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The Cancer Genome Atlas profiled hundreds of breast cancers on six platforms and found four main classes; the basal-like class, which is 80% triple-negative, carries TP53 mutation in 80%, frequent PTEN and RB1 loss, MYC and EGFR gains and looks molecularly like high-grade serous ovarian cancer.
Primary breast cancers were analysed by copy-number arrays, DNA methylation, exome sequencing (510 with matched normals), mRNA arrays, microRNA sequencing and reverse-phase protein arrays. Only TP53, PIK3CA and GATA3 were mutated in more than 10% of all breast cancers. Basal-like tumours carried TP53 mutations in 80%, PIK3CA in 9%, PTEN mutation or loss in 35%, INPP4B loss in 30% and RB1 mutation or loss in 20%; PIK3CA (49%), KRAS (32%), BRAF (30%) and EGFR (23%) were amplified or gained but rarely mutated. Comparison with high-grade serous ovarian cancer showed many commonalities, indicating related aetiology and similar therapeutic opportunities. 80% of basal-like tumours were triple-negative.
Deposited as brca_tcga_pub on cBioPortal, with the 2018 PanCancer Atlas re-analysis as brca_tcga_pan_can_atlas_2018.
This is the reference frequency table for basal-like disease: it explains why PARP inhibitors and platinum, borrowed from ovarian cancer, work in TNBC, and why the PI3K pathway is broken by copy number rather than the hotspot mutations that drugs were designed against.
Shares PTEN, PAM50 / intrinsic subtypes, RB1, MYC.
Shares Charles M. Perou, RB1, p53 / RB / cell-cycle checkpoint, Breast cancer (all types).
Shares PTEN, Nature, PIK3CA / PI3K-alpha, TP53.
Shares PAM50 / intrinsic subtypes, PIK3CA / PI3K-alpha, TP53, Breast cancer (all types).
Shares PTEN alteration (sequencing) and PTEN loss (IHC), PTEN, PIK3CA / PI3K-alpha, PI3K / AKT / mTOR.
Shares Charles M. Perou, PAM50 / intrinsic subtypes, Nature, Triple-negative breast cancer (TNBC).
Shares PTEN alteration (sequencing) and PTEN loss (IHC), PTEN, PI3K / AKT / mTOR, Triple-negative breast cancer (TNBC).
Shares Charles M. Perou, PAM50 / intrinsic subtypes, Triple-negative breast cancer (TNBC).