The 21-gene RS was strongly associated with a higher risk of breast cancer recurrence (28% higher risk per 10-unit increase in the RS), and such prognostic impact was more pronounced among women with relatively favorable metabolic profiles in relevant to an absence of obesity, insulin resistance, hyperglycemia, hypertension, or dyslipidemia (28–44% higher risk per 10-unit increase in the RS) and among women with a low level of insulin, C-peptide, or the IGF1/IGFBP3 ratio (41–155% higher risk per 10-unit increase in the RS). The gene discussed is IGFBP3; the disease is obesity due to melanocortin 4 receptor deficiency.