Genomics Toolkit: Breast

These are the mainstreaming R215 panel inclusion criteria for CDH1-related cancer syndrome.

If a patient presents with one of the following, they are eligible for R215 panel testing.

• Diffuse gastric cancer; under the age of 50 years.
• Gastric in situ signet ring cells or pagetoid spread of signet ring cells under 50 years.
• Diffuse gastric cancer at any age with a personal history or first degree relative with cleft lip or cleft palate.
• Double primary diffuse gastric cancer and lobular breast cancer; both under 70 years.
• Diffuse gastric cancer and 1 or more first degree /second degree relatives with diffuse gastric cancer at any age.
• Diffuse gastric cancer at any age and 1 or more first degree relative / second degree relative with lobular breast cancer under 70 years
• Lobular breast cancer and 1 or more first degree relative / second degree relative with diffuse gastric cancer (1 or more case occurred under 70 years).
• 2 cases of lobular breast cancer under 50 years e.g. bilateral or multiple ipsilateral tumours
• Bilateral lobular breast cancer under 70 years
• Diffuse gastric cancer in any individual of Maori ethnicity

Deceased affected individual (proband) where (i) the individual +/- family history meets one of the above criteria, (ii) appropriate tissue is available (tumour or normal), and (iii) no living affected individual is available for genetic testing.

NOTE: At least one cancer should be histologically confirmed

Genetic testing may occasionally be appropriate outside these criteria following discussion at a specialist MDT with a cancer geneticist present.

Referrals for testing will be triaged by the Genomic Laboratory; testing should be targeted at those where a genetic or genomic diagnosis will guide management for the proband or family.

Where in the pathway?

Requesting Specialties

• Clinical Genetics
• Gastroenterology
• Surgery*

*Surgery to cover upper gastro-intestinal surgeons

Associated tests

Please refer to the National Genomic Test Directory for inclusion criteria and further information.

These are the mainstreaming R208 panel inclusion criteria for inherited breast cancer and ovarian cancer: If a patient presents with one of the following, they are eligible for R208 panel testing.

1. A patient with breast* or high grade ovarian cancer where the individual +/- family history meets one of the criteria.  

• Breast cancer, age under 40 years, OR
• Bilateral breast cancer, age under 60 years, OR
• Triple negative breast cancer, age under 60 years, OR
• Assigned male at birth and affected with breast cancer any age, OR
• Breast cancer, age under 45 years and a first degree relative with breast cancer age under 45 years, OR
• Combined pathology-adjusted Manchester score higher than 15 or single gene pathology adjusted score of higher than 10 or BOADICEA/CanRisk score higher than 10%, OR
• Ashkenazi Jewish ancestry and breast cancer at any age, OR
• 1 or more grandparent from Westray (Orkney) or Whalsay (Shetland) and breast cancer at any age.

2. A  patient with pancreatic cancer AND family history of breast*/high grade ovarian/prostate cancer with a pathology adjusted Manchester score of higher than 15/CanRisk score of 10%.

3. A patient with prostate cancer AND a family history of breast/ovarian/pancreatic cancer with a pathology adjusted Manchester score of higher than 15/CanRisk score of 10%.

4. Deceased patient with breast* or high grade ovarian cancer with:

• A stored DNA, blood or tissue sample available for DNA extraction, AND
• Pathology-adjusted Manchester score higher than 17 or CanRisk score higher than 15%, AND
• No living affected individual is available for genetic testing.

5. A patient with:

• first degree relative affected by breast* or serous ovarian cancer, AND
• Combined pathology-adjusted Manchester score higher than 20 or BOADICEA/CanRisk score of higher than 20% for affected relative or BOADICEA/CanRisk score of higher than 10% for unaffected relative AND
• No living affected individual is available for genetic testing, AND
• No deceased affected individual with tumour material available for testing.

Note for living patients:

Where more than one family member may be eligible for unaffected testing, the residual probability of a causative pathogenic variant in the family should be considered, taking into account prior normal unaffected tests.

NOTE:

• *Breast cancer definition includes high grade DCIS
• The proband's cancer and majority of reported cancers in the family should have been confirmed.
• The pathology adjusted Manchester score involved incorporation of pathology data for the tested proband alone, i.e. pathology need not be sought for other family members.
• Ovarian cancer: Fallopian Tube and Primary Peritoneal cancers can be included
• BRCA1/BRCA2 testing should not typically have previously been performed. Exceptions may include, for example, patients who have been tested through the Jewish Community’s NHS BRCA-Testing Programme for BRCA1/BRCA2 and not received a molecular diagnosis
• Testing of unaffected and deceased individuals can only be offered by Clinical Genetics Genetic testing may occasionally be appropriate outside these criteria following discussion at a specialist MDT with a cancer geneticist present

Overlapping indications

• M2 Ovarian carcinoma should be used for somatic testing
• M3 Breast cancer should be used for somatic testing
• R444 NICE approved PARP inhibitor treatment

Referrals for testing will be triaged by the Genomic Laboratory; testing should be targeted at those where a genetic or genomic diagnosis will guide management for the proband or family.

Where in the pathway?

At presentation

Requesting Specialties

• Oncology
• Clinical genetics
• surgery

Associated tests

Please refer to the National Genomic Test Directory for inclusion criteria and further information.

These are the R444.1 panel inclusion criteria. They are for people who do not meet the R208 or R430 criteria AND have a current cancer diagnosis.

If a patient presents with one of the following, they are eligible for testing:

R444.1 Breast Cancer

• With residual invasive disease of the breast, resected lymph nodes or both at the time of surgery.

2. Those with triple negative breast cancer who are having adjuvant chemotherapy:

• Node-positive cancer
• Node-negative cancer and a primary tumour of 2cm or greater.

3. Those with hormone-receptor positive, HER2-negative breast cancer who have received neo-adjuvant chemotherapy:

• With residual invasive disease of the breast, resected lymph nodes or both at the time of surgery AND a CPS + EG score of 3 or more based on pre-treatment clinical and post-treatment pathological stage, receptor status and histological grade. Learn more. 

4. Those with hormone-receptor positive, HER2-negative breast cancer who are having adjuvant chemotherapy:

• 4 or more pathologically confirmed positive lymph nodes.

5. For those who have HER2-negative locally advanced or metastatic breast cancer: 

• Patients should have been previously treated with an anthracycline and/or a taxane in the neo/adjuvant, locally advanced or metastatic setting unless patients were not suitable for these treatments.
• Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine-based therapy, or be considered unsuitable for endocrine-based therapy.      

R444.2 Prostate Cancer

Metastatic, castration-resistant prostate cancer where somatic tumour testing (M218.1) has failed.

Overlapping indications

• R208 Inherited breast cancer and ovarian cancer
• R430 Inherited prostate cancer
• M3 breast cancer should be used for somatic testing
• M218 prostate cancer should be used for somatic testing

Referrals for testing will be triaged by the Genomic Laboratory; testing should be targeted at those where a genetic or genomic diagnosis will guide management for the proband or family.

Where in Pathway?

At earliest stage, either at primary surgery or after neo-adjuvant chemotherapy

Requesting Specialties

• Clinical Genetics
• Surgery
• Oncology

Associated tests

Please refer to the National Genomic Test Directory for inclusion criteria and further information.

There are several other tests and inherited conditions that are related to breast cancer. These include:

• PTEN Hamartoma Tumour Syndrome (R213)
• Somatic testing for breast cancer (M3)
• Li Fraumeni Syndrome (R216)
• Inherited Pancreatic Cancer (R367)
• Inherited Prostate Cancer (R430).

The number in brackets is the National Genomic Test Directory code for the related test. Please note: M codes are found in the ‘National genomic test directory for cancer’ and the R codes are found in the ‘Rare and Inherited Disease Eligibility Criteria’.