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A genome-scar score built from three measures of chromosomal damage, with 42 as the cut-off, picked out triple-negative tumours that melted away on platinum chemotherapy before surgery, including tumours without a BRCA mutation.
A combined HRD score, the unweighted sum of loss of heterozygosity, telomeric allelic imbalance and large-scale state transition scores, was assessed in three neoadjuvant TNBC trials of platinum-containing therapy, with HR deficiency defined as HRD score 42 or more or BRCA1/2 mutation. In the platinum, gemcitabine and iniparib trial HR deficiency predicted residual cancer burden 0/I and pathological complete response (OR 4.96 and 6.52), remaining significant after clinical adjustment (OR 5.86); in two cisplatin trials it predicted RCB 0/I and pCR (OR 10.18 and 17.00; multivariable OR 12.08). Among BRCA1/2 non-mutated tumours response was higher with high HRD scores.
This paper set the HRD score threshold the myChoice assay still uses and showed that genomic scars extend platinum sensitivity beyond BRCA carriers in early TNBC, though the TNT trial later found the same score did not predict carboplatin benefit in advanced disease.
Shares HRD & BRCA testing, Residual cancer burden (RCB), Homologous recombination deficiency (HRD), Pathologic complete response (pCR).
Shares HRD-positive (genomic instability score), HRD genomic scar scores (GIS, LOH, HRDetect), HRD & BRCA testing, Homologous recombination deficiency (HRD).
Shares myChoice CDx, HRD-positive (genomic instability score), HRD & BRCA testing, Homologous recombination deficiency (HRD).
Shares myChoice CDx, HRD-positive (genomic instability score), Homologous recombination deficiency (HRD), BRCA1 / BRCA2 (HRD).
Shares HRD-positive (genomic instability score), HRD & BRCA testing, Homologous recombination deficiency (HRD), BRCA1 / BRCA2 (HRD).
Shares Residual cancer burden (RCB), Pathologic complete response (pCR), Early triple-negative breast cancer, Platinum agents.
Shares Residual cancer burden (RCB), Pathologic complete response (pCR), Early triple-negative breast cancer, Platinum agents.
Shares Residual cancer burden (RCB), Early triple-negative breast cancer, Platinum agents, Cisplatin.