Practice Guidelines

Familial breast cancer: summary of updated NICE guidance

BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f3829 (Published 25 June 2013) Cite this as: BMJ 2013;346:f3829
  1. D Gareth Evans, professor of genetic medicine1,
  2. John Graham, director and consultant in clinical oncology2,
  3. Susan O’Connell, researcher2,
  4. Stephanie Arnold, information specialist2,
  5. Deborah Fitzsimmons, health economist3
  1. 1Department of Genetic Medicine, St Mary’s Hospital, Manchester M13 9WL, UK
  2. 2National Collaborating Centre for Cancer, Cardiff CF10 3AF, UK
  3. 3Swansea Centre for Health Economics, Swansea University, Swansea SA2 8PP, UK
  1. Correspondence to: J Graham john.graham{at}nhs.net

Familial breast cancer occurs in people with one or more family members affected by breast, ovarian, or a related cancer such as primary peritoneal cancer. About 5% of all breast cancers can be attributed to inherited mutations in specific high risk genes such as BRCA1, BRCA2, and TP53.

This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on the classification and care of people at risk of familial breast cancer.1 The guideline updates previous NICE guidance on familial breast cancer, published in 2004 and 2006.2 3 It also provides new guidance on men and women with a newly or previously diagnosed breast cancer who have a family history of breast and ovarian cancer, as they were excluded from previous guidance.4

Recommendations

NICE recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets.

Information and support for patients

  • Offer patients individually tailored information, including information about sources of support (including local and national organisations). [Based on the experience and opinion of the Guideline Development Group (GDG)]

Initial assessment in primary care for people without a personal history of breast cancer

  • When a person with no personal history of breast cancer presents with breast symptoms or has concerns about relatives with breast cancer, take a first and second degree family history to assess risk, as this allows appropriate classification and care.

  • Attempt to gather information that is as accurate as possible on age of diagnosis of any cancer in relatives, site of tumours, multiple cancers (including bilateral disease), or Jewish ancestry.

  • Offer referral to secondary care for breast cancer risk estimation if the person meets any of the following criteria:

    • -One first degree female relative with breast cancer at <40 years of age

    • -One first degree male relative with breast cancer at any age

    • -One first degree relative with bilateral breast cancer where the first primary was diagnosed at <50 years of age

    • -Two first degree relatives, or one first degree plus one second degree relative, with breast cancer at any age

    • -One first degree or second degree relative with breast cancer at any age plus one first degree or second degree relative with ovarian cancer at any age (one of these should be a first degree relative)

    • -Three first degree or second degree relatives on the same side of the family with breast cancer at any age

    • -If more than one relative is involved, they should be on the same side of the family.

  • Women who do not meet these criteria can be reassured that they are at near population risk of getting breast cancer and do not require referral for specific breast cancer risk estimation.

[Based on the experience and opinion of the GDG]

Identification of gene carriers for people with or without a personal history of breast cancer

  • When available in secondary care, use a carrier probability calculation method with demonstrated acceptable performance (in 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.5 6 (New recommendation.) [Based on moderate quality evidence from diagnostic studies]

  • Offer genetic testing in specialist genetic clinics to anyone who has a combined BRCA1/BRCA2 mutation carrier probability of 10% or more. (New recommendation.) [Based on moderate quality evidence of cost effectiveness]

Ideally offer genetic testing to a family member with a personal history of breast or ovarian cancer. However, unaffected individuals can be offered testing if an affected relative is unavailable. The treatment of people with newly diagnosed breast cancer might be different if they have familial breast cancer, but there was no clinical trial evidence to support rapid testing within four weeks of a diagnosis of breast cancer.

  • Offer people eligible for referral to a specialist genetics clinic a choice of accessing genetic testing during initial management of their cancer or at any time thereafter. (New recommendation.) [Based on very low quality evidence from observational studies]

  • Offer fast track genetic testing (within four weeks of a diagnosis of breast cancer) only as part of a clinical trial. (New recommendation.) [Based on the experience and opinion of the GDG]

  • Discuss the potential risks 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 finding either a variant of uncertain significance or no mutation. (New recommendation.) [Based on the experience and opinion of the GDG]

  • As future knowledge will undoubtedly improve the identification of hereditary breast cancer, inform families with no clear genetic diagnosis that they can request review in the specialist genetic clinic at a future date. (New recommendation.) [Based on the experience and opinion of the GDG]

Breast cancer surveillance

Breast cancer risk categories. Risk estimation in secondary and tertiary care can be enhanced by use of existing risk assessment tools such as BOADICEA5 and Tyrer-Cuzick7

View this table:

Women with a family history of breast cancer, with or without a personal history of breast cancer, who have a moderate to high risk of breast cancer on specialist risk estimation (see table) and who choose not to have risk reducing mastectomy may benefit from radiological surveillance of their breasts.

  • Ensure digital mammography and breast magnetic resonance imaging (MRI) are performed to national breast screening programme standards. (New recommendation.) [Based on moderate quality evidence of clinical and cost effectiveness]

MRI screening was shown to be more cost effective than mammography for high risk women with a known BRCA or TP53 mutation or >30% probability of being a mutation carrier.

  • Offer annual MRI to women aged 30-49, with or without a personal history of breast cancer, if they have a BRCA1 or BRCA2 mutation or have a >30% risk of being a BRCA carrier. (New and updated recommendation.) [Based on moderate quality evidence of clinical and cost effectiveness]

  • Offer annual mammographic surveillance to women:

    • -Aged 40-49 years at moderate risk of breast cancer

    • -Aged 40-59 years at high risk of breast cancer but with a ≤30% probability of a BRCA or TP53 mutation

    • -Aged 40-59 years with a >30% probability of being a BRCA carrier

    • -Aged 40-69 years with a known BRCA1 or BRCA2 mutation.

    • (Updated recommendation.) [Based on moderate quality evidence of clinical and cost effectiveness]

  • Do not offer mammography to women aged <30 years or to women of any age with a known TP53 mutation. (New recommendation.) [Based on the experience and opinion of the GDG]

  • Do not routinely offer ultrasound surveillance to women at moderate or high risk of breast cancer but consider it when MRI surveillance would normally be offered but is not suitable (for example, because of claustrophobia) or when results of mammography or MRI are difficult to interpret. (New recommendation.) [Based on the experience and opinion of the GDG]

Risk reduction strategies for women with no personal history of breast cancer

Hormone replacement therapy and the oral contraceptives can increase the risk of developing breast cancer.

  • Inform women aged >35 years with a family history of breast cancer of the increased risk of breast cancer associated with taking oral contraceptives, given that their absolute risk increases with age. [Based on very low quality evidence from observational studies]

  • For women with BRCA mutations, discuss the conflicting effects of a potential increased risk of breast cancer at ages <40 years and the lifetime protection against ovarian cancer risk from taking oral contraceptives. [Based on very low quality evidence from observational studies]

  • For women with a family history of breast cancer who are considering taking or already taking hormone replacement therapy, inform them of the increase in breast cancer risk with type and duration of hormone replacement therapy. [Based on very low quality evidence from observational studies]

Recent trial results have shown a significant reduction in the risk of breast cancer for the drugs tamoxifen and raloxifene. Both drugs can cause thromboembolic disease, and tamoxifen can cause endometrial cancer. However both drugs are cost effective.

After specialist risk assessment, for women who have no history of breast cancer and are not at increased risk of thromboembolic disease or endometrial cancer:

  • Offer tamoxifen for five years if they are premenopausal and at high risk of breast cancer. (New recommendation.) [Based on moderate to high quality evidence from randomised controlled trials (RCTs) and cost analysis]

  • Offer tamoxifen for five years if they are postmenopausal, at high risk of breast cancer, and do not have a uterus. (New recommendation.) [Based on moderate to high quality evidence from RCTs and cost analysis]

  • Offer either tamoxifen or raloxifene for five years if they are postmenopausal, at high risk of breast cancer, and have a uterus. (New recommendation.) [Based on moderate to high quality evidence from RCTs and cost analysis]

  • Consider prescribing tamoxifen for five years if they are premenopausal and at moderate risk of developing breast cancer within the next 10 years. (New recommendation.) [Based on the experience and opinion of the GDG and cost analysis]

  • Consider prescribing tamoxifen for five years if they are postmenopausal, at moderate risk of developing breast cancer within the next 10 years, and do not have a uterus. (New recommendation.) [Based on the experience and opinion of the GDG and cost analysis]

  • Consider prescribing either tamoxifen or raloxifene for five years if they are postmenopausal, at moderate risk of developing breast cancer within the next 10 years, and have a uterus. (New recommendation.) [Based on the experience and opinion of the GDG and cost analysis]

Risk reduction strategies for all women with a family history of breast or ovarian cancer

Women at increased risk of developing breast or ovarian cancer due to their family history may consider surgery as an option to reduce this risk. For women with newly diagnosed breast cancer this may result in different surgical options than for women with no family history.

  • Discuss the risks and benefits of risk reducing mastectomy with women with a known or suspected BRCA1, BRCA2, or TP53 mutation. (New and updated recommendation.)

  • Ensure that risk reducing mastectomy and breast reconstruction are carried out by a surgical team with specialist skills in oncoplastic surgery and breast reconstruction. (New recommendation.)

  • 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. (New and updated recommendation.)

  • Discuss the benefit and risks of hormone replacement therapy after oophorectomy for women aged ≤50 years without breast cancer. (New recommendation.)

[All points based on very low quality evidence from observational studies]

Overcoming barriers

The lower thresholds for genetic testing recommended in the guideline will increase the number of referrals to specialist genetic clinics, but, in the view of the Guideline Development Group, the current infrastructure should be able to deal with this. In England the NHS Breast Screening Programme has recently updated its recommendations for surveillance of women with a family history of breast cancer,8 and these are in alignment with most of the guideline recommendations.

Further information on the guidance

Methods

This guidance was developed by the National Collaborating Centre for Cancer using methods from NICE’s standard processes (www.nice.org.uk/guidelinesmanual). The guidance review process involved literature searches to identify relevant evidence, with critical appraisal of the quality of the identified evidence. A multidisciplinary team of service users, carers, and healthcare professionals (including clinical geneticists, an epidemiologist, a radiologist, a general practitioner, a breast cancer surgeon, an oncologist, and patient and carer representatives) (the Guideline Development Group) was established to review the evidence and develop the subsequent recommendations. The guidance then went through an external consultation with stakeholders. The GDG considered the stakeholders’ comments, reanalysed the data where necessary, and modified the guidance as appropriate.

NICE has produced three different versions of the guidance: a full version; a summary version known as the “NICE guidance”; and a version for people using NHS services, their families and carers, and the public. All these versions, as well as a pathway and tools to aid implementation of this guideline, are available from the NICE website. Further updates of the guidance will be produced as part of NICE’s guideline development programme.

Future research

The GDG has made the following recommendations for research:

  • To develop and validate models for calculating gene carrier probability that incorporate additional data such as the molecular pathology of tumours and the prevalence of mutations in different ethnic groups

  • To determine the benefits and harms of creating rapid access to genetic testing for people with newly diagnosed breast cancer; this should evaluate the optimum model for service delivery and organisation, the clinical and cost effectiveness of such a change, uptake outcomes, and patients’ experience

  • To establish the risk and benefits of MRI surveillance compared with mammography in women >50 years old with a personal history of breast cancer; studies should include sub-analysis for breast density

  • A randomised controlled trial to compare the clinical and cost effectiveness of aromatase inhibitors and tamoxifen for reducing the incidence of breast cancer in women with a family history of breast or ovarian cancer

  • To compare psychosocial and clinical outcomes in women who chose to have risk reducing surgery and women who chose not to.

Notes

Cite this as: BMJ 2013;346:f3829

Footnotes

  • This is one of a series of BMJ summaries of new guidelines based on the best available evidence; they highlight important recommendations for clinical practice, especially where uncertainty or controversy exists.

  • The members of the Guideline Development Group were Maggie Alexander (chair), Gareth Evans, Amanda Taylor, Nadeem Qureshi, Andrew Cuthbert, Anneke Lucassen, Diana Eccles, Fiona Gilbert, Anne Armstrong, Susan Heard, Paul Pharaoh, Nina Hallowell, Ulrike Harrower, Kathie Binysh, Ursula Van Mann, Wendy Watson, and Caitlin Palframan.

  • Contributors: All authors contributed to the conception and drafting of this article and revising it critically. They have all approved this version. JG is the guarantor. Lianne Gwillim of the National Collaborating Centre for Cancer, was project manager for the guideline development process and was responsible for collating and editing the guideline for publication

  • Competing interests: We have read and understood the BMJ Group policy on declaration of interests and declare the following interests: JG, SO’C, SA, and DF received funding from NICE to support guideline development at the National Collaborating Centre for Cancer.

  • Provenance and peer review: Commissioned; not externally peer reviewed.

References