Apocrine carcinoma of the breast: distinctive metabolic reprogramming and high‐frequency PIK3CA mutations revealed by molecular and immunohistochemical analysis

Aims Apocrine carcinoma ( AC ) is a rare and distinct subtype of invasive breast carcinoma, typically characterized by androgen receptor ( AR ) positivity and negative expression of oestrogen and progesterone receptors. This study aimed to clarify the metabolic and molecular characteristics of AC , with a particular focus on protein expression related to lipid metabolism and the frequency and nature of PIK3CA mutations. Methods We analysed tissue specimens from 40 cases with AC and 59 cases with other breast cancer subtypes ( ER +/ HER2 −, ER +/ HER2 +, ER −/ HER2 + and triple‐negative breast cancer [ TNBC ]). Immunohistochemistry was performed for a panel of lipid metabolism‐related proteins including FASN , AMACR , ACOX1 , ACSL1 and catalase. mRNA Expression of ACSL1 was assessed by RT ‐ qPCR and PIK3CA mutations were analysed via targeted sequencing. Results AC showed significantly higher expression of enzymes involved in fatty acid synthesis and peroxisomal β‐oxidation compared to other subtypes. Notably, ACSL1 was upregulated at both protein and mRNA levels, and catalase was upregulated at the protein level, indicating an increase in peroxisomes. PIK3CA Mutations, particularly the hotspot p. H1047R variant, were detected at a significantly higher frequency in AC (68.4%) compared to the other subtypes: ER +/ HER2 − (52.6%), ER +/ HER2 + (27.3%), ER −/ HER2 + (50.0%) and TNBC (33.3%) ( P < 0.05). Conclusions AC is characterized by distinct metabolic reprogramming, with preferential upregulation of peroxisomal β‐oxidation rather than mitochondrial pathways. These metabolic features are accompanied by a high prevalence of activating PIK3CA mutations, suggesting a link between genomic alterations and metabolic phenotype. These findings provide new insights into the pathobiology of AC and may assist in its histopathological differentiation from other breast cancer subtypes.