RNA sequencing of serial samples from patients enrolled in the NA-PHER2 trial

Improved outcomes in HER2+ breast cancer have resulted from chemotherapy and anti-HER2 therapies. However, HER2+ER+ cancers exhibit lower response rates. The NA-PHER2 trial investigated chemo-free preoperative HER2 and CDK4/6 blockade with or without endocrine therapy in HER2+ER+ breast cancer. Through RNA sequencing and tumour infiltrating lymphocytes (TIL) assessment in serial biopsies we identified predictive biomarkers of pCR, Day 14 Ki67 response, and unveiled treatment-induced molecular changes.

Type: RNASeq
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD50000000363	We performed whole transcriptome RNA sequencing on serial tumour biopsies collected at baseline, Day 14, and after completion of all neoadjuvant therapy from the NA-PHER2 trial. Patients received neoadjuvant treatment with the combined regimen of trastuzumab, pertuzumab, palbociclib with or without addition of fulvestrant. Transcriptomic profiles were generated from 143 samples (Baseline n = 53, Day 14 n = 49, Surgery n = 41) corresponding to 53 of the 58 patients enrolled in NA-PHER2 trial (91.4%). RNA sequencing was performed on total RNA samples derived from formalin-fixed, paraffin-embedded (FFPE) tissue sections. RNA-Seq libraries were produced using NEBNext® Ultra™ II Directional RNA Library Prep Kit. The capture was then performed on cDNA libraries with the Twist Human Core Exome Enrichment System according to supplier recommendations (Twist Bioscience). The obtained eluted-enriched DNA samples was then sequenced on an Illumina NovaSeq as paired-end 100bp reads. FASTQ files are provided.	unspecified	147

Publications	Citations
Determinants of response and molecular dynamics in HER2+ER+ breast cancers from the NA-PHER2 trial receiving HER2-targeted and endocrine therapies. Callari M, Dugo M, Barreca M, Győrffy B, Galbardi B, Vigano L, Locatelli A, Dall'Ara C, Ferrarini M, Bisagni G, Colleoni M, Mansutti M, Zamagni C, Del Mastro L, Zambelli S, Frassoldati A, Biasi O, Pusztai L, Valagussa P, Viale G, Gianni L, Bianchini G. Nat Commun 16: 2025 2195	0

Publications

Citations

Determinants of response and molecular dynamics in HER2+ER+ breast cancers from the NA-PHER2 trial receiving HER2-targeted and endocrine therapies.
Callari M, Dugo M, Barreca M, Győrffy B, Galbardi B, Vigano L, Locatelli A, Dall'Ara C, Ferrarini M, Bisagni G, Colleoni M, Mansutti M, Zamagni C, Del Mastro L, Zambelli S, Frassoldati A, Biasi O, Pusztai L, Valagussa P, Viale G, Gianni L, Bianchini G. Nat Commun 16: 2025 2195