The addition of 2.5 mg/d medroxyprogesterone acetate to 0.625 mg/d conjugated equine estrogen may have an impact on the IGF pathway proteins and may affect circulating levels of extracellular matrix proteins (for example, MMP2) of potential relevance to the less-favorable E+P effects, compared with those for E-alone, on breast cancer, and CHD. Here, MMP2 is linked to breast cancer.