Among postoperative therapies for early breast cancer, endocrine therapy is responsible for the greatest reduction in the risk of recurrence and death. Following resection of hormone receptor–positive breast cancer, adjuvant endocrine therapy reduces the risk of local recurrence, distant metastasis, and contralateral breast cancer. Currently new medical oncology treatments described as targeted therapies are improving outcomes in a variety of malignancies. Tamoxifen treatment for breast cancer represents the first successful application of a targeted therapy, where the drug targets the estrogen receptor (ER) on any residual tumor cells. Tamoxifen is described as a selective estrogen receptor modulator (SERM) because of its varying effects in different tissues, where it may act as an antagonist (eg, breast) or an agonist (eg, uterus).
The most recent Early Breast Cancer Trialists' Collaborative Group (EBCTCG) Oxford overview analysis was published in 2005. This analysis found that among women with ER-positive tumors who were randomized to receive 5 years of adjuvant tamoxifen, the annual breast cancer recurrence rate was almost halved (41% proportional risk reduction) and the breast cancer mortality rate was reduced by one-third (34% proportional risk reduction) compared with those who did not receive tamoxifen.1 These benefits were observed across all age groups, regardless of the use of chemotherapy, and in both node-negative and node-positive disease. While the relative (proportional) risk reduction is similar for these different patient groups with ER-positive tumors, the absolute benefit from treatment with tamoxifen is greater for women at higher risk for relapse (Table 86-1).
Table 86-1 Benefit from 5 Years of Adjuvant Tamoxifen in ER-Positive (or Unknown) Breast Cancer ||Download (.pdf)
Table 86-1 Benefit from 5 Years of Adjuvant Tamoxifen in ER-Positive (or Unknown) Breast Cancer
|Absolute Difference in Recurrence at 10 Years*||Absolute Difference in Mortality at 10 Years*|
|Node-positive breast cancer||∼15%||∼12%|
|Node-negative breast cancer||∼12%||∼5%|
The EBCTCG overview analysis also shows that for women who were randomized to receive adjuvant tamoxifen for 5 years, there is evidence of a protective carry-over effect with continued divergence of the risk of recurrence curves after tamoxifen treatment has been ceased during years 6 to 10. The mortality curves for patients treated with and without tamoxifen continue to diverge with 15 years of follow-up, indicating that the benefits are substantial and persistent. In women with ER-positive disease, adjuvant tamoxifen also reduces the risk of contralateral breast cancer by about one-third.
Recurrences after surgery for early breast cancer are not confined to the first 5 years, and this is particularly true for hormone receptor–positive breast cancer. For hormone receptor– negative breast cancer, recurrences occur predominantly during the first 5 years after surgery, whereas for hormone receptor–positive breast cancer there remains ...