HER2-positive neuroendocrine breast carcinoma: a case study uncovers CCND1, FGF19, and IGF1R amplifications as new molecular drivers

Primary neuroendocrine carcinoma of the breast (NEBC) is a rare entity among breast malignancies, and is usually associated with a more aggressive clinical course compared to other types of invasive breast cancer. Although some studies have characterized the molecular profile of NEBCs using targeted sequencing, these tumors are often treated similarly to other primary breast carcinomas despite their unique morpho-phenotypic characteristics.

In this study, we present the case of a woman with HER2-positive primary large cell NEBC with homolateral axillary nodal metastases. After neoadjuvant therapy, the patient underwent surgical resection of the breast, showing a partial pathological response. Next-generation sequencing was performed on pre- and post-treatment samples using a 174-genes panel. Both samples exhibited a similar molecular profile, including a somatic mutation in GATA3 and amplifications of CCND1, FGF19, and IGF1R. ERBB2 amplification was identified in the pre-operative biopsy but was lacking in the post-treatment surgical specimen.

This study represents the first report of CCND1, FGF19, and IGF1R gene amplification in a breast neuroendocrine carcinoma. These findings provide new insights into the molecular profile of this entity and may contribute to future studies on precision oncology.