Minimizing early relapse and maximizing treatment outcomes in hormone-sensitive postmenopausal breast cancer: efficacy review of AI trials

Abstract

Breast cancer is one of the leading causes of cancer-related deaths in women. Regardless of prognosis, all women with breast cancer are at risk for early recurrence. Nearly 50% of early recurrences occur within 5 years of surgery, and they peak at 2 years after surgery in women treated with adjuvant tamoxifen. Most early recurrences are distant metastases, which strongly correlate with increased mortality. Treatments that mitigate the risk of early distant metastases (DM) are, therefore, likely to improve overall survival in women with early breast cancer (EBC). Aromatase inhibitors (AIs)--anastrozole, letrozole, and exemestane-have been investigated as alternatives to tamoxifen for adjuvant treatment of hormone receptor-positive (HR+) EBC in postmenopausal women (PMW). AIs are better at minimizing risk of early relapse compared with tamoxifen. However, it is not clear if preferential use of AIs over tamoxifen will benefit all PMW with HR+ EBC. The ability to subtype HR+ breast cancer on the basis of biomarkers predictive of response to AIs and tamoxifen would likely be key to determining the most beneficial hormonal treatment within patient subpopulations, but this process requires thorough investigation. Until then, adjuvant therapies that provide the greatest reduction in risk of DM should be considered for all PMW with HR+ EBC. This article reviews the clinical trials of AI adjuvant therapies for hormone-sensitive breast cancer, particularly in the context of how they compare with tamoxifen in minimizing the risk of relapse, occurrence of DM, and breast cancer-related deaths.

Fig. 1

Prevalence of distant metastases at 2-year peak of overall recurrences [4]

Fig. 2

Types of adjuvant trials. AI aromatase inhibitor

Fig. 3

Absolute reduction in overall recurrences and distant metastases in the a Arimidex, Tamoxifen Alone, or Combination trial (hormone receptor-positive patients) at 2.5 years [3] and b Breast International Group 1-98 at 2 years [6]. ANA anastrozole; LET letrozole; TAM tamoxifen

Fig. 4

Breast International Group 1-98 schema/analysis. CT chemotherapy; ITT intent-to-treat