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 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!!