Lack of benefit of neoadjuvant pertuzumab in high risk HER2 positive breast cancer: A retrospective case-control study of 355 cases with biomarker analysis

Abstract

Background: The NEOSPHERE trial suggested that pertuzumab (P) added to a combination of docetaxel and trastuzumab (T) as a neoadjuvant therapy in HER2 positive breast cancer (HER2+ BC) patients (pts) significantly enhances pathological complete response (pCR) rates. Here, we report our institution experience, focusing on stage III tumors. Methods: We reviewed clinical and pathological response (residual cancer burden, RCB) in 355 HER2+BC treated between 2010 and 2017 with neoadjuvant chemotherapy combined with T (n=291) or TP (n=64). Results were adjusted according to clinical stage, hormone receptors (HR) status, and chemotherapy regimen. In a subset of 157 pts matched on clinical TNMstage and HR expression (T, n=98; TP, n=59), a baseline pathological biomarker analysis was performed to assess TILs, PTEN, FOXP3 and PD-L1 expression. Results: Among 355 patients, tumor clinical stages were T3-T4 for 40% vs. 72% of T and TP pts (p<0.0001). HR were expressed in 40% of T group and 22% of TP group (p=0.002). Most tumors were grade 3 (63% in both groups). Almost all pts received taxanes, and 81% (T) vs. 69% (TP) received anthracyclines (p=0.03). Breast conserving surgery (BCS) was performed in 52% (T) and 34% (TP) of pts (p=0.008). pCR (RCB=0) was observed in 43% and 51% of T and TP groups, respectively (p=0.25). For stage III pts, pCR was achieved in 48% (T) and 53% (TP) of pts (p=0.25). Multivariate analyses did not show any independent factor associated with pCR. Features of the biomarker subset were similar among both groups: stage III=81%; HR negative=70%; grade 3=63%; anthracyclines 79% (T) and 68% (p=0.09); BCS=31%. RCB=0 was seen in 50% (T) and 53% (TP) of pts (p=0.93). Immune cells infiltration (CD8+, PD-L1+ and FOXP3+lymphocytes) and tumor PD-L1 expression rates were higher in TP group (p<0.0001). None of the pathological biomarkers correlated with pathological response. Conclusions: This retrospective study did not suggest any benefit of neoadjuvant TP dual HER2 blockade regarding pathological response for stage III HER2+ BC. Baseline pathological expressions of PTEN, FOXP3, TILs, PD-L1 did not correlate with pathological response.