Breast Cancer Biology Jo Anne Zujewski MD Cancer

Breast Cancer Biology Jo Anne Zujewski, MD Cancer Therapy Evaluation Program Division of Cancer Diagnosis and Treatment National Cancer Institute May 2011

Breast Cancer Theory: Halsted • Operative breast cancer is a local-regional disease • The positive lymph node is the source of distant metastases

Breast Cancer Theory: Systemic • Operative breast cancer is a systemic disease • Positive lymph node is an indicator of host-tumor relationship that permits metastases

Breast Cancer Theory: Spectrum • Operative breast cancer is a systemic disease in many but not all cases • Positive lymph node is correlated with the subsequent appearance of distant metastases

Seminal observations that have led to the current understanding of breast cancer as a family of related diseases, not a single monolithic process. ”

Molecular Portrait of Breast Cancers Basal-like HER-2 “Normal” Sorlie T et al, PNAS 2001 Luminal B Luminal A Slide courtesy of L. Carey

Subtypes and Prognosis Sorlie T et al, PNAS 2001

Genetic Factors § Oncogenes § Cell death genes § Tumor suppressor genes § Cell signaling genes § DNA repair genes § Carcinogen activating/deactivating genes § Cell cycle checkpoint genes § Cellular senescence genes § Cellular differentiation genes § Metastasis/invasion genes

Epigenetic Factors § Hormones § Growth factors § Small interfering RNAs § Post-translational modifications § methylation § protein ubiquination § phosphorylation

Breast Cancer § a multi-step process § genetic changes § epigenetic changes § mutagenic/nonmutagenic risk factors § gene signatures

SIGNAL TRANSDUCTION Cells respond to external signals through pathways. In pathways, messages are sent from the outside of the cell to the inside of the cell through messengers.

Breast Cancer Development, Growth, Survival and Metastasis Involves Multiple Interrelated Pathways Concurrent targeting of multiple pathways will likely be optimal!!