Status of adjuvant endocrine therapy for breast cancer

Abstract

Adjuvant endocrine therapy reduces the risk of recurrence and death from breast cancer in women with hormone receptor-positive early breast cancer.Tamoxifen has been the standard therapy for decades, and this is still the case for pre-menopausal women.Ovarian suppression is of similar efficacy but currently there is no strong evidence for adding this to tamoxifen and the additional morbidity can be considerable. Results from two important trials addressing this issueare imminent. In post-menopausal women, aromatase inhibitors (AIs) (letrozole, anastrozole, or exemestane)are superior to tamoxifen in preventing recurrence but only letrozole has been shown to improve survival. The main gain is against high-risk cancers, and tamoxifen gives very similar benefit for low-risk disease. Traditionally, treatment has been given for around 5 years, but many women remain at risk of relapse for 10 years or more.The AIs, and more recently tamoxifen, have been shown to reduce further the risk of late recurrence in women still in remission after 5 years of tamoxifen if given for a further 5 years. The comparative benefits of these two options and the selection of patients most likely to benefit from long-term adjuvant endocrine therapy are important topics for further research, as is the optimum duration of AI therapy started upfront.

Figure 1

Adjuvant endocrine therapy history: the first key steps. The first steps in the evolution of endocrine therapy are presented. *In seven of these trials, the ovarian ablation (OvA) and control groups received no routine cytotoxic chemotherapy, in one there were random assignments both for cytotoxic therapy and for OvA in a ‘factorial’ design, and in four both groups were scheduled to receive a common cytotoxic chemotherapy regimen (after OvA, in those allocated this treatment). BC, breast cancer; BD, bis die (twice daily); CRC, Cancer Research Campaign; EBC, early breast cancer; EBCTCG, Early Breast Cancer Trialists’ Collaborative Group; ER, estrogen receptor; i.v., intravenously; NATO, Nolvadex Adjuvant Trial Organization; NSABP, National Surgical Adjuvant Breast and Bowel Project; OS, overall survival; OvS, ovarian suppression; RFS, recurrence-free survival; yr, year (s).