This observation is also consistent with an important role of PAPP-A in breast cancer, since breasts with low endogenous level of IGFBP-5 are likely to be more sensitive to the oncogenic action of PAPP-A since the high PAPP-A/IGFBP-5 ratio would favor a more effective elimination of IGFBP-5. The gene discussed is IGFBP5; the disease is breast cancer.