The Optimal Duration and Selection of Adjuvant Endocrine Therapy for Breast Cancer: How Long Is Enough?

Abstract

Women with estrogen receptor (ER)+ early breast cancer (BC) are at continuing risk of relapse up to at least 15 years after diagnosis, despite being on adjuvant endocrine therapy for approximately 5 years. Extended adjuvant endocrine therapy with an aromatase inhibitor (AI) after 5 years of tamoxifen further reduces the risk of recurrence in postmenopausal women. More recently, continuing tamoxifen for 10 years has also been shown to further reduce the risk of recurrence compared with 5 years. There are no direct comparative data on the relative merits of extended tamoxifen compared with an AI; indirect evidence suggests that an AI may have increased efficacy but a greater adverse effect on quality of life. Results are awaited on the need for continuing front-line adjuvant AIs for more than 5 years. The next challenge is to determine which patients will benefit from this long-term treatment. Currently, tumor size, nodal involvement, and gene expression profile as measured by the PAM50 Risk of Recurrence (ROR) score have all been shown to have prognostic significance for late recurrence beyond 5 years.KEY POINTSWomen with early-stage estrogen receptor (ER)+ breast cancer have a continuing risk of relapse that extends up to at least 15 years despite the use of adjuvant therapy.Recent evidence shows that tamoxifen for up to 10 years in patients with ER+ BC further reduces recurrence and BC mortality compared with 5 years. The additional gain only emerges after 10 years.There is also strong evidence in postmenopausal women that extended adjuvant endocrine therapy with an aromatase inhibitor (AI) after approximately 5 years of tamoxifen also further reduces the risk of recurrence and improves survival, at least in those with node-positive disease. There are no direct comparative data on the relative merits of extended tamoxifen versus an AI.Results are awaited on the need for continuing front-line adjuvant AIs for more than 5 years, but circumstantial evidence suggests that there will probably be further benefit.An important challenge is to determine which patients will benefit from this long-term treatment. Currently, tumor size, nodal involvement, and gene expression profile as measured by the PAM50 Risk of Recurrence score have all been shown to have prognostic significance for late recurrence beyond 5 years.