The original Tamoxifen Exemestane Adjuvant Multinational (TEAM) study found no significant differences for disease free survival (DFS) and overall survival (OS) at five years between exemestane monotherapy and sequential treatment (tamoxifen followed by exemestane), but there is still no universal agreement on optimal endocrine therapy. 

Now, the 10-year TEAM results have confirmed that both exemestane monotherapy and sequential therapy are acceptable, viable options for postmenopausal women with hormone-receptor positive (HR+) early breast cancer, European researchers noted. Additionally, an exploratory analysis suggests that higher estrogen receptor- (ER-) grade tumors may be more susceptible to exemestane therapy. They presented the results of the study and an exploratory analysis on Wednesday, December 7, during the San Antonio Breast Cancer Symposium. 

The primary endpoint was DFS at 10 years, analyzed by intent-to-treat. Secondary outcomes were OS and cumulative incidence of relapse. An explorative per protocol analysis for relapse-free survival (RFS) was performed to identify predictive pathological and immunological biomarkers, including centrally determined ER and progesterone receptor (PR). ER was considered poor if the range was 0–6 and rich if the range was 7–8. Likewise, PR was considered poor if the range was 0–4 and rich if the range was 5–8. 

A total of 6,120 patients were eligible for analysis. 

  • Triple negative tumors
  • HER2+ tumors
  Number of patients Disease-free survival Overall survival Cumulative incidence of relapse
Exemestane 3,075 66.8% 75% 20%
Sequential therapy 3,045 66.8% 73% 22%

In the 10-year TEAM explorative per protocol analysis (n = 4041), Allred scores were available for 2,996 patients and immunologic markers for 1,754 patients. Patients with above-median numbers of exemestane monotherapy showed a more positive effect for RFS on patients with high FoxP3-positive T-cells compared to patients with low numbers of FoxP3-positive cells (p < 0.001 versus p = 0.97, respectively). Exemestane monotherapy was associated with more benefit for patients with a high tumor differentiation grade (p < 0.001) with a borderline significant interaction (p = 0.07). Researchers also found a borderline significant treatment by marker effect interaction, with ER-rich HR (mean = 0.69) showing statistical significance (p < 0.001) but ER-poor HR (mean = 0.94) showing no significance (p = 0.71).

The researchers concluded, “Interestingly, the number of regulatory T-cells was a predictive factor for the benefit of exemestane monotherapy, which implies a role of the local immune system in endocrine therapy. Furthermore, data suggested that patients with a higher differentiation grade or ER-rich tumor derive more benefit from exemestane monotherapy.”