The PI3K/Akt/mTOR pathway is frequently activated in breast cancer (BC) and is implicated in resistance to endocrine therapy (ET). Addition of everolimus (EVE), an mTOR inhibitor, to ET improves cancer control compared to ET alone. However, in previous studies, the median progression-free survival (PFS) did not exceed 7 months (mo), responses were inconsistent and there was no efficient predictive biomarker of efficacy. We aimed to define a correlation between clinical, biological or histological features and EVE efficacy.
Retrospective analysis of metastatic breast cancer (mBC) patients treated with EVE in our centers between 2013 and 2018. Clinical characteristics (type of metastases), biological features (albumin levels, lactate dehydrogenase (LDH) and neutrophil/lymphocyte ratio (NLR)) and tumors features (estrogen or progesterone receptors, KI67, grade) were analyzed. In available tissue samples collected before EVE initiation, immunohistochemistry (IHC) for PTEN, cMET and pS6RP was performed. All these features were correlated with PFS.
There were 61 women, median age 59 yo, with mBC treated with EVE, and 35 tumor samples were available. Median PFS was 6,5 mo (1-32 mo). 3 tumor-related features were associated with poor prognosis (LDH >230 U/L, high NLR (>3) and visceral metastases). A score was made out of these 3 criteria : patients with a “high score” (HS) (2 or 3 criteria) had a low PFS compared to “low score” (LS) patients (0-1 criteria) (4 vs 11 mo, respectively; p < 0,001). Patients with IHC c-MET+ had a lower PFS in LS (4 vs 13,5 mo, p = 0,01) and HS patients (c-MET- PFS 8,5 mo vs 3 mo if c-MET+, p = 0,02). For HS patients with PTEN loss also had a shorter PFS (3 vs 5 mo, p = 0,003). Combining these criteria, PFS in LS PTEN-/cMET- was 10,5 mo and only 3 mo in HS PTEN+/cMET + (p < 0,001).
Visceral metastases, high NLR and high LDH were associated with lower PFS on EVE. They are useful, quick and economic scores to predict EVE efficacy in mBC patients. Additional histological characteristics such as PTEN and c-MET could help determine, within this population of patients, the ones who will and the ones who will not benefit from EVE treatment.
Emmanuel Seront - Hôpital de Jolimont.
Has not received any funding.
All authors have declared no conflicts of interest.