Breast cancers that have an overactive PI3K enzyme, involved in cell growth and division, tend to be more aggressive and to spread and divide more like stem cells. But a new study by Ralitsa Madsen of University College London and colleagues publishing November 11 in the journal PLOS Genetics uncovers a surprising relationship between PI3K activity and mutations in the PIK3CA gene that codes for the enzyme. Breast cancer tumors with one mutant copy of the PIK3CA gene tend to have lower PI3K activity. In comparison, patients with two or more copies often had higher PI3Kα activity, resulting in more aggressive tumors and a poorer prognosis for patients with certain types of breast cancer.