HPSE and obesity due to melanocortin 4 receptor deficiency: Given this complexity, our findings pointing to the ability of heparanase to dictate the ER−inducing phenotype of Mφ in BC (Figure 5 and Figure 6), and, therefore, control one of the fundamental features of hormone-dependent breast tumorigenesis, namely, the level of ER expression, suggest that modulation of the enzyme activity (rather than targeting Mφ per se [95]) may offer an appealing alternative approach to uncouple obesity and breast cancer progression in a rapidly growing population of obese patients.