Secretory carcinoma of the breast: a report of six cases with different immunophenotypes and molecular subtypes

AIM: Secretory carcinoma is a rare and well-recognized subtype of breast carcinoma generally associated with a favourable prognosis. Although it was initially described in young patients, it is now known to occur at any age and in both sexes. Histologically, it is characterized by a combination of solid, microcystic and tubular architectural pattern with the presence of intracellular and extracellular secretory material that provides its distinctive histological appearance. This tumour is associated with a balanced chromosomal translocation t(12;15) resulting in the ETV6-NTRK3 gene fusion, a translocation rearrangement with well-established oncogenic potential. Secretory carcinoma has traditionally been considered an unusual example of a triple-negative tumour, yet with a favourable clinical outcome. METHODS AND RESULTS: In this study, we report six cases exhibiting both typical histological and molecular features of secretory carcinoma, but with varying expression of HER2 and hormone receptors. An extensive immunohistochemical and molecular analysis has been performed, including in situ hybridization and gene expression assays. CONCLUSION: These findings support the existence of greater variability in surrogate and intrinsic molecular subtypes within secretory carcinomas, providing potential personalized therapeutic strategies for the treatment of these patients.