A woman was diagnosed with mammary adenocarcinoma in the right breast in 1985 at the age of 37, followed by quadrantectomy, lymphadenectomy and irradiation. In 1999, an adenocarcinoma was diagnosed in the left breast, followed by ample resection and anti-oestrogen receptor treatment for 6 years. In April 2014, an infiltrating adenocarcinoma was diagnosed in the right breast that had been operated in 1985. Pre-operative biopsy showed weak positivity for progesterone receptor (PgR, 10%, score 2+). With the goal of boosting her immune system during the 3 weeks preceding surgery, glycosylated oleic acid/vitamin D-binding protein (OAGcMAF) was administered by subcutaneous injections, nebulisation and with a fermented milk product rich in OAGcMAF. No drug was administered in the 3 weeks preceding surgery, nor had the patient received any treatment for the previous 8 years. Following right mastectomy, analysis of the surgical specimen showed no positivity for HER2 expression (negative, score 0) and significant increase in positivity of PgR, from 10% of positivity and a score of 2+ (Figure 1). After 3 weeks of OAGcMAF treatment and subsequent mastectomy, analysis of the surgical specimen showed no positivity for HER2 expression (negative, score 0; Figure 1), thus indicating complete suppression of oncogene expression. Study of the expression of progesterone receptor (PgR, clone 1E2) was consistent with such a reversal of the neoplastic phenotype. PgR expression in the biopsy was low (<1%), a finding consistent with poor differentiation and aggressiveness. However, in the surgical specimen taken after the 3 weeks of treatment with OAGcMAF, PgR expression was significantly increased to 20% (Figure). The selectivity of these effects was confirmed by a study of the expression of Ki67 and estrogen receptor (30% and 90%, respectively) that did not show any change following OA-GcMAF treatment (Figure). Discussion: These results demonstrate that OA-GcMAF, administered by subcutaneous injections, aerosol or in a functional food product, suppressed the expression of HER2, an oncogene which plays a key role in the aetiology, invasive progression and metastasis in breast cancer. This effect was paralleled by increase of PgR expression, thus indicating that OA-GcMAF treatment induced healthy differentiation of cancer cells. We hypothesize that these multifaceted effects on the regulation of gene expression in human breast cancer are due to the peculiar association of OA with GcMAF that is an association between two molecules endowed with anticancer properties. In fact, OA has been shown to down-regulate HER2 expression in cancer cell lines (9) and we demonstrated that GcMAF inhibits human breast cancer cell proliferation and reverts their malignant phenotype (10). We hypothesize that OA-GcMAF, but not OA or GcMAF taken singularly, interacts with the HER2 protein through hydrophobic interaction between the amino-terminal of GcMAF and the extracellular region of HER2, and between the OA-binding region of GcMAF and the plasma membrane (4). In fact, in the stretch of aminoacids between position 17-46 of GcMAF, and position 243-273 of HER2, there is a high density of hydrophobic aminoacids that may favour selective binding. Whatever the case, these results indicate that the effects of OAGcMAF in cancer are due to a multiplicity of actions that involve suppression of oncogene expression
