# HER2/CEP17 ratio is associated with pCR after HER2-directed neoadjuvant treatment in the phase III NeoALTTO trial

## TL;DR

This study shows that higher HER2/CEP17 ratios predict better tumor response to HER2-targeted therapy in early breast cancer patients.

## Contribution

The study demonstrates that quantitative HER2/CEP17 ratios predict pCR but not survival in HER2+ breast cancer patients.

## Key findings

- Higher HER2/CEP17 ratios significantly predict pathological complete response (pCR) in multivariate analysis.
- HER2/CEP17 ratios are not associated with event-free survival (EFS).
- Including HER2/CEP17 ratio in a pCR prediction model improves its accuracy.

## Abstract

In early breast cancer, HER2-directed therapies are approved for the treatment of patients with HER2-positive invasive breast cancer as defined by HER2 protein overexpression, or HER2 gene amplification with HER2/CEP17 ratios ≥2.2. Beyond this cut-off, however, it is unknown whether the efficacy of HER2-directed therapy improves with increasing HER2/CEP17 ratios. We evaluated whether quantitative assessment of the HER2/CEP17 ratio predicts pathological complete response (pCR) and event-free survival (EFS) in patients treated with neoadjuvant HER2-based regimen in the prospective phase III NeoALTTO trial.

455 women with HER2-positive early breast cancer, who had received neoadjuvant trastuzumab and/or lapatinib, together with 12 cycles of weekly paclitaxel, were included in this analysis. The HER2/CEP17 ratio in the primary tumor samples was correlated with pCR and survival outcome.

The median HER2/CEP17 ratio was 5.1 (range: 1.1–100.0), and ratios were not associated with age, hormone receptor (HR) status, or any other clinicopathological variable analyzed. The log HER2/CEP17 ratio significantly predicted pCR in both univariate (OR: 1.83; 95 % CI: 1.11–3.01, p = 0.0176) and multivariate analysis (OR: 1.79; 95 % CI: 1.07–2.99, p = 0.0257). Higher HER2/CEP17 ratios were, however, not associated with improved EFS (adjusted HR = 0.795; p = 0.3537). A pCR prediction model including HER2/CEP17 ratio, treatment arm, and HR status improved the predictive strength of treatment arm alone from a ROC AUC value of 0.60–0.69.

In patients treated with HER2-based neoadjuvant therapy, quantitative analysis of the readily available pretreatment HER2/CEP17 ratio by FISH is predictive of pCR.

•Efficacy of anti-HER2 therapy related to HER2 overexpression in HER2+ eBC is unknown.•We evaluated HER2/CEP17 ratio, pCR, and EFS correlation in the NeoALTTO trial.•We found that pre-treatment HER2/CEP17 ratio by FISH predicts pCR but not of EFS.•HER2/CEP17 ratio is a readily available and simple predictor of pCR in HER2+ eBC.

Efficacy of anti-HER2 therapy related to HER2 overexpression in HER2+ eBC is unknown.

We evaluated HER2/CEP17 ratio, pCR, and EFS correlation in the NeoALTTO trial.

We found that pre-treatment HER2/CEP17 ratio by FISH predicts pCR but not of EFS.

HER2/CEP17 ratio is a readily available and simple predictor of pCR in HER2+ eBC.