Breast and ovarian cancers are responsible for more than 500,000 female deaths worldwide each year. Fifteen percent of the 230,000 women in the USA diagnosed with breast cancer in 2013 will have triple-negative breast cancer, a disease with few options for treatment, and a twofold greater mortality risk than other breast cancers. The OGF-OGF receptor pathway is present in these cancers, and regulates cell proliferation during homeostasis and disease. OGF is a tonically active peptide that inhibits DNA synthesis by upregulation of cyclin-dependent inhibitory kinases, without disrupting cell migration, differentiation or apoptosis. OGF receptor is a determinant in the proliferation of triple-negative breast cancer and ovarian cancer, and can be genetically modified to alter neoplastic cell replication in vitro and in nude mice. Preclinical studies warrant the use of OGF alone, or in combination, for treatment of triple-negative breast and ovarian cancer patients.