Familial Breast Cancer in Secondary Care: Classification, Care, and Managing Breast Cancer and Related Risks in People with a Family History of Breast Cancer

This secondary care Guidelines summary covers care for people with a family history of breast, ovarian, or another related (prostate or pancreatic) cancer. It aims to improve the long-term health of these families by describing strategies to reduce the risk of and promote early detection of breast cancer. It also includes advice on treatments (tamoxifen, raloxifene) and surgery (mastectomy).

This summary only covers recommendations for secondary care and specialist settings. See the Guidelines primary care summary for recommendations relevant to primary care, or refer to the full guideline.  

Clinical Significance of a Family History of Breast Cancer

Accuracy of Family History

Family History-taking in Secondary Care

• A family history should be taken when a person with no personal history of breast cancer presents with breast symptoms or has concerns about relatives with breast cancer.
• A third-degree family history should be taken in secondary care where possible and appropriate.
• Tools such as family history questionnaires and computer packages exist that can aid accurate collection of family history information and risk assessment and they should be made available.

Family History-taking in a Specialist Genetic Clinic

• A third-degree family history should be taken in a specialist genetic clinic for a person with no personal history of breast cancer, if this has not been done previously.
• For accurate risk estimation, the following are required:
  • age of death of affected and unaffected relatives
  • current age of unaffected relatives.
• In general, it is not necessary to validate breast cancer-only histories (via medical records/cancer registry/death certificates).
• If substantial management decisions, such as risk-reducing surgery, are being considered and no mutation has been identified, clinicians should seek confirmation of breast cancer-only histories (via medical records/cancer registry/death certificates).
• Where no family history verification is possible, agreement by a multidisciplinary team should be sought before proceeding with risk-reducing surgery.
• Abdominal malignancies at young ages and possible sarcomas should be confirmed in specialist care.

Family History and Carrier Probability

• When available in secondary care, use a carrier probability calculation method with demonstrated acceptable performance (calibration and discrimination) as well as family history to determine who should be offered referral to a specialist genetic clinic. Examples of acceptable methods include BOADICEA and the Manchester scoring system.
• In a specialist genetic clinic, use a carrier probability calculation method with demonstrated acceptable performance (calibration and discrimination) to assess the probability of a BRCA1 or BRCA2 mutation. Examples of acceptable methods include BOADICEA and the Manchester scoring system.
• If there are problems with using or interpreting carrier probability calculation methods, use clinical judgement when deciding whether to offer genetic testing.

Communicating Cancer Risk and Carrier Probability

• People should be offered a personal risk estimate but information should also be given about the uncertainties of the estimation.
• When a personal risk value is requested, it should be presented in more than one way (for example, a numerical value, if calculated, and qualitative risk).
• People should be sent a written summary of their consultation in a specialist genetic clinic, which includes their personal risk information.

For details of information and support, including information provision for people with concerns about familial breast cancer risk, see the full guideline.

Care of People in Secondary Care and Specialist Genetic Clinics

Care and Management Approach in Secondary Care

• Care of people in secondary care (such as a breast care team, family history clinic or breast clinic) should be undertaken by a multidisciplinary team. It should include the following:
  • written protocols for management
  • central, standardised resources
  • mammographic surveillance available to standard of the national breast screening programmes (England – NHS Breast Screening Programme [NHSBSP]; Wales – Breast Test Wales; Northern Ireland – NI Breast Screening Programme)
  • access to surveillance
  • access to a team offering risk-reducing surgery
  • standardised written information
  • designated/lead clinicians
  • a designated contact for primary care
  • a designated contact in a specialist genetic clinic
  • audit
  • clinical trials access
  • access to psychological assessment and counselling
  • information about support groups and voluntary organisations
  • administrative support.
• People who meet the following criteria should be offered secondary care and do not require referral to a specialist genetic clinic:
  • 1 first-degree relative diagnosed with breast cancer at younger than age 40 years or
  • 2 first-degree or second-degree relatives diagnosed with breast cancer at an average age of older than 50 years or
  • 3 first-degree or second-degree relatives diagnosed with breast cancer at an average age of older than 60 years or
  • a formal risk assessment (usually carried out in a specialist genetic clinic) or a family history pattern is likely to give risks of greater than 3 to 8% risk in the next 10 years for women aged 40 years, or a lifetime risk of 17% or greater but less than 30% (a woman's age should be assumed to be 40 for a woman in her forties; a 10-year risk should be calculated for the age range 40 to 49) provided that none of the following are present in the family history:
  • bilateral breast cancer
  • male breast cancer
  • ovarian cancer
  • Jewish ancestry
  • sarcoma in a relative younger than 45 years of age
  • glioma or childhood adrenal cortical carcinomas
  • complicated patterns of multiple cancers at a young age
  • very strong paternal history (4 relatives diagnosed at younger than 60 years of age on the father's side of the family).
• People whose risk does not meet the criteria for referral to secondary care (see the section on referral from primary care in the full guideline) can be referred back to primary care:
  • with appropriate information being offered and
  • support mechanisms (for example, risk counselling, psychological counselling and risk management advice) need to be identified, and should be offered to people not eligible for referral and/or surveillance on the basis of age or risk level who have ongoing concerns.

Referral to a Specialist Genetic Clinic

• People who meet the following referral criteria should be offered a referral to a specialist genetic clinic.
  • At least the following female breast cancers only in the family:
    • 2 first-degree or second-degree relatives diagnosed with breast cancer at younger than an average age of 50 years (at least 1 must be a first-degree relative) or
    • 3 first-degree or second-degree relatives diagnosed with breast cancer at younger than an average age of 60 years (at least 1 must be a first-degree relative) or
    • 4 relatives diagnosed with breast cancer at any age (at least 1 must be a first-degree relative). or
  • Families containing 1 relative with ovarian cancer at any age and, on the same side of the family:
    • 1 first-degree relative (including the relative with ovarian cancer) or second-degree relative diagnosed with breast cancer at younger than age 50 years or
    • 2 first-degree or second-degree relatives diagnosed with breast cancer at younger than an average age of 60 years or
    • another ovarian cancer at any age. or
  • Families affected by bilateral cancer (each breast cancer has the same count value as 1 relative):
    • 1 first-degree relative with cancer diagnosed in both breasts at younger than an average age 50 years or
    • 1 first-degree or second-degree relative diagnosed with bilateral cancer and 1 first or second degree relative diagnosed with breast cancer at younger than an average age of 60 years. or
  • Families containing male breast cancer at any age and, on the same side of the family, at least:
    • 1 first-degree or second-degree relative diagnosed with breast cancer at younger than age 50 years or
    • 2 first-degree or second-degree relatives diagnosed with breast cancer at younger than an average age of 60 years. or
  • A formal risk assessment has given risk estimates of:
    • a 10% or greater chance of a gene mutation being harboured in the family (see the eighth to 13^th recommendations the section on genetic testing) or
    • a greater than 8% risk of developing breast cancer in the next 10 years or
    • a 30% or greater lifetime risk of developing breast cancer.
• Clinicians should seek further advice from a specialist genetics service for families containing any of the following, in addition to breast cancers:
  • triple negative breast cancer under the age of 40 years
  • Jewish ancestry
  • sarcoma in a relative younger than age 45 years
  • glioma or childhood adrenal cortical carcinomas
  • complicated patterns of multiple cancers at a young age
  • very strong paternal history (4 relatives diagnosed at younger than 60 years of age on the father's side of the family).
• The management of high-risk people may take place in secondary care if they do not want genetic testing or risk-reducing surgery and do not wish to be referred to a specialist genetics service.
• Following initial consultation in secondary care, written information should be provided to reflect the outcomes of the consultation. 

Care of People in a Specialist Genetic Clinic

• Care of people referred to a specialist genetic clinic should be undertaken by a multi-disciplinary team. In addition to having access to the components found in secondary care, it should also include the following:
  • clinical genetic risk assessment
  • verification for abdominal malignancies and possible sarcomas.

Genetic Counselling for People With no Personal History of Breast Cancer

• Women with no personal history of breast cancer meeting criteria for referral to a specialist genetic clinic should be offered a referral for genetic counselling regarding their risks and options.
• Women attending genetic counselling should receive standardised information beforehand describing the process of genetic counselling, information to obtain prior to the counselling session, the range of topics to be covered and brief educational material about hereditary breast cancer and genetic testing.
• Predictive genetic testing should not be offered without adequate genetic counselling.

Genetic Testing

• All eligible people should have access to information on genetic tests aimed at mutation finding.
• Pre-test counselling (preferably 2 sessions) should be undertaken.
• Discussion of genetic testing (predictive and mutation finding) should be undertaken by a healthcare professional with appropriate training.
• Eligible people and their affected relatives should be informed about the likely informativeness of the test (the meaning of a positive and a negative test) and the likely timescale of being given the results.

Mutation Tests

• Tests aimed at mutation finding should first be carried out on an affected family member where possible.
• If possible, the development of a genetic test for a family should usually start with the testing of an affected individual (mutation searching/screening) to try to identify a mutation in the appropriate gene (such as BRCA1, BRCA2 or TP53) (see the next section).
• A search/screen for a mutation in a gene (such as BRCA1, BRCA2 or TP53) should aim for as close to 100% sensitivity as possible for detecting coding alterations and the whole gene(s) should be searched.

Carrier Probability at Which Genetic Testing Should be Offered

• Discuss the potential risk and benefits of genetic testing. Include in the discussion the probability of finding a mutation, the implications for the individual and the family, and the implications of either a variant of uncertain significance or a null result (no mutation found).
• Inform families with no clear genetic diagnosis that they can request review in the specialist genetic clinic at a future date.
• Clinical genetics laboratories should record gene variants of uncertain significance and known pathogenic mutations in a searchable electronic database.

Genetic Testing for a Person With no Personal History of Breast Cancer But With an Available Affected Relative

• Offer genetic testing in specialist genetic clinics to a relative with a personal history of breast and/or ovarian cancer if that relative has a combined BRCA1 and BRCA2 mutation carrier probability of 10% or more.

Genetic Testing for a Person With no Personal History of Breast Cancer and no Available Affected Relative to Test

• Offer genetic testing in specialist genetic clinics to a person with no personal history of breast or ovarian cancer if their combined BRCA1 and BRCA2 mutation carrier probability is 10% or more and an affected relative is unavailable for testing.

Genetic Testing for a Person with Breast or Ovarian Cancer

• Offer genetic testing in specialist genetic clinics to a person with breast or ovarian cancer if their combined BRCA1 and BRCA2 mutation carrier probability is 10% or more.

BRCA1 BRCA2 TP53 Genetic Testing for, and Mutations Within 4 Weeks of Diagnosis of Breast Cancer

• Offer people eligible for referral to a specialist genetic clinic a choice of accessing genetic testing during initial management or at any time thereafter.
• Offer fast-track genetic testing (within 4 weeks of a diagnosis of breast cancer) only as part of a clinical trial.
• Discuss the individual needs of the person with the specialist genetics team as part of the multidisciplinary approach to care.
• Offer detailed consultation with a clinical geneticist or genetics counsellor to all those with breast cancer who are offered genetic testing, regardless of the timeframe for testing.

See the full guideline for recommendations on surveillance and strategies for early detection of breast cancer.

Risk Reduction and Treatment Strategies

See the full guideline for recommendations about risk factors, menstrual and reproductive factors, hormonal contraceptives, breastfeeding, hormone replacement therapy, alcohol consumption, smoking, weight, and physical activity.

Chemoprevention for Women with no Personal History of Breast Cancer

• Healthcare professionals within secondary care or specialist genetic clinics should discuss the absolute benefits and risks of options for chemoprevention with women at high risk or moderate risk of breast cancer. Discussion, using a decision aid, should include the following to promote shared decision-making and informed preferences:
  • the reduced risk of invasive breast cancer
  • the lack of effect on mortality
  • the side effects of the different options
  • alternative approaches, such as surveillance alone and, for women at high risk, risk-reducing surgery.

Women should all be given information in an accessible format.

Recommendations About Chemoprevention for Women at High Risk of Breast Cancer

• Offer tamoxifen for 5 years to premenopausal women at high risk of breast cancer unless they have a past history or may be at increased risk of thromboembolic disease or endometrial cancer.
• Offer anastrozole for 5 years to postmenopausal women at high risk of breast cancer unless they have severe osteoporosis.

In March 2017 this was an off-label use of anastrozole. See NICE's information on prescribing medicines. Women with or at risk of osteoporosis should have their bone mineral density assessed when starting treatment and then at regular intervals. Treatment or prophylaxis for osteoporosis should be started when needed and carefully monitored.

• For postmenopausal women at high risk of breast cancer who have severe osteoporosis or do not wish to take anastrozole:
  • offer tamoxifen for 5 years if they have no history or increased risk of thromboembolic disease or endometrial cancer, or
  • consider raloxifene for 5 years for women with a uterus if they have no history or increased risk of thromboembolic disease and do not wish to take tamoxifen.

In March 2017 this was an off-label use of raloxifene. See NICE's information on prescribing medicines.

• Do not offer chemoprevention to women who were at high risk of breast cancer but have had bilateral risk-reducing mastectomy.

Recommendations About Chemoprevention for Women at Moderate Risk of Breast Cancer

• Consider tamoxifen for 5 years for premenopausal women at moderate risk of breast cancer, unless they have a past history or may be at increased risk of thromboembolic disease or endometrial cancer.
• Consider anastrozole for 5 years for postmenopausal women at moderate risk of breast cancer unless they have severe osteoporosis.

In March 2017 this was an off-label use of anastrozole. See NICE's information on prescribing medicines. Women with or at risk of osteoporosis should have their bone mineral density assessed when starting treatment and then at regular intervals. Treatment or prophylaxis for osteoporosis should be started when needed and carefully monitored.

• For postmenopausal women at moderate risk of breast cancer who have severe osteoporosis or do not wish to take anastrozole:
  • consider tamoxifen for 5 years if they have no history or increased risk of thromboembolic disease or endometrial cancer, or
  • consider raloxifene for 5 years for women with a uterus if they have no history or increased risk of thromboembolic disease and do not wish to take tamoxifen.

In March 2017 this was an off-label use of raloxifene. See NICE's information on prescribing medicines.

Recommendations for All Women Taking Drugs for Chemoprevention

• Do not continue chemoprevention beyond 5 years in women with no personal history of breast cancer.
• Inform women that they should stop tamoxifen at least:
  • 2 months before trying to conceive
  • 6 weeks before elective surgery.

Risk-reducing Mastectomy for Women With no Personal History of Breast Cancer

• Bilateral risk-reducing mastectomy is appropriate only for a small proportion of women who are from high-risk families and should be managed by a multidisciplinary team.
• Bilateral mastectomy should be raised as a risk-reducing strategy option with all women at high risk.
• Women considering bilateral risk-reducing mastectomy should have genetic counselling in a specialist cancer genetic clinic before a decision is made.
• Discussion of individual breast cancer risk and its potential reduction by surgery should take place and take into account individual risk factors, including the woman's current age (especially at extremes of age ranges).
• Family history should be verified where no mutation has been identified before bilateral risk-reducing mastectomy.
• Where no family history verification is possible, agreement by a multidisciplinary team should be sought before proceeding with bilateral risk-reducing mastectomy.
• Pre-operative counselling about psychosocial and sexual consequences of bilateral risk-reducing mastectomy should be undertaken.
• The possibility of breast cancer being diagnosed histologically following a risk-reducing mastectomy should be discussed pre-operatively.
• All women considering bilateral risk-reducing mastectomy should be able to discuss their breast reconstruction options (immediate and delayed) with a member of a surgical team with specialist oncoplastic or breast reconstructive skills.
• A surgical team with specialist oncoplastic/breast reconstructive skills should carry out risk-reducing mastectomy and/or reconstruction.
• Women considering bilateral risk-reducing mastectomy should be offered access to support groups and/or women who have undergone the procedure.

Risk-reducing Oophorectomy for Women With no Personal History of Breast Cancer

• Risk-reducing bilateral oophorectomy is appropriate only for a small proportion of women who are from high-risk families and should be managed by a multidisciplinary team.
• Information about bilateral oophorectomy as a potential risk-reducing strategy should be made available to women who are classified as high risk.
• Family history should be verified where no mutation has been identified before bilateral risk-reducing oophorectomy.
• Where no family history verification is possible, agreement by a multidisciplinary team should be sought before proceeding with bilateral risk-reducing oophorectomy.
• Any discussion of bilateral oophorectomy as a risk-reducing strategy should take fully into account factors such as anxiety levels on the part of the woman concerned.
• Healthcare professionals should be aware that women being offered risk-reducing bilateral oophorectomy may not have been aware of their risks of ovarian cancer as well as breast cancer and should be able to discuss this.
• The effects of early menopause should be discussed with any woman considering risk-reducing bilateral oophorectomy.
• Options for management of early menopause should be discussed with any woman considering risk-reducing bilateral oophorectomy, including the advantages, disadvantages and risk impact of HRT.
• Women considering risk-reducing bilateral oophorectomy should have access to support groups and/or women who have undergone the procedure.
• Women considering risk-reducing bilateral oophorectomy should be informed of possible psychosocial and sexual consequences of the procedure and have the opportunity to discuss these issues.
• Women not at high risk who raise the possibility of risk-reducing bilateral oophorectomy should be offered appropriate information, and if seriously considering this option should be offered referral to the team that deals with women at high risk.
• Women undergoing bilateral risk-reducing oophorectomy should have their fallopian tubes removed as well.

HRT for Women With no Personal History of Breast Cancer who Have a Bilateral Salpingo-oophorectomy Before the Natural Menopause

• When women with no personal history of breast cancer have either a BRCA1 or BRCA2 mutation or a family history of breast cancer and they have had a bilateral salpingo-oophorectomy before their natural menopause, offer them:
  • combined HRT if they have a uterus
  • oestrogen-only HRT if they don't have a uterus up until the time they would have expected natural menopause (average age for natural menopause is 51 to 52 years).
• Manage menopausal symptoms occurring when HRT is stopped in the same way as symptoms of natural menopause.

Risk-reducing Breast or Ovarian Surgery for People With a Personal History of Breast Cancer

Counselling

• Refer women with a personal history of breast cancer who wish to consider risk-reducing surgery for appropriate genetic and psychological counselling before surgery.

Risk-reducing Mastectomy

• Discuss the risks and benefits of risk-reducing mastectomy with women with a known or suspected BRCA1, BRCA2 or TP53 mutation.
• For a woman considering risk-reducing mastectomy, include in the discussion of risks and benefits:
  • the likely prognosis of their breast cancer, including their risk of developing a distal recurrence of their previous breast cancer
  • a clear quantification of the risk of developing breast cancer in the other breast
  • the potential negative impact of mastectomy on body image and sexuality
  • the very different appearance and feel of the breasts after reconstructive surgery
  • the potential benefits of reducing the risk in the other breast and relieving the anxiety about developing breast cancer.
• Give all women considering a risk-reducing mastectomy the opportunity to discuss their options for breast reconstruction (immediate and delayed) with a member of a surgical team with specialist skills in oncoplastic surgery or breast reconstruction.
• Ensure that risk-reducing mastectomy and breast reconstruction are carried out by a surgical team with specialist skills in oncoplastic surgery and breast reconstruction.
• Offer women who have BRCA1, BRCA2 or TP53 mutations but who decide against risk-reducing mastectomy, surveillance according to their level of risk.

Risk-reducing Bilateral Salpingo-oophorectomy

• Discuss the risks and benefits of risk-reducing bilateral salpingo-oophorectomy with women with a known or suspected BRCA1, BRCA2 or TP53 mutation. Include in the discussion the positive effects of reducing the risk of breast and ovarian cancer and the negative effects of a surgically induced menopause.
• Defer risk-reducing bilateral salpingo-oophorectomy until women have completed their family.

Contraindications to Risk-reducing Surgery for People With a Personal History of Breast Cancer

• Do not offer risk-reducing surgery to people with comorbidities that would considerably increase the risks of surgery.
• Do not offer risk-reducing surgery to people who have a limited life expectancy from their cancer or other conditions.

TP53 Treatment Options for People With a Personal History of Breast Cancer Who are Mutation Carriers

• When a person has invasive breast cancer or ductal carcinoma in situ and is known to have a TP53 mutation or a 30% probability of a TP53 mutation:
  • inform them of all the possible treatment options
  • make sure they know about the uncertainties associated with these treatment options
  • inform them of the risks associated with each treatment (for example, the risk of recurrence, the risk of new primary breast cancer and the risks of malignancy associated with radiotherapy and chemotherapy).
• Offer people with invasive breast cancer or ductal carcinoma in situ and a 30% probability of a TP53 mutation, genetic testing to help determine their treatment options.