Tamoxifen 'should be taken for full five years'

Behind the Headlines

Tuesday March 22 2011

Breast cancer returned in fewer women who took a full 5-year course of Tamoxifen

“Women boost their chances of surviving breast cancer if they complete their full five-year course of tamoxifen,” reported the Daily Mirror. The newspaper said that many women stop taking it after two years due to side effects, but a study has found that breast cancer returned in 46% of women who stopped taking it early, compared to 40% who completed the course.

This study compared the survival rates and time without an “event”, such as tumour recurrence, in women who had taken tamoxifen for early stage breast cancer for five years compared to those who had taken it for two.

After 15 years, women in the five-year treatment group were less likely to have had tumour recurrence or a cardiovascular event than those in the two-year group.

This research supports recommendations that tamoxifen should be taken for five years for breast cancer. This is an important finding to highlight, as it is estimated that as many as half of women on tamoxifen stop taking it early. Women who are having problems taking tamoxifen should consult their doctors who may be able to help them.

 

Where did the story come from?

The study was carried out by researchers from Cancer Research UK and University College London Cancer Trials Centre. Funding was provided by Cancer Research UK. The study was published in the (peer-reviewed) Journal of Clinical Oncology.

This study was well described by BBC News and the Daily Mirror.

What kind of research was this?

This was a survival analysis using data from a randomised controlled trial of tamoxifen in women around the time of their menopause who had early breast cancer. It compared survival rates of women who stopped taking tamoxifen after two years with those of women who continued to take the drug for the full five-year period advised. The women were followed-up for an average (median) of 10 years, but a quarter were followed for about 14 years, and some as long as 18 years after the start of the trial.

Tamoxifen is a tablet used to treat breast cancer. It blocks the effect of oestrogen on tumour cells and is particularly effective for women with tumours whose growth is promoted by oestrogen.

The researchers say that an overview of previous research found that two years of tamoxifen therapy had far less favourable outcomes than taking the therapy for five years. Two years of tamoxifen therapy was associated with a 29% reduction in cancer recurrence and a 17% reduction in deaths over 10 years. This was compared with a 47% reduction in cancer recurrence and a 26% reduction in deaths with taking the drug for five years.

The present research reports the longer-term follow-up of one of the largest trials comparing five years of tamoxifen with two years of tamoxifen.

 

What did the research involve?

The study recruited women who were over 50 and had early breast cancer in one breast between 1987 and 1997 from 71 cancer centres internationally. Of 3,449 patients, 1,724 women were assigned to receive tamoxifen for two years, and 1,725 for five years.

The women were followed for up to 18 years after they had stopped their trial treatment. Data on new tumours, recurrences, cardiovascular events and deaths were recorded. The researchers focused on “event-free survival” (EFS), which was defined as the time between starting tamoxifen until tumour recurrence in the same place in the breast, or the appearance of a new tumour, or death.

A quarter of the women were followed for more than 14 years, but the median follow-up was 10.1 years.

 

What were the basic results?

The participants had different follow-up times, for example, because some of the women died (from cancer or non-cancer related causes). The researchers analysed the effects of the different lengths of treatment by examining the number of ‘person-years’ each group had of EFS.

Person-years is a calculation of the number of participants multiplied by the number of years each person is followed-up, and it allows the statistical analysis to take into account different length of follow-up times. In this case, the analysis corresponded to a total of 37,035 person-years for the 3,449 participants. Fifteen women didn’t complete the course in the two-years group, and 202 didn’t complete it in the five-years group. In the total population, there were 1,868 EFS events, 1,577 deaths, 1,103 recurrences (876 of the recurrences were followed by death), 755 deaths from breast cancer and 621 cardiovascular events (including 236 deaths).

The researchers calculated the risk of event-free survival, recurrence, breast cancer mortality and the risk of death after recurrence for the women who had received tamoxifen for five years relative to women who had received tamoxifen for two years.

This analysis showed that women who received tamoxifen for five years had:

  • an 11% reduction in EFS event rate (Hazard ratio, HR, 0.89, 95% CI 0.81 to 0.97)
  • an 8% reduction in death rate (HR, 0.92, 95% CI, 0.84 to 1.02) (not statistically significant)
  • a 17% reduction in the risk of recurrence (HR, 0.83, 95% CI 0.74 to 0.94)
  • a 9% reduction in the chance of death as a result of breast cancer (HR 0.91, 95% CI 0.79 to 1.06) (not statistically significant)
  • a 14% reduction in the risk of death after recurrence (HR 0.86, 95% CI 0.76 to 0.99) (borderline statistical significance)

The researchers then looked at how the risks were affected over time. They found that 15 years after starting tamoxifen, there were 5.8 fewer experiences of cancer recurrence per 100 women who took it for five years, than those who took it for two years. Women who had taken tamoxifen for five years were 30% less likely than women who had taken the drug for two years to develop a tumour on their other breast (HR, 0.70; 95% CI, 0.48 to 1.00) borderline significance.

Other differences between the groups after 15 years were:

  • 68% of women in the two-year group and 63% of women in the five-year group had either died, suffered a recurrence or a new tumour
  • 8% of women in the two-year group and 6% of women in the five-year group had a tumour in the opposite breast
  • 46% of women in the two-year group and 40% of women in the five-year group had breast cancer recurrence

Analyses showed no association between age at the start of tamoxifen treatment and event-free survival or overall survival. Also, the effect of five-years tamoxifen was not affected by menopausal status. However, in women aged 50 - 59 years there was a 35% reduction in cardiovascular events in those taking tamoxifen for five years relative to two years (p=0.005) and a 59% reduction in death as a result of a cardiovascular event. In older women, there was no difference in risk of cardiovascular events between those who had received longer or shorter treatment with tamoxifen.

 

How did the researchers interpret the results?

The researchers said that “15 years after starting five years of tamoxifen, there was a clear reduction in the risk of recurrence and of developing cancer in the opposite breast. Furthermore, there was a reduction in cardiovascular disease and mortality, particularly among women aged between 50 to 59 years”.

The researchers suggest that women should be encouraged to continue with tamoxifen therapy for the current recommended target duration of five years.

 

Conclusion

The study showed that taking tamoxifen for the full recommended five years is beneficial in terms of cancer recurrence and cardiovascular health. This is an important finding to highlight, as many women stop taking tamoxifen before this time. The researchers say that although most (88%) of the women in the five-year group took the medication for the full time in this study, other studies have shown that in real life many women stop early (they cited that other studies had estimated that almost half of women stopped taking tamoxifen by five years).

Probable reasons for this include either treatment-related side effects (which are common), older age (over 80 years), or that women may feel that they can safely stop taking the drug because their cancer status has not appeared to change for two or three years.

This research supports the recommendation that women should continue to take tamoxifen for the five-year period. As well as reducing cancer recurrence, the drug also appears to prevent new/second tumours appearing in the opposite breast, and protects against cardiovascular disease.

Women who find it problematic to continue taking tamoxifen should consult their doctors to find ways of helping them do so.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Women risk cancer returning by stopping Tamoxifen early. BBC News, March 22 2011

Doctors urge breast cancer patients to take tamoxifen for full five years. Daily Mirror, March 22 2011

Links to the science

Hackshaw A, Roughton M, Forsyth S et alLong-Term Benefits of 5 Years of Tamoxifen: 10-Year Follow-Up of a Large Randomized Trial in Women at Least 50 Years of Age With Early Breast Cancer. Journal of Clinical Oncology 2011, Published online before print March 21

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