Drugs to be offered to women at high risk of breast cancer

The National Institute of Health and Care Excellence (NICE) has today released updated guidelines on the care of women who are at increased risk of breast cancer due to their family history. One of the main changes to the original guidance from 2004 is that NICE now recommends drug treatment with tamoxifen or raloxifene to reduce risk of breast cancer in a specific group of women who are at high risk of breast cancer and have not had the disease.

They say that these treatments could help prevent breast cancer in about 488,000 women aged 35 years and older.

The updated guideline has also made changes to the recommended level of risk at which relatives of a woman with familial breast cancer can be offered genetic testing, and to the screening offered to specific groups of women.

What is familial breast cancer?

Breast cancer is referred to as “familial” when there are an unusually high number of cases of breast, ovarian or related cancers in a family – more than would be expected by chance alone.

This may be an indication that faulty genes have caused or contributed to the development of the cancer. Three of the genes that are known to be involved in causing familial breast cancer are BRCA1, BRCA2 and TP53.

Read more about the genetics of breast cancer

How is a woman’s risk assessed?

In cases where breast cancer runs in a family, doctors can estimate a woman’s risk of breast cancer based on:

• her age
• the age at which her relatives developed breast cancer
• the number of her relatives that have developed breast, ovarian or a related cancer
• the exact nature of her family history (e.g. who has been affected)

The NICE guideline lays out how doctors should carry out this assessment and estimate a woman’s risk. It recommends that women who have not had breast cancer who meet the following criteria should be offered referral to secondary care by their GP:

• one first-degree female relative (mother, daughter or sister) diagnosed with breast cancer at younger than the age of 40, or
• one first-degree male relative (father, son, or brother) diagnosed with breast cancer at any age, or
• one first-degree relative with bilateral breast cancer where the first primary was diagnosed at younger than 50, or
• two first-degree relatives, or one first-degree and one second-degree relative (grandparent, grandchild, aunt, uncle, niece, nephew, half-sister or half-brother), diagnosed with breast cancer at any age, or
• 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), or
• three first-degree or second-degree relatives diagnosed with breast cancer at any age

If the woman has relatives with breast cancer but does not meet these criteria, if her family history includes any of the following the GP should seek advice from secondary care:

• breast cancer in both breasts
• ovarian cancer
• male breast cancer
• Jewish ancestry
• sarcoma before the age of 45
• glioma or childhood adrenal cortical carcinomas
• multiple cancers at a young age
• two or more relatives on the father’s side with breast cancer

Women with mutations in BRCA1, BRCA2 or TP53 should be referred directly to a specialist genetics clinic (see below for more information on genetic testing).

The NICE guideline also gives detailed family history criteria that suggest that a woman should be offered referral to a specialist genetics clinic for further assessment and potentially genetic counselling and genetic testing. Women should be offered referral if their risk assessment finds that they have:

• a 10% or greater chance of a gene mutation being present in their family (a new recommendation for this updated guidance)
• 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

How is a woman’s risk classified?

The NICE guideline gives recommendations to doctors on exactly which computer programs and methods can be used to calculate a woman’s breast cancer risk.

Women whose lifetime risk from age 20 is estimated to be more than 17% but less than 30% are considered to be at moderate risk, and those at 30% or greater risk are considered to be at high risk. Women whose risk between the ages of 40 and 50 is estimated to be 3-8% are considered to be moderate risk and those at more than 8% risk are considered to be high risk.

What changes are there in NICE’s recommendations on surveillance?

NICE’s guideline gives detailed recommendations on exactly what kind of surveillance should or should not be offered to women with familial breast cancer for early detection of breast cancer. This is based on their specific levels of risk, age and genetic make-up.

The changes in the updated guidance include:

• offering annual mammographic surveillance to women aged 40-69 with a known BRCA1 or BRCA2 mutation
• offering annual mammographic surveillance to all women aged 50-69 who have or have had breast cancer who remain at high risk of the disease and do not have TP53 mutation
• offering annual MRI surveillance to all women aged 30-49 who have or have had breast cancer who remain at high risk of the disease, including those who have a BRCA1 or BRCA2 mutation

What changes are there in NICE’s recommendations on genetic testing?

As in their previous guidance, NICE recommends that genetic testing for a family should first be carried out on an affected family member if possible, to try and identify whether they carry a mutation in genes such as BRCA1, BRCA2 or TP53.

However, if an affected relative is not available, NICE’s new recommendation is that genetic testing can be offered to relatives of people affected by familial breast cancer if their combined risk of carrying a mutation in BRCA1 or BRCA2 is 10% or more. Previously this was recommended only if their combined risk was 20% or more. Genetic testing can also be offered to individuals with breast or ovarian cancer if their combined BRCA1 and BRCA2 mutation carrier probability is 10% or more.

What changes are there in NICE’s recommendations on preventative drug treatment?

The main change reported on in the news is that NICE now recommends offering the drugs tamoxifen or raloxifene to specific groups of women at risk of familial breast cancer to reduce their chances of getting the disease.

NICE recommends that:

• Healthcare professionals in specialist genetic clinics should discuss with women who have not had breast cancer, but are at high or moderate risk of developing it, the absolute risks and benefits of all options for preventive drug therapy. This should include the side effects of drugs, the extent of risk reduction and the risks and benefits of alternative approaches, such as risk-reducing surgery and surveillance. They should also give the women written information on these issues.
• Premenopausal women at high risk of breast cancer are offered a five-year course of tamoxifen, unless they have a past history of breast cancer or may be at increased risk of thromboembolic disease (disease caused by blood clots such as stroke) or endometrial cancer.
• Postmenopausal women without a uterus and at high risk of breast cancer are offered a five-year course of tamoxifen, unless they have a past history of breast cancer or may be at increased risk of thromboembolic disease or they have a past history of endometrial cancer.
• Postmenopausal women with a uterus and at high risk of breast cancer are offered either tamoxifen or raloxifene for five years, unless they have a past history or may be at increased risk of thromboembolic disease or endometrial cancer.
• Doctors can consider the same drug treatments in women in the three groups above who are at moderate (rather than high) risk of developing breast cancer.
• Women who were at high risk of breast cancer but have had a bilateral mastectomy are not offered tamoxifen or raloxifene.
• Treatment with tamoxifen or raloxifene is not continued for longer than five years.
• Women are informed that they should stop tamoxifen at least two months before trying to conceive and six weeks before elective surgery.

Do these drug treatments carry the risk of side effects?

Yes. Like all drug treatments both tamoxifen and raloxifene can cause side effects.

The most common side effects of tamoxifen are menopausal-type symptoms, such as:

• hot flushes and sweats
• vaginal problems such as itching
• hair loss
• nausea and vomiting
• tiredness
• aching joints and bone pain
• headaches
• blood clots (thromboembolism)

Common side effects of raloxifene include:

• hot flushes
• flu-like symptoms such as headache, sore throat and joint pain
• leg cramps
• gallstones

What other care does the guideline discuss?

As well as risk assessment, surveillance and preventive drug treatment, the guideline does discuss risk reducing surgery such as bilateral mastectomy (removal of both breasts) and breast reconstruction surgery.

This is the type of surgery that the actress Angelina Jolie announced she had undergone after genetic testing showed that she was at high risk of developing breast cancer. The NICE guideline notes that bilateral mastectomy is appropriate only for a small proportion of women who are from high-risk families.

The guideline also includes recommendations on less radical approaches to risk reduction in women with a family history of breast cancer. This includes informing women about factors that could increase their risk of breast cancer, such as taking the oral contraceptive pill in women aged over 35, taking hormone replacement therapy, drinking alcohol, or being overweight.

NICE also recommends that women with a family history of breast cancer:

• breastfeed whenever possible
• avoid smoking

Further details of these recommendations are available in the full guideline that can be accessed online at the NICE website