Joyce Slingerland MD FRCP (C) PhD
Braman Family Breast Cancer Institute,
University of Miami, Miami, FL

About two-thirds of breast cancers express the estrogen receptor (ER). These ER positive breast cancers can be treated with anti-estrogen drugs like tamoxifen or aromatase inhibitors. Unfortunately, most breast cancers that are treated with anti-estrogen therapy develop resistance to these drugs. Dr. Slingerland's lab has shown that estrogen promotes breast cancer growth by causing the degradation of a key cell cycle inhibitor, p27. They also showed that estrogen deprivation and drugs that block the ER including tamoxifen and Faslodex depend on p27 to cause breast cancer cells to stop growing. p27 levels are often reduced in human breast cancers and this predicts poor patient outcome and poor response to tamoxifen therapy. The researchers' recent work showed that the oncogene Src acts on p27 to change its shape and function and promotes p27 degradation in breast cancer cells. BCRF support will allow the researchers to investigate further how Src activation alters p27 function, and to also test whether Src activation (seen in many human breast cancers) is associated with p27 loss in primary human breast cancer tumors and if both of these findings together may predict poor patient outcome. They will also test in laboratory models whether Src inhibitor drugs can cooperate with ER blockers to delay or prevent growth of anti-estrogen resistant tumors. These studies may provide key data to support clinical trials of Src inhibitors together with anti-estrogens in women with ER positive breast cancer.