Protocols for the Surveillance of Women at Higher Risk of Developing Breast Cancer

Overview

This specialist Guidelines summary covers the surveillance of women at higher risk of developing breast cancer. It is aimed at secondary care oncology teams. It does not include recommendations on screening tests or short-term recalls. For further information, refer to the full guideline.

Accessing Very High-Risk Screening

• Oncologists wishing to refer women who received radiotherapy to sites involving breast tissue for cancers other than lymphoma, are advised to complete a breast screening after radiotherapy dataset (BARD) non-lymphoma patient referral-form and send to BARD on chn-tr.bard@nhs.net  to confirm eligibility for very high risk screening, and subsequent referral if appropriate
• Referrers should make sure that all women referred meet the criteria for very high-risk screening within the NHS breast screening programme (BSP) and include all required evidence.

Referrals by Clinical Genetics Services or Oncology Centres

• Women who meet the very high-risk criteria should be referred to their local breast screening service
• Completed referral forms should be sent to a nominated generic email address for the appropriate breast screening service
• Referrals should contain all the necessary information to demonstrate the individual meets the very high-risk criteria and referrals must only be accepted using a breast screening referral form for women at very high risk with sufficient supporting evidence as required.

Threshold for Screening Women in the Very High-Risk Programme

• The NHS BSP screens women at very high risk of breast cancer due to:
  • a proven germline pathogenic variant in BRCA1, BRCA2, TP53, A-T homozygotes, PALB2, PTEN, STK11 or CDH1, or any other high-risk gene based on testing in a clinically accredited laboratory
  • having received radiotherapy to breast tissue during treatment for Hodgkin and non-Hodgkin lymphoma
    • note: younger women treated with radiotherapy due to breast cancer (under 50) are excluded from the NHS BSP very high-risk programme
• The NICE familial breast cancer guideline categorises women at increased risk of breast cancer into moderate- or high-risk categories
• Only a subset of those defined by NICE as being at high risk reach the very high-risk group threshold used in the NHS BSP. This has previously been set at 8 times the relative risk of women in the general population
• To differentiate between the NICE and NHS BSP guidance, very high risk is defined by the NHS BSP as:
  • women with a lifetime risk of 40% or greater due to a specific genetic abnormality in the woman or her family
  • those receiving radiotherapy to breast tissue during treatment for Hodgkin and non-Hodgkin lymphoma between the ages of 10 and 35 years
  • a small number of women who received radiotherapy to breast tissue during treatment for cancers other than lymphoma.

How to Calculate Women at Very High Risk

• A woman is considered to be at very high risk if she has a test result that identifies a germline pathogenic variant in a gene that would confer a 40–95% lifetime risk of breast cancer
• Some women may choose not to have genetic testing. In order to avoid a situation where a woman with a known pathogenic variant in her family is obliged to proceed with predictive genetic testing to access very high-risk screening, the following risk assessment process will apply:
  • if a woman has not been tested but has a first-degree relative with a germline BRCA1, BRCA2, or TP53 pathogenic variant, she has a 50% chance of carrying this variant. As a result, she will be eligible for very high-risk screening from age 30 up to and including the age of 50. For such a woman to be eligible for very high-risk screening when aged between 25 and 29 years, she should have an 8% 10-year risk confirmed by an NHS clinical genetics service
  • to access this, confirmation is required from the genetics service that a first-degree relative carries a germline pathogenic variant. After the age of 50, a previously untested woman will be returned to the routine screening programme
• After the age of 50, a personal test result identifying a pathogenic variant is required to continue to access the very high-risk programme, as the residual lifetime risk associated with a pathogenic variant will have reduced by this time. A woman with only a 50% chance of carrying this pathogenic variant would no longer reach the 40% lifetime risk threshold to access very high-risk screening.

How to Decide Lifetime Risk in the Absence of a Genetic Test

• Risk assessment completed by the NHS clinical genetics service must provide clear confirmation of the level of risk using an NHS endorsed computer risk modelling software program, BOADICEA (CanRisk) or Tyrer Cuzick. The 10-year risk estimate must be submitted with the referral proforma as evidence that the woman satisfies the appropriate risk at time of screening entry.

• A small proportion of women at very high genetic risk will meet the 8% threshold for screening earlier than 30 years of age
• Assess 10-year risk for each year between 25 and 29 years to determine at what age the risk meets the 8% threshold and hence age at entry to screening
• A woman should have an 8% 10-year risk confirmed by an NHS clinical genetics service (required by the NHS BSP). This is required for all equivalent risk categories.

• The 10-year risk at age 30 should be determined by an NHS clinical genetics service (required by the NHS BSP) and screening requested if an 8% 10-year risk is confirmed
• This additional evidence is required for all equivalent risk categories except where a first-degree relative with a BRCA1, BRCA2, or TP53 pathogenic variant has been confirmed.

• The 10-year screening risk at age 40 should be determined by an NHS clinical genetics service (required by the NHS BSP) and screening requested if a 12% 10-year risk is confirmed
• This additional evidence is required for all equivalent risk categories except where a first-degree relative with a BRCA1, BRCA2, or TP53 pathogenic variant has been confirmed.

Women with Proven Pathogenic Variants in High-Risk Genes

• Referrals for women aged 30 and above with a proven germline BRCA1/2 or PALB2 pathogenic variant can be automatically accepted into the very high-risk programme, with supporting evidence
• Referrals for BRCA1, BRCA2 gene, and PALB2 carriers aged between 25 and 29 years must include evidence of risk, using an NHS endorsed computer risk modelling software program as detailed above, to be accepted into the very high-risk programme
• Surveillance starts at 20 years for TP53, at 25 years for A-T homozygotes, and at 30 years for PTEN, STK11, and CDH1
• Evidence is required from the NHS clinical genetics service confirming the presence of a pathogenic variant and stating the name of the gene.

Women Previously Treated with Total Body Irradiation

• Women who have previously received total body irradiation are at an elevated risk of breast cancer in the years following treatment
• However, there is insufficient evidence to show that the risk reaches the threshold to qualify this cohort of women for screening in the very high-risk programme.

Queries Over Entitlement Following Previous Radiotherapy

• Most women who have had radiotherapy fields involving breast tissue at a young age are those receiving treatment for Hodgkin or non-Hodgkin lymphoma. However, other diagnoses may also result in similar radiotherapy treatment fields
• If a woman had radiotherapy involving breast tissue below the age of 36 years but it is unclear if she is eligible for very high-risk screening within the NHS BSP, contact BARD for advice on chn-tr.bard@nhs.net.

When Very High-Risk Screening Stops

• A woman at very high risk should continue to be invited for screening up to her 71st birthday or up to the age of 50 where she is determined to be at an equivalent, but untested, risk level
• When a woman reaches 71 years of age, routine invitations for very high-risk screening will stop. At this stage she is entitled to self-refer for screening. For women in the very high-risk programme, this will be annual screening in accordance with her VHR screening protocol. At this point, if her breast density score is not BI-RADS A, screening should continue to include magnetic resonance imaging (MRI) and mammography and be subject to annual review
• Eligible women over the age of 70 should be informed that they need to contact their local screening service each year to arrange annual screening.

Screening Women in Pregnancy and Lactation

• Screening with mammography can be safely performed during pregnancy, but as mammographic density increases during pregnancy and lactation, its effectiveness is reduced
• Women can be screened during lactation, but are advised to breastfeed or express milk prior to the examination
• Shielding is not considered necessary due to the low radiation dose of mammography
• MRI during pregnancy is not recommended due to the high level of background parenchymal enhancement during pregnancy and lactation. However, each woman should be reviewed and Royal College of Radiologists symptomatic breast screening imaging guidance covering imaging surveillance in pregnancy and lactation should be followed
• If women opt to postpone screening due to pregnancy or lactation, MRI screening should resume 3 months both postpartum and following cessation of lactation.

Screening Transgender People

• Transgender (trans) men and non-binary people who have breast tissue and fulfil the criteria to be eligible for very high-risk screening will be invited for screening if they are registered with a GP with a gender marker of female or indeterminate
• If they are registered with a gender marker of male, they will not be automatically invited. They will need to speak to their GP who can arrange for a referral to a local hospital for the appropriate screening on an annual basis
• People identifying as trans women who have breast tissue and are registered as a female and who are eligible for very high-risk screening will be invited for screening.