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On-treatment transcriptional profiling in HER2+ inflammatory breast cancer

ABSTRACT: Inflammatory breast cancer (IBC) is a rare and understudied disease, with 40% of cases presenting with HER2-positive IBC. Within a cohort of newly diagnosed patients with HER2-positive IBC, we sought to (i) assess the pathologic complete response (pCR) rate of short-term neoadjuvant dual-HER2-blockade and paclitaxel, (ii) define baseline and on-treatment transcriptional profiles of tumor biopsies that are associated with pCR, and (iii) identify biologic pathways that may explain the effect of neoadjuvant therapy on pathologic tumor response.

ORGANISM(S): Homo sapiens

PROVIDER: GSE207248 | GEO | 2022/09/01

REPOSITORIES: GEO

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Project description:The purpose of this study was to identify molecular markers of pathologic response to neoadjuvant paclitaxel/radiation treatment, protein and gene expression profiling were done on pretreatment biopsies. Patients with high-risk, operable breast cancer were treated with three cycles of paclitaxel followed by concurrent paclitaxel/radiation. Tumor tissue from pretreatment biopsies was obtained from 19 of the 38 patients enrolled in the study. Protein and gene expression profiling were done on serial sections of the biopsies from patients that achieved a pathologic complete response (pCR) and compared to those with residual disease, non-pCR (NR). Proteomic and validation immunohistochemical analyses revealed that Î±-defensins (DEFA) were overexpressed in tumors from patients with a pCR. Gene expression analysis revealed that MAP2, a microtubule-associated protein, had significantly higher levels of expression in patients achieving a pCR. Elevation of MAP2 in breast cancer cell lines led to increased paclitaxel sensitivity. Furthermore, expression of genes that are associated with the basal-like, triple-negative phenotype were enriched in tumors from patients with a pCR. Analysis of a larger panel of tumors from patients receiving presurgical taxane-based treatment showed that DEFA and MAP2 expression as well as histologic features of inflammation were all statistically associated with response to therapy at the time of surgery. We show the utility of molecular profiling of pretreatment biopsies to discover markers of response. Our results suggest the potential use of immune signaling molecules such as DEFA as well as MAP2, a microtubule-associated protein, as tumor markers that associate with response to neoadjuvant taxaneâbased therapy. Tumor tissues from pretreatment needle biopsies from patients enrolled on a paclitaxel/radiation clinical trial were laser capture microdissected for RNA extraction and hybridization to Affymetrix microarrays. We analyzed one array (sample A) from duplicate samples from each patient. 14 subject, 2 replicates each.

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On-treatment transcriptional profiling in HER2+ inflammatory breast cancer

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