Editing Breast cancer (section)

=== Molecular profiling - breast cancers can be broken down into four different groups depending on the 'molecular portrait' ===

** Note that the molecular profile is independent of histological subtype (e.g. ductal vs lobular)

** Oestrogen receptor (ER)
*** '''Luminal A''' (40%)
**** ER+, PR+, HER2-; Ki67 <14%
**** Low-grade and good prognosis
**** 'Luminal' refers to the similar molecular profile to luminal epithelium of normal breast tissue
**** This type has best response rate to endocrine therapy
**** PR positivity predicts response to endocrine therapy regardless of ER positivity
**** Doesn't typically respond well to chemotherapy
*** '''Luminal B''' (20%)
**** ER+, PR+/-, HER2+/-; Ki67 >14%
**** Worse prognosis than luminal A
**** Has a lower response to endocrine therapy than luminal A but higher response to chemotherapy
** '''HER-2 enriched''' (10%)
*** ER-, PR-, HER2+
*** Characterised by high expression of HER2 and proliferation gene clusters and low expression of luminal clusters
*** Some are ER+ but not that common
*** Often node-positive
*** P53 mutations
** '''Basal-like''' (15%)
*** ER-, PR-, HER2-
*** Gene cluster profile similar to basal epithelial cells, characterised by low expression of the luminal and HER2 gene clusters - typically triple negative, but about 20% are not.
*** Not the same as triple-negative, although there is a lot of overlap between the two categories
*** Most aggressive breast cancer, accounts for about 10-20% of cases.
*** More frequently affects younger patients <40 years.
*** Tumours tend to be larger, palpable, higher grade
*** Distant mets often occur at visceral sites and are seen within the first 3 years after diagnosis
*** 20% of triple negative cancers are BRCA1 positive, and 10% of basal-like tumours overall are BRCA1 positive