Abstract
Background: We evaluated immunohistochemical AR expression and correlation with prognosis in a large series of homogeneously treated patients with primary TNBC.Material and Methods: Patients diagnosed with stage I-III TNBC between 2000 and 2015 at Istituto Oncologico Veneto who received treatment with surgery and neoadjuvant and/or adjuvant chemotherapy were included. Whole tissue slides were stained for AR. AR-positive expression was defined as >1% of positively stained tumor cells. Distant-disease-free survival (DDFS) was calculated from diagnosis to distant relapse or death. Late-DDFS was calculated from the landmark of 3 years after diagnosis until distant relapse or death.Results: We included 263 primary TNBC patients. Mean AR expression was 14% (range 0–100%), and 29.7% (n = 78) of patients were AR+. AR+ vs. AR- cases presented more frequently older age (p < 0.001), non-ductal histology (p < 0.001), G1-G2 (p = 0.003), lower Ki67 (p < 0.001) and lower TILs (p = 0.008). At a median follow up of 81 months, 23.6% of patients experienced a DDFS event: 33.3% of AR+ and 19.5% of AR- patients (p = 0.015). 5 years DDFS rates were 67.2% and 80.6% for AR+ and AR- patients (HR = 1.82 95%CI 1.10–3.02, p = 0.020). AR maintained an independent prognostic role beyond stage, but when TILs were added to the model only stage and TILs were independent prognostic factors. AR was the only factor significantly associated with late-DDFS: 16.4% of AR+ and 3.4% of AR- patients experienced a DDFS after the landmark of 3 years after diagnosis (p = 0.001). Late-DDFS rates at 5 years from the 3-year landmark were 75.8% for AR+ and 95.2% for AR- patients (log-rank p < 0.001; HR = 5.67, 95%CI 1.90–16.94, p = 0.002).Conclusions: AR expression is associated with worse outcome for patients with TNBC. In particular, AR+ TNBC patients are at increased risk of late DDFS events. These results reinforce the rationale of AR targeting in AR+ TNBC.
Highlights
Triple negative breast cancer (TNBC) represents the most lethal breast cancer subtype, accounting for around 15% of all breast cancer diagnoses and being associated with an increased risk of relapse at distant sites, mostly occurring within the first 3 years from diagnosis [1]
AR expression was evaluated on the following FFPE primary tumor samples for main analyses: surgical sample for patients treated with primary surgery followed by adjuvant chemotherapy and diagnostic core-biopsy for patients treated with neoadjuvant chemotherapy followed by surgery
In case of patients treated with neoadjuvant chemotherapy showing residual invasive breast cancer at the examination of the surgical sample, the FFPE surgical tumor block was retrieved in order to conduct exploratory analysis of changes in AR expression from pre- to post-neoadjuvant chemotherapy
Summary
Triple negative breast cancer (TNBC) represents the most lethal breast cancer subtype, accounting for around 15% of all breast cancer diagnoses and being associated with an increased risk of relapse at distant sites, mostly occurring within the first 3 years from diagnosis [1]. It is defined by the absence of expression of estrogen and progesterone receptors and lack of HER-2 overexpression/amplification. At least four main TNBC subtypes have been defined [3, 4], including the luminal androgen receptor (LAR) class, which is enriched for hormonally regulated pathways and is dependent on AR signaling.
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