Gene Expression Profiles Associated with Molecular Subtypes and Pathological Response to Neoadjuvant Treatment in Surgical Breast Cancer

TL;DR

This study explores gene expression patterns in breast cancer patients before chemotherapy to identify markers linked to treatment response and tumor subtypes.

Contribution

The study identifies novel associations between low AXL and BRCA1 gene expression and pathological complete response to neoadjuvant chemotherapy in breast cancer.

Findings

Hormone receptor-positive tumors showed higher expression of AXL, FGFR1, RAP80, GAS6, BTRCP, and ZNF217.

Low AXL and BRCA1 expression levels were independently associated with pathological complete response (pCR).

Combined low expression of AXL and BRCA1 was most strongly associated with pCR in this cohort.

Abstract

Chemotherapy has significantly improved survival in breast cancer and, in the neoadjuvant setting, contributes to tumor downstaging and increased rates of breast-conserving surgery while enabling in vivo assessment of tumor biology and chemosensitivity. Pathological complete response (pCR) is a key endpoint associated with favorable outcomes; however, tumor heterogeneity highlights the need for reliable predictive biomarkers. This study evaluated the mRNA expression of 13 candidate genes in relation to molecular subtypes and pathological response to neoadjuvant chemotherapy (NAC) to identify potential predictive and prognostic markers. Pretreatment core biopsies from 92 patients receiving NAC were analyzed by quantitative RT-PCR. Molecular subtypes were determined by immunohistochemistry (ER, PR, HER2, Ki67), and pathological response was classified using the Miller–Payne scale as good (MP 4/5) or poor (MP 1–3). Multivariate logistic regression assessed associations between gene expression, subtype, and pCR. Hormone receptor-positive tumors showed significantly higher expression of AXL, FGFR1, RAP80, GAS6, BTRCP, and ZNF217. Significant associations with pCR were observed for AXL, FGFR1, YAP, and BRCA1. Low AXL and BRCA1 expression levels were independently associated with pCR. In addition, their combined low expression was associated most strongly with breast pCR in this cohort. These findings should be interpreted as exploratory and require validation in independent cohorts.

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