Adrian Lee, PhD

Improving treatment for invasive lobular breast cancer by inhibiting tumor growth.

Impact

Invasive lobular cancer (ILC) accounts for 10-15% of all breast cancers. While an estrogen receptor (ER)-positive breast cancer, the unique biology of ILC distinguishes it from other ER-positive diseases. As a discrete breast cancer subtype, ILC is the sixth most common cancer in women. The major feature of ILC is mutation and subsequent loss of E-cadherin, a cell adhesion protein molecule important to normal breast tissue architecture. Dr. Lee and his team study unique features of ILC.

Progress Thus Far

Previous research from the team suggests there is a link between the loss of E-cadherin and mutations in the gene that codes for the HER2 protein, ERBB2. For example, mutations in ERBB2 are enriched in the ILC breast cancer compared to invasive ductal breast cancer. In the past year, the team has made significant progress developing sophisticated laboratory models that express these HER2 mutations. Using these models, they have gained a better understanding of how the loss of E-cadherin and mutations in HER2 cooperate to promote ILC growth and affect sensitivity to HER2 therapy.

What’s next

The team will use state-of-the-art tests to confirm the prevalence and identity of ERBB2 mutations in patients with ER-positive metastatic breast cancer. They also plan to explore synergy between drugs that target HER2 and new antibody drug conjugates in their engineered models. These studies will help the team further understand the significance of HER2 mutations in ILC, which may impact the management of HER2-mutated ILC in patients.