’ in the future with more clinical data.
Onward referral to Clinical Genetics required
Send generic letter with further details + document in patient’s notes/EPR.

Ovarian Cancer Testing Results

Negative: No pathogenic variant detected.

No onward referral to Clinical Genetics needed unless:
- There is a significant family history of breast/ovarian/prostate/pancreatic cancers
- Age at presentation is very young (<30yrs)
- Personal history of multiple cancers
May need emotional support and reassurance
Send generic letter with further details.

SOMATIC only: Positive A pathogenic variant is detected in the tumour tissue sample.

Consider increased Surveillance
No onward referral to Clinical Genetics required unless:
- There is a significant family history of breast/ovarian/prostate/pancreatic cancers
- Age at presentation is very young (<30yrs)
- Personal history of multiple cancers
Send generic letter with further details + document in patient’s notes/EPR.

GERMLINE: Positive A pathogenic variant is detected in one of the genes in R207 panel.

Add to MDT for further management discussion:
- Risk reducing surgery
- Surveillance
- Chemoprophylaxis management
- Consider referral to other clinical specialties depending on the gene (ie Breast team for a BRCA1/BRCA2/PALB2/RAD51C/R AD51D variant)
Onward referral to Clinical Genetics required
- They will arrange cascade testing and provide support for ‘To Whom it May Concern’ Letters to relatives.
- Inform patients that relatives will need to contact their local GPs for a referral to their nearest regional genetics team.
Send generic letter with further details + document in patient’s notes/EPR.

Variant of uncertain Significance (VUS): A variant is detected in one of the genes in the tested panel, but there isn’t enough clinical evidence to link it to cancer yet.

These variants may be ‘reclassified’ in the future with more clinical data.
Onward referral to Clinical Genetics required

Send generic letter with further details + document in patient’s notes/EPR.

Frequently asked questions

What is 'Mainstreaming'?

Mainstreaming Genomic testing means delivering a genetic test for breast cancer patients who meet the standardised criteria set out in the National Genomic Test Directory. This is a simple blood test that can be ordered by the Breast Cancer Team instead of being outsourced/referred onto an external clinical genetics team.

The test looks for a ‘Germline’ change in the patient’s DNA sample that might be a contributing factor to their cancer diagnosis.

The results of the test are ‘actioned’ by the breast team, which include referring the patient to clinical genetics if it is necessary (see ‘How do I and when do I need to refer to Genetics Services?’ FAQ below).
Why do we need 'Mainstreaming'?

Testing within the breast cancer team speeds up results, reduces the number of healthcare professionals the patient has to interact with and hospital appointments they have to navigate during a stressful time. It ensures the patient can access relevant treatment in a timely manner based on their results.

The patient will be offered counselling and consent for this blood test in the days after their diagnosis (vs seeing genetics in many places this is a waiting list of more than 3 months).
Germline mutations are inherited genetic changes that are present in the DNA of every cell in the body, including sperm and egg cells. These mutations can be passed down from generation to generation and can increase the risk of developing certain diseases, including cancer.

Somatic mutations, on the other hand, are genetic changes that occur in non germline cells during a person's lifetime. These mutations are not present in every cell of the body and cannot be passed down to offspring. Somatic mutations can occur due to a variety of factors, including exposure to environmental toxins, aging, and errors that occur during DNA replication.
How will the results of a positive test in the R207 (Ovarian) Panel affect treatment?
Targeted therapies:

Established biomarker of PARPi responsiveness

Denosumab

Indicative of sensitivity to DNA-damaging chemotherapies, including anthracyclines.

Surgeries:

Informs risk-reducing surgery: bilateral mastectomy.

Surveillance:

MRI

Mammogram (NHS Breast Screening Programme Guidelines: https://www.gov.uk/government/publications/breast-screening-higher-risk-women-surveillanceprotocols/tests-and-frequency-of-testing-for-women-at-very-high-risk--2

Chemoprophylaxis:

Tamoxifen, Raloxifene.
How will the results of a positive test for Lynch Syndrome (R210 panel) affect treatment?
Targeted therapies & chemoprophylaxis:

Aspirin: (NICE guidelines 2020) between the ages of 25- 65 years. Aspirin has been shown to reduce the long term risk of cancer in Lynch syndrome by around 50%. Trials to determine the best dose of aspirin for cancer prevention are still ongoing. Patients need to discuss with their GP whether you have any contraindications to taking aspirin. Patients younger than 25 who wish to start taking aspirin should with their medical team. [Lynch syndrome: should I take aspirin to reduce my risk of getting bowel cancer. Patient decision aid, NICE, 2020] To find out the latest information and recommendations in aspirin, you can visit the CAPP3 trial website

Immunotherapy.

Risk reducing surgeries:

Hysterectomy & Bilateral Salpingo-Oophorectomy: Women who have completed their family may consider risk-reducing surgery to remove the uterus, fallopian tubes +/- ovaries, after the age of 35. Hormone replacement therapy is usually recommended after risk-reducing bilateral Salpingo-Oophorectomy to offset negative impact of premature menopause, up until the time at which natural menopause would be expected to occur.

Surveillance:

2 yearly colonoscopy

MLH1 and MSH2 gene carriers: start at 25 years old

MSH6 and PMS2 gene carriers: start at 35 years old (BSG Guidelines 2019).

Lifestyle advice to reduce the risk of colorectal cancer:

Losing weight can reduce the risk of early onset colorectal cancer by half.

Stopping smoking.

Dietary advice: High fibre, low fat, with plenty of fruit and vegetables. Try to eat less red and processed meat. It is also good for your general health that you include starchy foods in your diet such as plantains and green bananas [CAPP2 evidence on resistant starch]

One-off screening for Helicobacter pylori: H. pylori is a bacteria that 30% of the population have in the stomach. Eradication of these bacteria may reduce the lifetime risk of gastric cancer by up to half. To arrange testing for this contact your GP. This is recommended before commencing aspirin chemoprophylaxis.

Symptom Awareness: Prompt investigation of any symptoms (gynaecological, urinary, gastrointestinal, dermatological and so on). [HEE, Knowledge Hub: Lynch, 2022]
Lynch Syndrome: How do I and when do I need to refer to Genetics Services?
Always following results: Discuss your results in the result forum allocated to you by your Lynch syndrome nurse for safety netting to discuss recommendations for your patients, which will include: cancer prevention programme and surveillance recommendations if VUS or negative.

Refer to local clinical genetics team, usually using a standardised form via email that will be accessible via your nearest Genomics Laboratory Hub website. Enclose the following in your referral.

Checklist:

Attach histopathology reports

Attach minutes from cancer MDT meeting

Attach family pedigree

Call and inform patient they will receive an appointment for genetic referral.

If the result is Negative or VUS the case might be virtually reviewed and your patient might not receive an appointment. You will find out when you discuss your result in your results forum.
How do I and when do I need to refer to Genetics Services?
A patient should be referred to Genetics Services when:

When patient has a positively identified pathogenic variant

When a patient has a variant of uncertain significance (VUS)

When a patient has a significant family history

When you are not sure.

Refer to local clinical genetics team, usually using a standardised form via email that will be accessible via your nearest Genomics Laboratory Hub website.
How do I calculate a patient’s risk?

Consider using validated tools recommended and developed by genetics services such as:

- CanRisk

- QGenome

- Manchester Score

- Ovarian Cancer Action Risk Calculator: Explore Your Risk with the Hereditary Cancer Risk Tool | Ovarian Cancer Action

Resources and reading list

Miscellaneous

Hereditary Hub | Ovarian Cancer Action
Hereditary Cancer Risk Tool: Explore Your Risk with the Hereditary Cancer Risk Tool | Ovarian Cancer Action

Podcasts

Webinars and lectures

Preventing Cancer in Jewish Communities | Ovarian Cancer Action
Genetics and targeted therapies in ovarian cancer | Target Ovarian Cancer (register for free with the ‘Nurses Network’ to access)
Harnessing the Power of Clinical Nurse Specialists in the Roll Out of Genomics | East Genomics
DNA Graffiti: The Francis Crick Lecture 2022, Professor Serena Nik-Zainal | The Royal Society
Advances in Clinical Genomics (3 webinars) | Front Line Genomics
Royal Society of Medicine Live with Professor Dame Lesley Fallowfield | RSM
What Are BRCA Gene Mutations? | Ovarian Cancer Action
From Niche to Necessity, Mainstreaming BRCA+ Testing | Macmillan Cancer Support

Videos

Why is your BRCA alteration status important to know if you have ovarian cancer? - Youtube | Eve Appeal

Posters

Further resources

Reading list

Calzone, K. A., Kirk, M., Tonkin, E., Badzek , L., Benjamin, C., & Middleton, A. (2018). The global landscape of nursing and genomics. Journal of Nursing Scholarship, 3), 249 256 https://doi.org/10.1111/jnu.12380
Coulson J. (2022). ‘Understanding the role of genomics in nursing practice.’ Nursing standard (Royal College of Nursing (Great Britain) Britain), 10.7748/ns.2022.e12053. Advance online publication. https://doi.org/10.7748/ns.2022.e12053
Cuthill, V. (2023), ‘Demystifying Genomics in Cancer Care’, Macmillan Cancer Support. Available at: Demystifying genomics in cancer care | Macmillan Cancer Support
Georgiou, D., Monje Garcia, L., Miles, T., Monahan, K., Ryan, N. (2023) ‘A Focused Clinical Review of Lynch Syndrome’, Cancer Management and Research , 15 (67 85), doi:10.2147/CMAR.S283668
Hanson, H., Kulkarni, A., Loong, L., Kavanaugh, G. et al. (2022) ‘UK consensus recommendations of cancer risk for women with germline pathogenic variants in cancer predisposition genes: RAD51C, RAD51D, BRIP1 and PALB2 .’ Journal of Medical Genetics, BMJ . 0: 1 13. doi : https://doi.org/10.1136/jmg 2022 108898
Launer , J. (2021)’Effective Clinical Conversations: The Art of Curiosity’ Postgrad Med J , 97, pp 339 340. DOI: Effective clinical conversations: the art of curiosity (bmj.com)
NHS England, (2022) ‘Accelerating genomic medicine in the NHS’, NHS England. Available at: NHS England » Accelerating genomic medicine in the NHS
Patch, C. & Middleton, A. (2018) ‘Genetic counselling in the era of genomic medicine’, British Medical Bulletin , 126(1), 27 36. DOI: https://doi.org/10.1093/bmb/ldy008
Pichini, A & Bishop, M. (2022) ‘A nationally agreed cross professional competency framework to facilitate genomic testing’ Genetics in Medicine. 24(8), 1743 1752. DOI: https://doi.org/10.1016/j.gim.2022.04.023
Ryan, NAJ., et al (2019) ‘The proportion of endometrial cancers associated with Lynch Syndrome: a systematic review of the literature and meta analysis.’ Genetics in Medicine. 21 (10), 2167 2180. DOI: https://doi.org/10.1038/s41436 019 0536 8
Sobocan, M., Chandrasekaran, D., Sideris, M. et al. (2023) “Patient decision aids in mainstreaming genetic testing for women with ovarian cancer: A prospective cohort study” British Journal of Obstetrics and Gynaecology , 00:1 10. Accessible at: DOI: 10.1111/1471 0528.17675
Yang, Xin et al. “Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 38,7 (2020): 674 685. doi:10.1200/JCO.19.01907

Useful information

Genomics Education Programme: Competency framework for consent
Gene risk level table:

A table showing the risk level of certain genes.

Workshops

Lynch syndrome mainstreaming training programme

Developed by Laura Monje-Garcia, National Lead Nurse for the Lynch syndrome project.

The programme is made up of 6 2-hour workshops delivered as part of the mainstreaming training for Lynch syndrome.

The Lynch syndrome mainstreaming training programme uses the Health Education England (HEE) Genomic Education Programme (GEP) competency frameworks:

“Facilitating genomic testing competencies”: It covers “informed consent”. You will go through all the points during the workshops, but if you are not sure about something, ask your regional Lynch syndrome nurse. This is a reference document and is not intended to be used as an assessment tool.
“Communicating germline genomics results: A competency framework”: This is a reference document and is not intended to be used as an assessment tool.