Notably, HMGCS2 expression is retained by all the IACs from our morphologically-defined cohort. This stresses the potential value of HMGCS2 as a breast apocrine cancer biomarker, since other apocrine differentiation markers such as 15-PGDH, ACSM1 and HMGCR reported by us previously, are expressed consistently in Prednisolone benign apocrine lesions but are conserved at lower frequencies or even negative in the invasive stages. Recently, Wang and co-authors using Illumina expression array/RT PCR analysis sought to identify risk biomarkers that are specific to ER status of breast cancer and among several others revealed a significant overexpression of HMGCS2 in ER- cases. However, our data did not confirm overexpression of HMGCS2 in ER negative tumors at the protein level: the group of TNBCs displayed only,2% positives for HMGCS2. IAC as defined by morphological criteria is often characterized by a specific hormone receptor signature: AR+/ER-/PR that has been proposed as a marker for apocrine�Ctype tumors by Tsutsumi and coauthors, who suggested to include androgen receptor to immunohistochemical criteria. The identification of differentially expressed proteins that characterize the progression from early benign apocrine lesions to invasive stages opens a window of opportunity for designing and testing new approaches for pharmacological intervention as, for example, 15-hydroxyprostaglandin dehydrogenase and 3-hydroxymethylglutaryl-CoA reductase are currently being targeted for chemoprevention strategies in various malignancies. HMGCS2 is one of the rate-limiting enzymes controlling generation and re-utilization of Glipizide ketone bodies. Recently it was shown that ketone bodies support the driving of neoplastic growth which is often accompanied by starvation of all components of tumor environment and it has been speculated that ketone inhibitors can be designed as novel therapeutics to effectively treat advanced cancer patients. Consequently, HMGCS2, the enzymes associated with ketone body production and re-utilization, might be considered as new ����druggable���� targets for anticancer therapy.