Familial Breast Cancer

 

Health guidance

No need of more invetigations 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)

Need for further investigations

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.

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 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.

Genetic testing

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:

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: 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.

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.

Risk reduction and treatment strategies

Hormonal contraceptives:

Advice to women up to age 35 years with a family history of breast cancer should be in keeping with general health advice on the use of the oral contraceptive pill.

A family history of breast cancer is not a contra-indication to any form of hormonal contraception.

Women aged over 35 years with a family history of breast cancer should be informed of an increased risk of breast cancer associated with taking the oral contraceptive pill, given that their absolute risk increases with age.

For women with BRCA1 mutations, there are conflicting effects of a potential increased risk of breast cancer under the age of 40 years and the lifetime protection against ovarian cancer risk from taking the oral contraceptive pill.

Women should not be prescribed the oral contraceptive pill purely for prevention of cancer, although in some situations reduction in ovarian cancer risk may outweigh any increase in risk of breast cancer.

If a woman has a BRCA1 mutation and is considering a risk-reducing oophorectomy before the age of 40 years, the oral contraceptive pill should not be prescribed purely for the reduction in ovarian cancer risk.

Hormone replacement therapy (HRT):

Women with a family history of breast cancer who are considering taking, or are already taking, HRT should be informed of the increase in breast cancer risk.

HRT usage in a woman at familial risk should be restricted to as short a duration and as low a dose as possible. Oestrogen-only HRT should be prescribed where possible.

A woman having an early (natural or artificial) menopause should be informed of the risks and benefits of HRT, but generally HRT usage should be confined to women younger than age 50 years if at moderate or high risk.

Alternatives to HRT should be considered for specific symptoms such as osteoporosis or menopausal symptoms.

Alcohol consumption – women with a family history should be informed that alcohol may increase their risk of breast cancer slightly.

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 and raloxifene reduce the risk of breast cancer in women at increased risk of disease.

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.

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

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^] 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

Terms

Genetic breast cancer

Familial breast cancer

Detection of familial breast cancer

People with high risk of breast cancer

Breast cancer

Precanceros breast lumps

Breast lump

Breast cancer screening

Bowel (Colonic) Polyps (Familial)

Understanding the gut

​Familial Breast Cancer

Health guidance

No need of more invetigations 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)

Need for further investigations

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.

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 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.

Genetic testing

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:

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: 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.

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.

Risk reduction and treatment strategies

Hormonal contraceptives:

Advice to women up to age 35 years with a family history of breast cancer should be in keeping with general health advice on the use of the oral contraceptive pill.

A family history of breast cancer is not a contra-indication to any form of hormonal contraception.

Women aged over 35 years with a family history of breast cancer should be informed of an increased risk of breast cancer associated with taking the oral contraceptive pill, given that their absolute risk increases with age.

For women with BRCA1 mutations, there are conflicting effects of a potential increased risk of breast cancer under the age of 40 years and the lifetime protection against ovarian cancer risk from taking the oral contraceptive pill.

Women should not be prescribed the oral contraceptive pill purely for prevention of cancer, although in some situations reduction in ovarian cancer risk may outweigh any increase in risk of breast cancer.

If a woman has a BRCA1 mutation and is considering a risk-reducing oophorectomy before the age of 40 years, the oral contraceptive pill should not be prescribed purely for the reduction in ovarian cancer risk.

Hormone replacement therapy (HRT):

Women with a family history of breast cancer who are considering taking, or are already taking, HRT should be informed of the increase in breast cancer risk.

HRT usage in a woman at familial risk should be restricted to as short a duration and as low a dose as possible. Oestrogen-only HRT should be prescribed where possible.

A woman having an early (natural or artificial) menopause should be informed of the risks and benefits of HRT, but generally HRT usage should be confined to women younger than age 50 years if at moderate or high risk.

Alternatives to HRT should be considered for specific symptoms such as osteoporosis or menopausal symptoms.

Alcohol consumption – women with a family history should be informed that alcohol may increase their risk of breast cancer slightly.

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 and raloxifene reduce the risk of breast cancer in women at increased risk of disease.

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.

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

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^] 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