Influence of semi-quantitative oestrogen receptor expression on adjuvant endocrine therapy efficacy in ductal and lobular breast cancer-A TEAM study analysis

Background: Multiple studies suggest better efficacy of chemotherapy in invasive ductal breast carcinomas (IDC) than invasive lobular breast carcinomas (ILC). However, data on efficacy of adjuvant endocrine therapy regimens and histological subtypes are sparse. This study assessed endocrine therapy efficacy in IDC and ILC. The influence of semi-quantitative oestrogen receptor (ER) expression by Allred score was also investigated. Methods: Dutch and Belgian patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were randomized to exemestane (25 mg daily) alone or following tamoxifen (20 mg daily) for 5 years. Inclusion was restricted to IDC and ILC patients. Histological subtype was assessed locally; ER expression was centrally reviewed according to Allred score (ER-poor (<7; n = 235); ER-rich (≥7; n = 1789)). Primary end-point was relapse-free survival (RFS), which was the time from randomization to disease relapse. Findings: Overall, 2140 (82%) IDC and 463 (18%) ILC patients were included. RFS was similar for both endocrine treatment regimens in IDC (hazard ratio (HR) for exemestane was 0.83 (95% confidence interval (CI) 0.67-1.03)), and ILC (HR 0.69 (95% CI 0.45-1.06)). Irrespective of histological subtype, patients with ER-rich Allred scores allocated to exemestane alone had an improved RFS (multivariable HR 0.71 (95% CI 0.56-0.89)). In contrast, patients with ER-poor Allred scores allocated to exemestane had a worse RFS (multivariable HR 2.33 (95% CI 1.32-4.11)). Significant effect modification by ER-Allred score was confirmed (multivariable p = 0.003). Interpretation: Efficacy of endocrine therapy regimens was similar for IDC and ILC. However, ER-rich patients showed superior efficacy to upfront exemestane, while ER-poor patients had better outcomes with sequential therapy, irrespective of histological subtype, emphasising the relevance of quantification of ER expression. Funding: The Dutch/Belgian TEAM trial is supported by an unrestricted research grant from Pfizer. The sponsors have in no way influenced the design and conduct of the study, collection, management, analysis and interpretation of the data and preparation, review or approval of the manuscript.

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