Neutrophil gelatinase-associated lipocalin (NGAL) predicts response to neoadjuvant chemotherapy and clinical outcome in primary human breast cancer

In our previous work we showed that NGAL, a protein involved in the regulation of proliferation and differentiation, is overexpressed in human breast cancer (BC) and predicts poor prognosis. In neoadjuvant chemotherapy (NACT) pathological complete response (pCR) is a predictor for outcome. The aim of this study was to evaluate NGAL as a predictor of response to NACT and to validate NGAL as a prognostic factor for clinical outcome in patients with primary BC. Immunohistochemistry was performed on tissue microarrays from 652 core biopsies from BC patients, who underwent NACT in the GeparTrio trial. NGAL expression and intensity was evaluated separately. NGAL was detected in 42.2% of the breast carcinomas in the cytoplasm. NGAL expression correlated with negative hormone receptor (HR) status, but not with other baseline parameters. NGAL expression did not correlate with pCR in the full population, however, NGAL expression and staining intensity were significantly associated with higher pCR rates in patients with positive HR status. In addition, strong NGAL expression correlated with higher pCR rates in node negative patients, patients with histological grade 1 or 2 tumors and a tumor size <40 mm. In univariate survival analysis, positive NGAL expression and strong staining intensity correlated with decreased disease-free survival (DFS) in the entire cohort and different subgroups, including HR positive patients. Similar correlations were found for intense staining and decreased overall survival (OS). In multivariate analysis, NGAL expression remained an independent prognostic factor for DFS. The results show that in low-risk subgroups, NGAL was found to be a predictive marker for pCR after NACT. Furthermore, NGAL could be validated as an independent prognostic factor for decreased DFS in primary human BC

PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer.

Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in breast cancer, with mutations in PIK3CA being the most common. This study investigated the association between PIK3CA genotype and pathologic complete response (pCR) rates in human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with either dual or single anti-HER2 treatment in addition to neoadjuvant chemotherapy.info:eu-repo/semantics/publishe

Univariate Cox Survival Analysis for NGAL expression.

<p>Abbreviations: NGAL, Neutrophil gelatinase-associated lipocalin; pCR, pathologic complete response; HER2, human epidermal growth factor receptor 2; E, number of events; N, total sample size.</p

Multivariate Cox Survival Analysis - Disease-free survival.

<p>Multivariate Cox Survival Analysis - Disease-free survival.</p

Multivariate Cox Survival Analysis - Overall survival.

<p>Multivariate Cox Survival Analysis - Overall survival.</p

Long-term outcome of patients depending on NGAL expression and intensity in months.

<p>(<b>A</b>) DFS in all patients by NGAL expression neg. vs. pos. (<b>B</b>) DFS in all patients by NGAL intensity 0–1 vs. 2–3. (<b>C</b>) DFS in HR positive patients by NGAL expression neg. vs. pos. (<b>D</b>) DFS in HR positive patients by NGAL intensity 0–1 vs. 2–3. (<b>E</b>) DFS in patients without pCR by NGAL expression neg. vs. pos. (<b>F</b>) OS in patients without pCR by NGAL intensity 0–1 vs. 2–3. NGAL: neutrophil gelatinase-associated lipocalin. DFS: disease-free survival. OS: overall survival. HR: hormone.</p

NGAL expression in human breast cancer tissues.

<p>(A) Negative NGAL staining (staining intensity score 0). (B) Weak NGAL staining (staining intensity score 1). (C) Moderate NGAL staining (staining intensity 2). (D) Strong NGAL staining (staining intensity 3). Original magnification: 400×.</p

Association between NGAL-expression and clinicopathologic variables.

<p>Abbreviations: NGAL, Neutrophil gelatinase-associated lipocalin; HER2, human epidermal growth factor receptor 2.</p