Stopping tamoxifen 'ups breast cancer death risk'
“Hundreds of women are dying needlessly every year as they stop taking breast cancer drugs because of the unbearable side effects,” reports The Daily Telegraph.
The news is based on a study looking at whether women prescribed tamoxifen after breast cancer surgery took the drug as prescribed (adherence).
Researchers wanted to compare the cost-effectiveness of tamoxifen after breast cancer surgery for women who were highly adherent with those whose adherence to treatment was low.
Researchers analysed data on just over 1,000 Scottish women prescribed tamoxifen to try and reduce risk of cancer recurrence. They found that women with low “adherence” (stopping or taking it irregularly) to tamoxifen had shorter time to cancer recurrence, increased medical costs, and poorer quality of life.
However, despite the headlines, we can’t tell why the women didn’t stick with their treatment. The reasons people stop taking potentially life-saving treatment are complex, and can be due to many factors, including psychosocial and health factors, as well as side effects.
Currently, women given tamoxifen after breast cancer surgery are advised to take it for five years, and the results of this study support this. The study authors suggest that it would be cost-effective for the health service to intervene to encourage women to continue taking tamoxifen daily for the whole five-year period.
Where did the story come from?
The study was carried out by researchers from the University of Glasgow, Imperial College Business School, the University of Dundee and Botswana International University of Science and Technology, and the University of Melbourne. It was funded by Breast Cancer Campaign. The study was published in the peer-reviewed British Journal of Cancer.
All the news reporting of this study reported that women didn’t take tamoxifen due to the ‘unbearable side effects’. It is not clear what this is based on, as the study did not investigate the reasons for low adherence (not taking medicine as it is prescribed). In fact, in their discussion the researchers report that “adherence behaviour of patients is a complex process determined by many factors”. These include patient characteristics, characteristics of the disease and treatment (which includes side-effects), the health-care system and service delivery.
What kind of research was this?
This was an economic evaluation. It aimed to determine the impact of adherence to tamoxifen (taking medicine as it is prescribed – in this case once per day for five years). Researchers wanted to better understand how cost-effective it is to prescribe tamoxifen after surgical treatment for breast cancer. They wanted to know how much less cost-effective it would be if women didn’t take the drug as advised.
Tamoxifen is a hormone therapy used to treat women who have “oestrogen receptor positive” breast cancer. In these women, the hormone oestrogen binds to these receptors, stimulating growth of the breast cancer cells. Tamoxifen works by binding to these receptors instead, stopping oestrogen from binding to them and therefore helping to prevent growth of the cancer.
Depending on the characteristics of the cancer, women may be given tamoxifen either before surgery to shrink the cancer to make it easier to remove (called “neoadjuvant” treatment), or after surgery to try and prevent the cancer from coming back (called “adjuvant” treatment). The current study investigated adjuvant use of tamoxifen (after surgery). When prescribed after surgical treatment, it is currently recommended that tamoxifen is taken for five years to try to prevent recurrence of breast cancer.
To look at the cost effectiveness of adjuvant tamoxifen, the researchers investigated levels of adherence among women prescribed adjuvant tamoxifen in Tayside, Scotland, over a 15-year period. They looked at how low adherence affected risk of recurrence of breast cancer, death, and medical costs. They then compared the cost-effectiveness of tamoxifen therapy between women with high and low adherence.
What did the research involve?
The researchers looked at the health records of women living in Tayside who were diagnosed and treated for breast cancer between January 1993 and December 2008. They included women diagnosed before the end of December 2000, who had surgical treatment for breast cancer, who were then prescribed tamoxifen, and who survived for 60 days after diagnosis (1,263 women).
Adherence to tamoxifen was investigated by examining the proportion of the expected treatment period (five years – or cancer recurrence or death if these occurred before the end of the five year period) that was covered by tamoxifen prescriptions. When less than 80% of the treatment period had prescriptions this was classified as low adherence.
The researchers also extracted information on:
- deprivation level (calculated based on postcode)
- presence of any other diseases
- tumour size
- whether the tumour had spread to the lymph nodes
- whether the tumour had metastasised (spread to other parts of the body)
- the “grade” (severity) of the tumour
- whether the tumour was oestrogen receptor positive
The researchers also looked at the women’s disease progress. They looked to see if the women had died (and if so what caused their death), and whether their cancer had recurred (and if so the type of recurrence).
This information was used to create a model that predicted lifetime disease progress and lifetime costs depending on tamoxifen adherence.
What were the basic results?
The study included 1,263 women. During the study, cancer recurred in 354 women, of whom 306 died due to breast cancer and 21 died from other causes. A further 198 women died from other causes, without recurrence.
Adherence was low in 475 women (38%). After controlling for menopausal status, social class, the presence of other diseases and other clinical characteristics, women were more likely to have low adherence if they were younger, had higher tumour stage, or had an oestrogen receptor-negative tumour.
Of the 475 women with low adherence, 127 had a recurrence (27%) and 63 died before recurrence (13%). Of the women with high adherence, 197 (25%) had a recurrence and 135 (17%) died before recurrence.
For women with low adherence to tamoxifen, the expected time until recurrence was reduced by 52.38%.
The researchers’ model found that high adherence reduced recurrence by 8.95% and deaths from breast cancer by 8.65%. Low adherence resulted in a loss of 1.32 life years, and 1.12 quality-adjusted life years (where time is adjusted for any disability that a person may have). Low adherence was associated with an added cost of £5,970 compared with high adherence, and the value of changing a woman from low adherence to high adherence was calculated to be £33,897 (assuming that each quality-adjusted life year is worth £25,000).
How did the researchers interpret the results?
The researchers concluded that “patients with low adherence have shorter time to recurrence, increased medical costs and worse quality of life. Interventions that encourage patients to continue taking their treatment on a daily basis for the recommended five year period may be highly cost-effective.”
This study has found that low adherence to tamoxifen therapy after surgical treatment for breast cancer results in poorer health outcomes and increased health costs. The current recommended treatment period for tamoxifen when used after breast cancer surgery is five years.
The reasons for low adherence were not explored in this study. Adherence is a complex issue, and is determined by many factors including patient factors (including other psychosocial and health issues), characteristics of the disease and response to treatment (including side-effects), and healthcare delivery.
It should be noted that, in this study, filled prescription records were used to monitor adherence. This has the disadvantage that we can’t tell if women actually took the medication. Also, poor adherence in this study included both women who took tamoxifen regularly but then stopped before the treatment period was over, and women who took tamoxifen for the whole treatment period but took it irregularly. Larger studies will be required to see if women who take tamoxifen regularly but for a shorter period than recommended have different outcomes from those who take tamoxifen for a longer period of time but at less regular intervals.
Although the authors of this study suggest that interventions encouraging women to continue taking tamoxifen daily for the whole of the recommended five–year period may be cost-effective, further research is required to find out what these interventions may be.