Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations

It is the evidence that PALB2 and somatic BRCA2 belong in the PARP inhibitor conversation even though the olaparib label stops at germline BRCA.

It established plasma profiling as a routine alternative to tissue for the BRCA question in advanced prostate cancer, with a sensible rule attached: if plasma finds nothing actionable, go back to tissue. It also documents at scale both the extra resistance information plasma gives and the clonal haematopoiesis noise that comes with it.

It defines who a homologous recombination result should send to platinum: core-gene and biallelic carriers, germline or somatic, rather than any repair-gene variant.

The trial behind the second PARP inhibitor licensed in prostate cancer, and the evidence that a somatic BRCA alteration predicts response as well as an inherited one. Together with TOPARP-A it is why tumour as well as germline sequencing is recommended in metastatic disease.

A germline result is not the whole story: without loss of the second allele the tumour may not be repair-deficient, which is why tumour sequencing and, in trials, HRD signatures are read alongside.

It is the best population-based estimate of how much TNBC is homologous recombination deficient, shows that most of it is not germline BRCA, and argues that whole-genome sequencing at diagnosis could stratify trials and pick out the low group that needs something other than DNA-damaging chemotherapy.

Re-biopsy and re-sequencing at relapse can find repair defects and a higher mutation burden that the primary did not show, which matters for PARP inhibitor and immunotherapy eligibility in metastatic TNBC.

The survival evidence behind platinum in early triple-negative disease, and the first large demonstration that most triple-negative tumours are DNA-repair deficient whether or not BRCA is mutated, which is why HRD scores have not become a platinum selection test.