Familial Breast Cancer

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PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

See also: Breast Cancer - Hereditary Factors written for patients

Several genetic risk factors have been identified, the most common being BRCA1 and BRCA2:[1] 

  • BRCA1 mutation on chromosome 17: the lifetime risk of breast cancer for women with this mutation is 65-85% and the lifetime risk of ovarian cancer is 40-50%; men with this mutation may be at increased risk of breast cancer.
  • BRCA2 mutation on chromosome 13: the lifetime risk of breast cancer for women with this mutation is 40-85% and the lifetime risk of ovarian cancer is 10-25%; for men with this mutation, the lifetime risk of breast cancer is 6%.
  • TP53 mutation on chromosome 17: most women with this mutation develop breast cancer by 50 years of age.
  • PTEN gene: Cowden's syndrome (predisposes to breast cancer, thyroid cancer, uterine cancer and hamartomatous lesions of the skin).
  • ATM, CHEK2, BRIP1, and PALB2 genes: moderate risk of breast cancer.

A Cochrane review found favourable outcomes for patients after risk assessment for familial breast cancer.[2] Local protocols should exist (or be developed) for the care of women at risk of familial breast cancer. There should be clear referral mechanisms between primary, secondary and tertiary care.

When a family history of breast cancer is identified during a consultation, a careful family tree of affected individuals should be constructed and patients reassured or referred appropriately.

Women can be cared for in primary care without secondary care referral (offer appropriate information and reassurance) if the family history shows only one first-degree or second-degree relative diagnosed with breast cancer at an age older than 40 years, provided that none of the following is present in the family history:

  • Bilateral breast cancer.
  • Male breast cancer.
  • Ovarian cancer.
  • 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.
  • Paternal history of breast cancer (two or more relatives on the father's side of the family).

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People without a personal history of breast cancer who meet the following criteria should be offered referral to secondary care:

  • One first-degree female relative diagnosed with breast cancer at younger than age 40 years.
  • One first-degree male relative diagnosed with breast cancer at any age.
  • One first-degree relative with bilateral breast cancer where the first primary was diagnosed at younger than age 50 years.
  • Two first-degree relatives, or one first-degree and one second-degree relative, diagnosed with breast cancer at any age.
  • One first-degree or second-degree relative diagnosed with breast cancer at any age and one first-degree or second-degree relative diagnosed with ovarian cancer at any age (one of these should be a first-degree relative).
  • Three first-degree or second-degree relatives diagnosed with breast cancer at any age.

People who meet the following referral criteria should be offered a referral to a specialist genetic clinic:

  • At least the following female breast cancers in the family:
    • Two first-degree or second-degree relatives diagnosed with breast cancer at younger than an average age of 50 years (at least one must be a first-degree relative); or
    • Three first-degree or second-degree relatives diagnosed with breast cancer at younger than an average age of 60 years (at least one must be a first-degree relative); or
    • Four relatives diagnosed with breast cancer at any age (at least one must be a first-degree relative); or
  • Families containing one relative with ovarian cancer at any age and, on the same side of the family:
    • One first-degree relative (including the relative with ovarian cancer); or
    • One second-degree relative diagnosed with breast cancer at younger than age 50 years; or
    • Two 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 one relative):
    • One first-degree relative with cancer diagnosed in both breasts at younger than an average age 50 years; or
    • One first-degree or second-degree relative diagnosed with bilateral cancer and one first-degree 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:
    • One first-degree or second-degree relative diagnosed with breast cancer at younger than age 50 years; or
    • Two 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; or
    • A greater than 8% risk of developing breast cancer in the following 10 years; or
    • A 30% or greater lifetime risk of developing breast cancer.
  • A first- and second-degree family history should be taken in primary care when a woman presents with breast symptoms, or has concerns about relatives with breast cancer. This will assess risk and allow proper classification and care, as above.[1] 
  • The woman should be given information concerning breast awareness and self-examination.
  • The woman should be advised to return if her family history changes, or breast symptoms develop.
  • Women should have access to psychological support and assessment where necessary. Information on local or national support groups should be available.
  • Appropriate lifestyle advice should be offered regarding risk factors - eg, contraception, smoking and alcohol.

Some centres use predictive models for risk assessment and only test when the risk of finding a gene mutation is 10-20%. Otherwise, generally accepted criteria include:[4] 

  • Three or more breast and/or ovarian cancer cases with at least one case in a woman aged younger than 50 years.
  • Two breast cancer cases where younger than 40 years.
  • Male breast cancer and an ovarian cancer or early-onset female breast cancer case.
  • Ashkenazi Jewish background with breast cancer in a woman aged younger than 60 years.
  • Young-onset bilateral breast cancer.
  • Breast and ovarian cancer in the same patient.

Testing should only be carried out after the patient has received appropriate genetic counselling and they have given informed consent.

Screening and surveillance

Family history and carrier probability:

  • A carrier probability calculation method as well as family history should be used in secondary care when available to determine who should be offered referral to a specialist genetic clinic.
  • Examples of acceptable methods include BOADICEA and the Manchester scoring system:[5] 
    • BOADICEA is a computer program that is used to estimate BRCA1/BRCA2 mutation carrier probabilities and breast/ovarian cancer risks on the basis of family history.[6] 

Carrier probability at which genetic testing should be offered

  • 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.
  • 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.

Surveillance for women with no personal history of breast cancer

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% or lower probability of being a BRCA or TP53 carrier.
  • Aged 40-59 years who have not had genetic testing but have a greater than 30% probability of being a BRCA carrier.
  • Aged 40-69 years with a known BRCA1 or BRCA2 mutation.

Offer annual MRI surveillance to women:

  • Aged 30-49 years who have not had genetic testing but have a greater than 30% probability of being a BRCA carrier.
  • Aged 30-49 years with a known BRCA1 or BRCA2 mutation.
  • Aged 20-49 years who have not had genetic testing but have a greater than 30% probability of being a TP53 carrier.
  • Aged 20-49 years with a known TP53 mutation.

Surveillance for women with a personal and family history of breast cancer

  • Offer annual mammographic surveillance to all women aged 50-69 years with a personal history of breast cancer who remain at high risk of breast cancer (including those who have a BRCA1 or BRCA2 mutation), and do not have a TP53 mutation.
  • Offer annual MRI surveillance to all women aged 30-49 years with a personal history of breast cancer who remain at high risk of breast cancer, including those who have a BRCA1 or BRCA2 mutation.
  • Hormonal contraceptives:[1]
    • For women with a family history of breast cancer who are not known to be carriers of a gene mutation, any form of hormonal contraception or intrauterine device may be used.
    • For women who are known carriers of a gene mutation associated with breast cancer (such as BRCA1):
      • Discuss the use of combined hormone contraception with a specialist genetics service as views are conflicting on whether or not the protective effects of combined hormone contraception against ovarian cancer outweigh the increased risk of breast cancer.
      • The progestogen-only pill, depot medroxyprogesterone acetate, the etonogestrel-only implant or the levonorgestrel-releasing intrauterine system (Mirena®) may generally be used..
  • Hormone replacement therapy (HRT):[1] 
    • If the woman is at low risk of breast cancer (ie they do not fulfil the referral criteria to secondary care), HRT may be prescribed.
    • If they are at increased risk of breast cancer (ie they fulfil the referral criteria to secondary care):
      • Ensure they have been referred to secondary care for assessment of their breast cancer risk.
      • Inform them of the increase in breast cancer risk with type and duration of HRT and refer them to secondary care for advice as to whether or not it is appropriate to prescribe HRT.[7]
  • Alcohol consumption - women with a family history should be informed that alcohol may increase their risk of breast cancer slightly.[8]
  • Women should be advised not to smoke, in line with current health advice.
  • Women should be advised on the probable increased postmenopausal risk of breast cancer from being overweight.
  • Women should be advised about the potential benefits of physical exercise on breast cancer risk.

Chemoprevention for women with no personal history of breast cancer

Tamoxifen reduces the risk of breast cancer in women at increased risk of disease.[9] 

The National Institute for Health and Care Excellence (NICE) recommends:[3] 

  • Offer tamoxifen for five 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 tamoxifen for five years to postmenopausal women without a uterus and at high risk of breast cancer unless they have a past history or may be at increased risk of thromboembolic disease or they have a past history of endometrial
    cancer.
  • Offer either tamoxifen or raloxifene for five years to postmenopausal women with a uterus and at high risk of breast cancer unless they have a past history or may be at increased risk of thromboembolic disease or endometrial cancer.
  • Consider prescribing tamoxifen for five years to premenopausal women or to postmenopausal women without a uterus who are at moderate risk of developing breast cancer, unless they have a past history or may be at increased risk of thromboembolic disease or endometrial cancer.
  • Do not offer tamoxifen or raloxifene to women who were at high risk of breast cancer but have had a bilateral mastectomy.
  • Consider prescribing either tamoxifen or raloxifene for five years to postmenopausal women with a uterus and at moderate risk of developing breast cancer, unless they have a past history or may be at increased risk of thromboembolic disease or endometrial cancer.
  • Do not continue treatment with tamoxifen or raloxifene beyond five years for chemoprevention in women with no personal history of breast cancer.

Risk-reducing mastectomy for women with no personal history of breast cancer

Bilateral prophylactic mastectomy and contralateral prophylactic mastectomy are effective at reducing both the incidence of and death from breast cancer and should be discussed with those women at very high risk of breast cancer.[10] 

All women considering bilateral risk-reducing mastectomy should be able to discuss their breast reconstruction options with a member of a surgical team with specialist oncoplastic or breast reconstructive skills.

  • Studies have shown a risk reduction of at least 90% with prophylactic bilateral mastectomy.[4] It is the most effective strategy for risk reduction in carriers of the BRCA mutation.
  • There is also evidence to support prophylactic bilateral salpingo-oophorectomy.[11]

Further reading & references

  1. Breast cancer - managing FH; NICE CKS, December 2013 (UK access only)
  2. Hilgart JS, Coles B, Iredale R; Cancer genetic risk assessment for individuals at risk of familial breast cancer. Cochrane Database Syst Rev. 2012 Feb 15;2:CD003721.
  3. Familial breast cancer: Classification and care of people at risk of familial breast cancer and management of breast cancer and related risks in people with a family history of breast cancer; NICE Clinical Guideline (June 2013)
  4. BRCA in breast cancer: ESMO Clinical Practice Guidelines; European Society for Medical Oncology (2011)
  5. Gadzicki D, Evans DG, Harris H, et al; Genetic testing for familial/hereditary breast cancer-comparison of guidelines and recommendations from the UK, France, the Netherlands and Germany. J Community Genet. 2011 Jun;2(2):53-69. doi: 10.1007/s12687-011-0042-4. Epub 2011 Mar 2.
  6. BOADICEA; Centre for Cancer Genetic Epidemiology
  7. Marjoribanks J, Farquhar C, Roberts H, et al; Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2012 Jul 11;7:CD004143. doi: 10.1002/14651858.CD004143.pub4.
  8. Kent A; Alcohol and breast cancer. Rev Obstet Gynecol. 2012;5(1):57.
  9. Cuzick J, Sestak I, Bonanni B, et al; Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data. Lancet. 2013 May 25;381(9880):1827-34. doi: 10.1016/S0140-6736(13)60140-3. Epub 2013 Apr 30.
  10. Lostumbo L, Carbine NE, Wallace J; Prophylactic mastectomy for the prevention of breast cancer. Cochrane Database Syst Rev. 2010 Nov 10;(11):CD002748. doi: 10.1002/14651858.CD002748.pub3.
  11. Nathanson KL, Domchek SM; Therapeutic approaches for women predisposed to breast cancer. Annu Rev Med. 2011;62:295-306.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Hayley Willacy
Current Version:
Peer Reviewer:
Dr John Cox
Document ID:
4074 (v25)
Last Checked:
03/07/2016
Next Review:
02/07/2021

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