INS and obesity due to melanocortin 4 receptor deficiency: In the context of breast cancer, both obesity and post-diagnostic weight gain have been shown to significantly increase the risk of mortality [15,64], and intentional weight loss in the general population has been shown to favourably affect numerous breast cancer-relevant risk factors and potential mediators, such as circulating oestrogens, sex-hormone binding globulin, inflammatory markers and insulin sensitivity [65], so one might expect to see a positive effect of intentional weight loss on survival.