Multiomic analysis of HER2-enriched and AR-positive breast carcinoma with apocrine differentiation and an oligometastatic course: a case report

Front Oncol. 2023 Jul 31:13:1240865. doi: 10.3389/fonc.2023.1240865. eCollection 2023.

Abstract

Breast carcinoma is the most prevalent cancer among women globally. It has variable clinical courses depending on the stage and clinical-biological features. This case report describes a 56-year-old female with invasive breast cancer without estrogen or progesterone receptor expression, with apocrine differentiation, and with no germline variants in the BRCA1 and BRCA2 genes. Throughout the clinical course, the patient exhibited discordant results for HER2 in immunohistochemistry and in situ hybridization. During the second relapse, the disease displayed apocrine microscopic features. The tumor underwent analysis for the androgen receptor, GCDFP-15, RNA-seq, and whole-genome sequencing (WGS) to identify the breast cancer subtype and to characterize the cancer genome. Our bioinformatic analysis revealed 20,323 somatic SNV/Indels, including five mutations in cancer-related genes that are believed to be responsible for the tumor's development. Two of these mutations were found in the PIK3CA and TP53 genes. Furthermore, the tumor tissue exhibited large copy number alterations to the chromosomes, which could impact gene expression through complex mechanisms and contribute to the tumor phenotype. Clustering algorithms applied on RNA-sequencing data categorized this cancer as a HER2+ subtype. The second-line capecitabine chemotherapy treatment is ongoing, and the patient is responding well. Bioinformatic results support the current treatment decision and open the way to further treatments.

Keywords: NGS; WGS; apocrine carcinoma; bioinformatic analysis; breast cancer; case report; nanopore; personalized medicine.

Publication types

  • Case Reports

Grants and funding

The research center CMP3VdA and the Project 5000genomi@VdA are co-founded by “Fondo Europeo di Sviluppo Regionale (FESR) Programma Investimenti per la crescita e l’occupazione 2014/20” (European Social Fund, ESF, and European Regional Development Fund, ERDF), the Autonomous Region of the Aosta Valley, and the Italian Ministry of Labour and Social Policy (CUPB68H19005520007). BP, MM, FF, VP, DC have carried out this work supported by a grant of the EU-ESF, the Autonomous Region of the Aosta Valley, and the Italian Ministry of Labour and Social Policy.