“Hormone treatments can cut breast cancer rates in at-risk women by 38%,” reports the Daily Mirror.
The news, covered by much of the media, is based on research into selective oestrogen receptor modulators (SERMs), a class of drug that binds to oestrogen receptors in breast cells and elsewhere.
The study making today’s news suggests that SERMs could be effective for preventing breast cancer. Researchers combined the results of several studies that had compared SERMs with other drugs in women without breast cancer.
Most of the trials recruited women who were either at high risk of breast cancer or who had osteoporosis.
Researchers found that SERMs reduced the incidence of breast cancer during 10 years of follow-up.
The drugs also seemed to reduce the risk of breast cancer both while women were receiving the drugs and after treatment had been stopped. The drugs had no effect on risk of death due to breast cancer or death due to any other cause.
Although these results are promising, it is important to remember that none of these drugs are currently licensed for the prevention of breast cancer in the UK.
These drugs also have side effects, meaning that they would not be suitable for everyone. Women receiving SERMs were at increased risk of cancer of the uterus and of blood clots (known risks of these drugs).
Guidelines about familial breast cancer for doctors is currently being updated to include new (provisional) recommendations on using tamoxifen to prevent breast cancer in women at high risk of the disease.
Where did the story come from?
The study was carried out by an international team of researchers participating in the Selective Oestrogen Receptor Modulator Chemoprevention of Breast Cancer Overview Group. It was funded by Cancer Research UK.
The study was published in the peer-reviewed medical journal, The Lancet.
This article was open-access, meaning that it is available for free from the journal’s website.
The news was well reported in the media, with some of the news stories acknowledging the observed side effects associated with these drugs and that they are not currently licensed for the prevention of breast cancer.
What kind of research was this?
This was a systematic review and meta-analysis of data from individual participants in randomised controlled trials. It aimed to assess the effectiveness of selective oestrogen receptor modulator drugs (SERMs) for preventing breast cancer.
A systematic review and meta-analysis of randomised controlled trials combines all the known information found in individual trials. It gives an overall picture of the effectiveness of a drug or intervention, and as such, it provides the highest level of evidence for an intervention.
What did the research involve?
The researchers performed a systematic search of databases of published trials to identify trials that had analysed the effectiveness of SERMs for preventing breast cancer. They identified nine randomised trials that compared SERMs with placebo or another drug in women without breast cancer, and that followed women up for at least two years.
The trials examined four SERMs. These were tamoxifen (licensed in the UK for the treatment of oestrogen receptor positive breast cancer), raloxifene (licensed for the treatment and prevention of osteoporosis in postmenopausal women) and lasofocifene and arzoxifene (two osteoporosis drugs not currently licensed in the UK). The nine trials comprised:
- four trials that assessed 20mg per day tamoxifen versus placebo for at least five years in healthy women who were mostly at increased risk of breast cancer
- two trials that investigated raloxifene versus placebo in postmenopausal women who had either osteoporosis or had risk factors for, or established, coronary heart disease. An additional trial compared raloxifene to tamoxifen in women at increased risk of developing breast cancer.
- one trial that compared lasofoxifene at two different doses with placebo in postmenopausal women with osteoporosis
- one trial that compared arzoxifene with placebo in postmenopausal women with osteoporosis
Women received treatment for between four and eight years, and follow-up in some trials continued after treatment had finished.
The researchers obtained data for individual participants, and combined the data to determine the overall effectiveness of SERMs for preventing breast cancer.
The prime outcome that the researchers were interested in was the incidence of breast cancer during 10 years of follow-up. They also investigated:
- incidence of breast cancer in the first five years (when treatment was given) and in years five to 10 (when treatment had generally stopped)
- the incidence of different types of breast cancer
- the incidence of other cancers
- the incidence of blood clots, cardiovascular events, fractures, cataracts and death from any cause
What were the basic results?
The nine trials had a total of 83,399 women participants, who had been followed up for 65 months (5.4 years) on average.
The effect of selective oestrogen receptor modulators on breast cancer
The researchers found that SERMs significantly reduced the risk of all types of breast cancer by 38%. The 10-year cumulative incidence of all breast cancers was estimated to be 6.3% in the control groups and 4.2% in the groups receiving a SERM. The researchers calculated that this means that if 42 women were treated with a SERM, one case of breast cancer would be prevented in the first 10 years of follow-up.
The reduction in risk of all breast cancers was larger in the first five years of follow-up, when treatment was given (42% reduction) than in years five to 10, after treatment had stopped (25% reduction).
SERMs reduced the risk of oestrogen receptor (ER) positive breast cancer from 4.0% to 2.1% over 10 years (a 51% reduction in risk), but did not significantly affect the risk of ER negative breast cancers.
SERMs also reduced the risk of what is called ‘ductal carcinoma in situ’. This is an early type of breast cancer where the cancer is confined to the milk ducts and has not yet spread to the surrounding breast tissue.
When the trials were analysed by SERM, it was found that:
- tamoxifen significantly reduced the risk of all breast cancers by 33% over 10 years of follow-up compared with placebo, mainly due to a reduction in ER positive breast cancer
- raloxifene also significantly reduced the risk of all breast cancers (by 34%) over 10 years of follow-up compared with placebo, again mainly due to a reduction in ER positive breast cancer
- the trials of lasofoxifene and arzoxifene only had follow-up results for years 0 to five. Lasofoxifene (0.5mg) and arzoxifene also reduced all breast cancers and ER positive cancers
The effect of selective oestrogen receptor modulators on other outcomes
- Women receiving a SERM had a significantly higher rate of cancer of the uterus (womb) than those given a placebo, although the effect seemed to be limited to during the first five years (during treatment) and to tamoxifen. There was no difference in the incidence of other cancers.
- Women receiving a SERM were also at increased risk of blood clots compared to women receiving placebo.
- Women receiving SERMs were at decreased risk of fractures (although no effect was seen with tamoxifen when this was analysed on its own).
- There was no significant difference in the risk of cardiovascular events or cataracts.
However, SERMs had no effect on the rates of death due to breast cancer, or death from any cause.
How did the researchers interpret the results?
The researchers conclude that selective oestrogen receptor modulators “significantly reduce the risk of all breast cancer in high-risk and average-risk women who do not have the disease, which is due to a reduction in ER positive invasive breast cancer”. The researchers also note that, “benefits were noted during the active treatment period, but also after treatment was completed”.
This study has found that selective oestrogen receptor modulators could be effective for preventing breast cancer – in particular oestrogen receptor positive cancers. SERMs reduced the incidence of breast cancer during 10 years of follow-up, and the drugs seemed to reduce the risk of breast cancer both while women were receiving the drugs and after treatment had been stopped. There was no difference in deaths due to breast cancer or deaths due to any cause between women taking selective oestrogen receptor modulators or placebo.
Although these results are promising, it is important to remember that none of these drugs are currently licensed for the prevention of breast cancer in the UK. It’s important to note that SERMs also have side effects, meaning they would not be suitable for everyone. Women receiving SERMs in these studies were at increased risk of cancer of the uterus and of blood clots. Blood clots such as deep vein thrombosis (DVT) are already a well-recognised risk of taking SERMs. SERMs may also stimulate an overgrowth in the cellular lining of the uterus, which could lead to cancerous change.
The National Institute for Health and Care Excellence (NICE) is currently updating its clinical guideline on familial breast cancer, which includes new, provisional recommendations on the use of tamoxifen for prevention of breast cancer to women at high risk. Some of the media coverage may have given the impression that these drugs will revolutionise the care of women at risk of breast cancer. Inevitably, even if these drugs are approved for this use, women and their doctors will need to consider the risks that they pose as well as the benefits they bring before deciding on the best treatment options.