Tamoxifen Therapy for 10 Years versus 5 Years

Chicago—Patients who took tamoxifen for 10 years had a reduced disease recurrence and breast cancer mortality compared with a group receiving the drug for 5 years, according to a randomized, phase 3 trial that began >20 years ago. The benefit occurred later in the treatment period, usually at 7 years or beyond for the recurrence reduction and after 10 years for the reduced risk of death.

Richard G. Gray, MD, PhD, the study’s lead author, presented the data during the plenary session at the ASCO meeting. Cancer Research UK and the UK Medical Research Council supported the study.

Dr. Gray said the aTTom (Adjuvant Tamoxifen Treatment Offers More) study as well as another international sister trial called ATLAS (Adjuvant Tamoxifen: Longer Against Shorter) focused on randomizing at least 20,000 women to receive 5 or 10 years of tamoxifen therapy and then follow them for at least 15 years. Results of the ATLAS trial were recently published in The Lancet [2013;381(9869):805-816].

Dr. Gray noted that patients need at least 10 years of tamoxifen therapy to achieve the full benefit of treatment. In a meta-analysis of 20 trials published in The Lancet [2011;378(9793):771-784], patients who received 5 years of tamoxifen therapy had a significant reduction in recurrent cancer and mortality compared with patients who did not receive tamoxifen.

“This is a very effective treatment,” Dr. Gray said.

Although the effects of tamoxifen persisted after 5 years, 33% of patients who took tamoxifen for 5 years had recurrent disease within 15 years of stopping treatment. The authors in this study wanted to know if expanding the therapy for 10 years would reduce the recurrence.

Between 1991 and 2005, the authors in the aTTom study randomized 6953 women in the United Kingdom who had already received 5 years of tamoxifen to continue for another 5 years or discontinue treatment.

After 15 years of follow-up, there were 580 recurrences among patients taking 10 years of tamoxifen therapy compared with 672 recurrences in the 5-year group (risk reduction [RR], 0.85; 95% confidence interval [CI], 0.76-0.95; P=.003). For years 5 and 6 of treatment, there was no difference between the groups, but, starting in year 7, patients who continued on tamoxifen had a significant decrease in recurrence compared with the group stopping treatment.

In addition, there were 392 breast cancer deaths in the 10-year tamoxifen group compared with 443 deaths in the 5-year group (RR, 0.85; 95% CI, 0.77-1.01; P=.05). There was no difference in mortality early in the treatment period, but, after year 10, patients who took tamoxifen for 10 years had a significant reduction in breast cancer mortality.

During the study, there were also 481 deaths in the 10-year group and 487 deaths in the 5-year group that occurred without breast cancer recurrence. For all-cause mortality, there were 885 deaths in the 10-year group and 939 deaths in the 5-year group (P=.20), although there were significantly fewer deaths in year 10 and beyond after treatment (P=.016).

For the individual aTTom and ATLAS studies and when the trials were combined, there were no significant differences in breast cancer mortality from years 5 to 9 of treatment. However, there was a significant difference after 10 years of treatment in the aTTom (P=.007), ATLAS (P=.002), and combined (P=.00004) trials. The ATLAS study enrolled 11,646 patients.

Dr. Gray noted that in the aTTom study, there was a significant increase in endometrial cancers (P<.0001) and endometrial cancer death (P=.02) among patients taking 10 years of tamoxifen therapy compared with the 5-year group.