Abstract
PurposeAccording to the 2017 St Gallen surrogate definitions of the intrinsic subtypes, Ki67, progesterone receptor (PR) and Nottingham histological grade (NHG) are used for prognostic classification of estrogen receptor (ER) positive/HER2-negative breast cancer into luminal A- or luminal B-like. The aim of the present study was to investigate if additional biomarkers, related to endocrine signaling pathways, e.g., amplified in breast cancer 1 (AIB1), androgen receptor (AR), and G protein-coupled estrogen receptor (GPER), can provide complementary prognostic information in a subset of ER-positive/HER-negative invasive lobular carcinoma (ILC).MethodsBiomarkers from 224 patients were analyzed immunohistochemically on tissue microarray. The primary endpoint was breast cancer mortality (BCM), analyzed with 10- and 25-year follow-up (FU). In addition, the prognostic value of gene expression data for these biomarkers was analyzed in three publicly available ILC datasets.ResultsAIB1 (high vs. low) was associated to BCM in multivariable analysis (adjusted for age, tumor size, nodal status, NHG, Ki67, luminal-like classification, and adjuvant systemic therapy) with 10-year FU (HR 6.8, 95% CI 2.3–20, P = 0.001) and 25-year FU (HR 3.0, 95% CI 1.1–7.8, P = 0.03). The evidence of a prognostic effect of AIB1 could be confirmed by linking gene expression data to outcome in independent publicly available ILC datasets. AR and GPER were neither associated to BCM with 10-year nor with 25-year FU (P > 0.33). Furthermore, Ki67 and NHG were prognostic for BCM at both 10-year and 25-year FU, whereas PR was not.ConclusionsAIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative ILC.
Highlights
Estrogen receptor (ER) positive/HER2-negative breast cancer (BC) comprises 75–80% of all BC and this fraction is even higher (> 90%) in invasive lobular carcinoma (ILC) [1, 2]
With only four PM G protein-coupled estrogen receptor (GPER)-positive tumors, it was not meaningful to analyze this biomarker in relation to breast cancer mortality (BCM) (Table 2)
GPER was not associated with survival in any of the datasets (Online Resource 3). In this well-characterized case series of patients with ER-positive/HER2-negative ILC, a small subgroup of 14 patients (7%) was found to have high expression of the estrogen receptor coactivator Amplified in breast cancer 1 (AIB1), and five of them died from breast cancer within approximately 5 years, translating to a high cumulative 5-year mortality in this subgroup compared to that in the large subgroup of patients with lower, or no, expression of AIB1 (Fig. 2)
Summary
Estrogen receptor (ER) positive/HER2-negative breast cancer (BC) comprises 75–80% of all BC and this fraction is even higher (> 90%) in invasive lobular carcinoma (ILC) [1, 2]. The luminal-like (HER2-negative) classification together with tumor size, axillary lymph node status (nodal status), and age is widely used in the clinic for prognostication and treatment decisions (endocrine therapy ± chemotherapy). These established prognostic variables still have their limitations, and there is an unmet need for additional prognostic biomarkers
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