# Genomically determined subtypes and clinicopathological features as predictors of the efficacy of preoperative chemotherapy combined with HER2-targeted therapy for early-stage HER2-positive breast cancer

## TL;DR

This study shows that genomic subtypes and HER2 staining intensity can predict the effectiveness of preoperative chemotherapy in early-stage HER2-positive breast cancer.

## Contribution

The study identifies HER2 intrinsic subtype and high HER2 staining intensity as independent predictors of pathological complete response in HER2-positive breast cancer patients.

## Key findings

- HER2 intrinsic subtype was associated with significantly higher pathological complete response rates compared to non-HER2 subtypes.
- High HER2 staining intensity was an independent predictor of achieving pathological complete response.
- MP/BP subtyping showed varied 5-year distant disease-free survival rates across different intrinsic subtypes.

## Abstract

Neoadjuvant chemotherapy (NAC) combined with human epidermal growth factor receptor 2 (HER2)-targeted agents is the mainstay of treatment of HER2-positive (HER2 +) breast cancer (BC). We investigated intrinsic subtypes and clinicopathological features as predictors of outcomes of NAC in HER2 + early-stage BC patients.

Of 186 consecutive patients with early-stage HER2 + BC, as determined by immunohistochemistry (IHC) and fluorescence in situ hybridization, who received NAC plus HER2-targeted agents, 167 with an available biopsy specimen were eligible for inclusion. Intrinsic subtypes were determined by MammaPrint and Blueprint (MP/BP). Whole-slide images of HER2 IHC staining were used to evaluate intensity of HER2 staining.

MP/BP subtype was determined for 124 patients: Luminal-A, 17 patients; Luminal-B, 23 patients; HER2, 76 patients; and Basal, 8 patients. Pathological complete response (pCR) rate was significantly higher in HER2 than in non-HER2 cases (p < 0.001). High-intensity (p = 0.001) and BP-determined HER2 intrinsic subtype (p = 0.024) were identified as independent factors for pCR prediction. Neither Luminal subtype was found in IHC estrogen receptor (ER)-negative patients; however, 54.3% of IHC ER-positive patients had HER2 subtype. Five-year distant disease–free survival by MP/BP subtype was Luminal-A, 92.3%; Luminal-B, 81.6%; HER2, 84.0%; and Basal, 80.0%. Of the 23 patients whose subtypes were compared before and after surgery, 10 had a change in subtype.

High HER2 intensity and HER2 intrinsic subtype could be a means for predicting achievement of pCR. The findings indicate the essential role of MP/BP subtyping in the treatment of HER2 + BC.

UMIN000049957.