INS and breast cancer: That is, hormonal factors influencing the natural history of some human malignancies including breast cancer (e.g. estrogen, insulin, IGF-1) could begin to manifest their effects in unexpected short timescales and the observed effects (i.e. rapid increase of breast cancer risk) are likely to reflect not the initiation of new tumors but rather the growth of subclinical malignant lesions to clinically diagnosable volumes [70].