EvidenceEarly triple-negative breast cancer

Three-quarters of chemotherapy-naive TNBC would be low or ultralow by the DESTINY-Breast06 definitions, but ultralow is unlabelled in TNBC and carries no prognostic weight.

The evidence behind the stage I de-escalation statement on the triple-negative page: an ordinary haematoxylin and eosin slide identifies a fifth of patients whose outcome without chemotherapy matches treated cohorts. A prospective trial of chemotherapy omission is the missing step.

This is the population-based prevalence for the two label thresholds in early TNBC, and it shows the KEYNOTE-355 CPS 10 gate would admit only about a quarter of unselected patients.

ctDNA and RCB measure different things and both should stratify post-neoadjuvant TNBC trials; an RCB-II patient with negative ctDNA has an 87% three-year event-free survival.

The first prospective test of acting on ctDNA in triple-negative disease, and a negative one: with a quarterly, single-mutation assay the window between detectable DNA and visible metastasis was too short to intervene. Later designs use tumour-informed assays, earlier sampling and drugs with more single-agent activity.

ctDNA clearance may refine pCR as a surrogate: a patient with residual disease but no ctDNA may not need escalation, the hypothesis behind ctDNA-guided post-neoadjuvant trials.

The trial-grade HER2-low share for TNBC is about a third, and the survival difference hints that HER2-zero triple-negative disease is the more aggressive group.

Everyone with HER2-negative early breast cancer that meets high-risk criteria should be offered germline BRCA testing, because a positive result now changes treatment: a year of olaparib after chemotherapy reduces relapse and death. It does not apply to low-risk tumours, HER2-positive disease, or somatic-only BRCA mutations.

The proof that a blood test can split residual-disease patients into those likely to relapse and those likely cured, the premise of the ctDNA-guided adjuvant idea; no completed trial has yet acted on the result.

Multi-variant tracking beats a TP53-only assay in TNBC and supports response-adapted designs that read ctDNA mid-chemotherapy.

TILs are prognostic without chemotherapy, which is what a de-escalation biomarker has to show before trials omit treatment on its basis.

TILs are the strongest cheap prognostic biomarker in early TNBC, scored on a standard slide, and the basis of the de-escalation trials that omit chemotherapy in small, lymphocyte-rich tumours.

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.

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.

It fixes the lymphocyte-predominant share of TNBC at about 30% and shows TILs predict chemotherapy response before immunotherapy enters the picture.

One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.

Germline status changes the reading of the platinum question: in early TNBC the carboplatin benefit was seen in non-carriers, so a BRCA result argues for testing everyone rather than reserving platinum for carriers.

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.

The first evidence that molecular subtype predicts chemotherapy response in triple-negative disease, and the origin of the observation that the immune signal in these tumours is real and measurable, which tumour-infiltrating lymphocyte scoring later turned into a prognostic tool.