Breast cancer drugs set for preventative use

Almost all of the newspapers and their websites are leading with the news that the National Institute for Health and Clinical Excellence (NICE) has published draft guidelines recommending that women with a high risk of familial breast cancer should be offered preventative drug treatments.

The news is based on draft guidelines released by NICE for the care of women at risk of developing breast cancer that runs in families (familial breast cancer).

The new draft guidelines update the 2006 guidelines, and include new recommendations on genetic testing and monitoring of the disease. 

New proposals are also included for the use of preventative therapies for people who don't have breast cancer, but who are considered to be at high risk of developing the disease because of a strong family history of breast or ovarian cancer, and other specific cancers.

The recommendation attracting most media coverage is that women with a high risk of developing familial breast cancer are given drug treatments such as tamoxifen to lower their risk of developing the disease. This would be the first time in the UK that a non-surgical preventative treatment approach would be used to tackle familial breast cancer.

However, the guidelines are still in the early stages of the consultation process, which is taking place between January 2013 and February 2013. The recommendations may undergo changes prior to final publication, which is set for June 2013.

What is familial breast cancer?

Breast cancer is the most common cancer in women in the UK, affecting one in eight women over the age of 50. Familial breast cancer typically occurs in people with an unusually high number of family members affected by breast or ovarian cancer, as well as a few other specific cancers or cancer patterns. It is also known as hereditary breast cancer.

But even if a person has one or more relatives who have or have had breast cancer, it does not necessarily mean that breast cancer runs in their family. As breast cancer is common, more than one woman in a family may develop it by chance. NICE estimate that less than 1% of women are at high risk of developing familial breast cancer.

When breast cancer does run in the family, it may be caused by a fault in one of the genes known to be linked with breast cancer, such as the BRCA1, BRCA2, TP53 or PTEN genes.

Because of the differences in the risk of developing breast cancer, people whose family history suggests familial breast cancer may need different management to people without a strong family history.

What new recommendations have NICE made about familial breast cancer?

The new NICE guidelines include recommendations for women without breast cancer but who are considered to be at high risk of familial breast cancer.

These include:

• the offer of preventative drug therapy (either tamoxifen or raloxifene) for five years to post-menopausal women at high risk of developing breast cancer, unless they have a past history of blood clots or cancer of the uterus – NICE also recommend offering such treatment as preventative therapy for women at moderate risk on a case-by-case basis
• annual mammogram screening for women aged 40 to 49 years judged to be at moderate risk of breast cancer 
• annual mammogram screening for women aged 40 years and older considered to be at high risk of breast cancer
• which groups of women should be offered annual MRI (magnetic resonance imaging) monitoring (according to age and specific gene mutations) 

It also makes recommendations for women who have previously been diagnosed with breast cancer who have a family history of breast or related cancers. These include:

• annual MRI monitoring for all women aged 30 to 49 years with a personal history of breast cancer who are at high risk of developing cancer in the other breast, or who have a particular gene mutation
• annual mammogram monitoring for all women aged 50 to 69 years with a personal history of breast cancer who are at high risk of developing cancer in the other breast, or who have a particular gene fault

Recommendations about when genetic testing should be offered are also outlined in the new draft guidelines.

What evidence are these recommendations based on?

The NICE recommendations are based on the best available evidence and the consensus of a group of experts. They are developed using transparent, recognised methods.

The guideline development group has made recommendations based on the benefits and harms of interventions while taking the quality of the underpinning evidence into account. They say that throughout the document, wording has been chosen to reflect the strength of their recommendations.

What drugs are being proposed to prevent familial breast cancer in high-risk individuals?

NICE currently proposes that post-menopausal women considered at high risk of breast cancer should be offered preventative drug therapy with tamoxifen (brand names Nolvadex, Istabul or Valodex) and raloxifene (brand name Evista). This advice is for women who don't have a personal history of blood clots or cancer of the uterus.

The draft guidelines state that at the time of writing (January 2013), neither of these drugs have a current UK license for this specific use, so prescribing them in these situations would be "off-label". They report this is recommended where there is "good evidence to support that use". 

Do these drugs have any side effects and safety concerns?

All drugs have potential side effects, which can range from mild and moderate to severe. The recommendations made in the draft guidelines have outlined circumstances when tamoxifen and raloxifene should not be offered or considered.

Should these drugs be recommended in the final guidance publication, potential side effects would need to be discussed with the patient before they are prescribed, and all people taking the drugs would need to be monitored for any adverse (side) effects.

The most commonly reported side effects of tamoxifen, affecting more than one in 10 people who take the medication, are:

• vaginal discharge, itching or bleeding
• hot flushes

The most commonly reported side effects of raloxifene are:

• leg cramps
• hot flushes
• flu-like symptoms such as joint and muscle pain

The side effects of both drugs often improve with time as the body gets used to the effects of the medication.

When is this guidance likely to come into force?

NICE is consulting on this draft guidance until February 2013. The final guidelines are set for publication in June 2013. It is likely that the draft guidelines will undergo changes prior to final publication.