Meta-Analysis Furthers Evidence of Tamoxifen’s Efficacy

August 22, 2011

Advances in the treatment for breast cancer have allowed for better outcomes and decreased mortality rates. Tamoxifen, the oldest and most frequently prescribed selective estrogen receptor modulator approved by the US Food and Drug Administration, has shown great efficacy, and studies of tamoxifen treatment lasting 5 years now have follow-up efficacy data that go past one decade. To better understand the evidence, the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) conducted a meta-analysis of 20 trials to ascertain the protective effects of tamoxifen in reducing recurrence and death ratios.

Advances in the treatment for breast cancer have allowed for better outcomes and decreased mortality rates. Tamoxifen, the oldest and most frequently prescribed selective estrogen receptor modulator approved by the US Food and Drug Administration, has shown great efficacy, and studies of tamoxifen treatment lasting 5 years now have follow-up efficacy data that go past one decade. To better understand the evidence, the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) conducted a meta-analysis of 20 trials to ascertain the protective effects of tamoxifen in reducing recurrence and death ratios.

In their meta-analysis, the EBCTCG researchers looked at such factors as treatment, age, menopausal status, tumor diameter, grade, spread to locoregional lymph nodes, and any estrogen receptor or progesterone receptor measurements. Follow-up data were available upon recurrence of breast cancer, other cancer, or death. Most of the trials in the meta-analysis lasted 5 years, but some studies lasted 4 years, and one study allowed for rerandomization at 2 years to include progression to the 5-year mark or discontinuation in study. All studies consisted of an active group and a control group. Overall, the EBCTCG group looked at outcomes for 21,457 women.

The EBCTCG researchers found that tamoxifen reduced the recurrence rate by half in patients with estrogen receptor–positive disease between years 0 and 4 and reduced the recurrence rate by one-third between years 5 and 9. They found little effect after year 10. Based on this data, an overall average 39% reduction in recurrence was found. However, the researchers failed to find any effect on recurrence in estrogen receptive–poor disease.

Although they found a strong association between estrogen receptor and progesterone receptor status (progesterone receptor was positive in 76% of estrogen receptor–positive cases), progesterone receptor status did not significantly predict response. The EBCTCG researchers found that tamoxifen had an additive protective factor when chemotherapy was used, conferring about 25% further reduction in 10-year recurrence risk. Similarly, they found a greater reduction in risk for recurrence in studies with higher dosages of tamoxifen, but this benefit did not translate into greater reductions in breast cancer mortality. Women of all ages showed benefits of tamoxifen. The researchers noted a slightly greater reduction at older ages, but this finding was not significant.

“Our meta-analyses show a definite and substantial protective effect even at ER [estrogen receptor] measurements of only 10-19 fmol/mg, and show that on average in all women with ER-positive disease full compliance with 5 years of adjuvant tamoxifen would reduce the breast cancer mortality rate during the first 15 years after the start of treatment by at least a third, compared with no adjuvant endocrine therapy,” the researchers concluded.

More Information

National Cancer Institute: TamoxifenTamoxifen May “Cure” ER-Positive Breast Cancer

References:

Reference
Early Breast Cancer Trialists’ Collaborative Group.Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials.  Lancet. 2011 Jul 28 [Epub].