INS and obesity due to melanocortin 4 receptor deficiency: The above clinical observations (although limited by a small sample size), along with importance of insulin-INSR signaling in diabetes/obesity-related cancer [2, 3, 6–8] and the recent report on heparanase-augmented INSR signaling in myeloma [15], lead us to hypothesize that heparanase facilitates breast carcinoma progression under diabetic conditions via augmentation of INSR signaling.