Editing Breast cancer (section)

=== Molecular markers ===

** ER background
*** Positive in about 80% of breast cancers
*** Ligand-dependent transcription factor, member of the steroid hormone receptor superfamily. When oestrogen binds, promoter regions of DNA are triggered. Has two subunits - ER-alpha and ER-beta
**** See 'reproductive physiology' under 'O+G' for background on oestrogens
*** Clinical ER assays measure ER-alpha, and quantitate using immunohistochemistry, and level of expression predicts response to endocrine therapy - 70% of ER+/PR+ cancers respond
*** Graded on intensity of scoring (0 to 3+) and proportion of staining (percentage)
**** >1% staining is considered positive
**** 1-10% is low positive
**** Allred Score out of 8 combines intensity and positivity
*****[[File:Allred-score-guidelines-for-ER-and-PR-evaluation.png|none|Allred score for ER and PR evaluation|thumb|441x441px]]
*** 65% of ER+ cancers are also PR+
*** Some ER-/PR+ cancers also respond to endocrine therapy, but this is a rare combination
** HER2
*** Tyrosine kinase receptor which functions as a protooncogene when amplified
**** Based on ERBB2 gene, chromosome 17
**** External to internal signalling, influencing growth and differentiation via PI3K, MAPK, JAK/STAT pathways
**** Doesn't bind to ligands, but is activated when it dimerizes with itself or other EGFR family members
*** Associated with high-grade cancers with axillary involvement, and decreased ER/PR expression. HER2 overexpression is also a poor prognostic factor on its own.
*** Amplified '''(rather than mutated)''' in about 13% of breast cancers
*** Scored on a scale of 0 to 3+
**** 0 or 1+ is considered negative
**** 2+ is equivocal - send for ISH
**** 3+ is positive (>30% of cells)
*** Inhibiting the function of the HER-2 receptor slows the growth of HER-2 positive tumours