tnbc-evidence

Three antibody-drug conjugates now used in triple-negative breast cancer carry the same kind of chemotherapy warhead, a topoisomerase inhibitor. Nobody has randomised which to give first or whether the second works after the first; small series suggest it often does not. With two now approved first line, the question decides what a patient gets for the rest of her life.

Every triple-negative patient under 60 in the UK should be offered a BRCA test at diagnosis because the result now changes treatment, and many should be offered a trial, but no one publishes how many are. A national audit through existing cancer registration and genomic laboratory data would show the gap by region before anyone tries to close it.

The Japanese and Korean trial of 910 women whose tumours had survived pre-surgery chemotherapy, in which six months of capecitabine tablets cut deaths by 41 percent, and by 48 percent in the triple-negative group; the first treatment ever shown to help after residual disease.

The 2010 rule that fixed the line between hormone receptor-positive and negative breast cancer at 1 percent of stained tumour nuclei, after finding that up to a fifth of receptor tests worldwide might be wrong; it is the threshold that defines triple-negative disease.

In 196 women with triple-negative breast cancer left with residual tumour after pre-surgery chemotherapy, finding tumour DNA in the blood after surgery tripled the risk of distant relapse and quadrupled the risk of death; at two years 56 percent versus 81 percent were free of distant disease.

The US oncology society's 2022 rules on which tests to run before choosing drugs for metastatic breast cancer: PD-L1 for pembrolizumab, germline BRCA for PARP inhibitors, and no routine test for TROP2 or for tumour DNA in blood.

The 2026 journal summary of the US NCCN breast cancer guideline, this version focused on recurrent and metastatic disease and how treatment is chosen by receptor status, prior therapy and time since treatment.

The 812-patient trial in which adding the AKT inhibitor capivasertib to first-line paclitaxel did not lengthen life in metastatic triple-negative breast cancer (17.7 versus 18.0 months), even in the 31 percent of patients whose tumours carried the pathway alterations it targets.

A 2008 MD Anderson series showing that 57 percent of breast cancers in BRCA1 carriers were triple-negative against 14 percent in women without a BRCA fault, the clinical number behind the rule that triple-negative diagnosis should prompt a genetic test.

A 3,689-patient study showing that 36.6 percent of triple-negative tumours are HER2-low, that in triple-negative disease HER2-low tumours are biologically no different from HER2-zero ones, and that pathologists agree poorly on the score; the label matters only because a drug now depends on it.

Black women in the United States have about twice the odds of a triple-negative diagnosis and, in the UK POSH cohort, worse survival than White women despite equal chemotherapy use. The pivotal trials enrolled few of them. Enrolment targets tied to incidence, reported by ethnicity in every primary paper, would make the evidence match the disease.

The Oxford overview of 123 trials and 100,000 women showing that anthracycline and taxane chemotherapy cuts breast cancer deaths by about a third, largely regardless of age, nodes, size, grade or hormone receptor status; it is the foundation triple-negative chemotherapy rests on.

A 2015 Baylor study of 198 triple-negative tumours that found four stable subtypes, luminal androgen receptor, mesenchymal, basal-like immune-suppressed and basal-like immune-activated, with the immune-activated group faring best and the immune-suppressed worst.

After pre-surgery chemotherapy leaves tumour behind, a blood test for tumour DNA triples the risk of distant relapse when positive. The one trial that acted on it found the DNA usually appeared too late. A trial that tests at surgery with a tumour-informed assay, escalates positives to an antibody-drug conjugate and observes negatives has not been run.

The trial of 644 women with newly metastatic triple-negative breast cancer who could not have immunotherapy, in which the antibody-drug conjugate datopotamab deruxtecan held the cancer still for 10.8 months against 5.6 with chemotherapy and lengthened life from 18.7 to 23.7 months.

The 2007 population study of 6,370 Californian women that fixed the demographics of triple-negative breast cancer: younger, more often Black or Hispanic, poorer, diagnosed later and with worse survival at every stage; Black women with late-stage disease had 14 percent five-year survival.

The European oncology society's 2024 guideline for breast cancer that has not spread, covering diagnosis, surgery, radiotherapy, drug treatment before and after surgery, and follow-up; the reference standard for European and UK care of early triple-negative disease.

The European oncology society's 2021 guideline for breast cancer that has spread, the parent document of the living guideline that is now updated as trials read out.

The UK cohort of 2,915 women diagnosed with breast cancer at 40 or younger in which Black women had more triple-negative tumours (26 versus 19 percent) and worse survival despite the same access to care and the same use of chemotherapy.

The one UK study to look found young Black women had more triple-negative breast cancer and worse survival than White women despite equal chemotherapy, but it ended in 2008 and covered women under 41. Routine cancer statistics could report triple-negative incidence, stage and survival by ethnicity every year; at present they do not.

A 2000 study of 66 Polish families with breast and ovarian cancer in which three BRCA1 mutations accounted for more than four in five of the faults found, showing that a short national test panel could replace full gene sequencing in Poland.

The 2001 follow-up showing that the gene-expression groups of breast cancer predict how patients fare, with the basal-like group doing worst; it made the subtypes clinical rather than descriptive.

A 2003 study using an ordinary pathology stain, cytokeratin 5/6, to show that breast cancers in women with an inherited BRCA1 fault are nine times more likely to have the basal pattern; it brought the basal-like idea from the microarray to the pathology bench.

Two thirds of women treated on the KEYNOTE-522 regimen have no tumour left at surgery and about 92 percent of them are alive without relapse at five years, yet all receive nine more cycles of pembrolizumab. Trials are now testing whether the best responders can stop early, skip the anthracycline, or in lymphocyte-rich stage I tumours skip chemotherapy altogether.

Three PD-L1 tests run on the same tumours called 46, 75 and 73 percent of them positive and agreed only 69 percent of the time. With atezolizumab withdrawn, pembrolizumab's test (22C3, combined positive score of 10) is the only one that matters, yet laboratories still run whichever kit they have. One assay, one score and a proficiency scheme would end answers that vary by postcode.

The 2011 Vanderbilt analysis of 587 triple-negative tumours that split the disease into six molecular groups, two basal-like, an immune group, two mesenchymal groups and a luminal androgen receptor group, and matched each to cell lines and candidate drugs.

The US trial of 443 women that showed adding carboplatin to pre-surgery paclitaxel, doxorubicin and cyclophosphamide raised complete tumour disappearance in breast and nodes from 41 to 54 percent, at the cost of more low blood counts and skipped doses; it and GeparSixto made platinum standard.

The 4.5-year follow-up of BrighTNess showing that adding carboplatin to pre-surgery chemotherapy in 634 women cut relapse or death by about 40 percent without more second cancers, while adding the PARP inhibitor veliparib added nothing.

The 2017 validation of the residual cancer burden score, which graded how much triple-negative tumour is left after pre-surgery chemotherapy and found ten-year relapse-free survival of 86 percent with no residual tumour, 81 percent with minimal, 55 percent with moderate and 23 percent with extensive residual disease.

The 2020 joint US guideline for breast cancer in people who carry an inherited fault in BRCA1, BRCA2 or another risk gene: breast-conserving surgery is allowed, bilateral mastectomy should be discussed, platinum beats taxanes in advanced disease and PARP inhibitors beat single-agent chemotherapy.

The 2000 study that read the activity of 8,102 genes in 65 breast tumours and found the tumours fell into distinct groups, one of them the basal-like group that most triple-negative cancers belong to.

The US oncology society's 2021 rules for treatment before surgery: triple-negative tumours of 1 cm or more, or with involved nodes, should get anthracycline and taxane chemotherapy, carboplatin may be added, and at that date the evidence for adding immunotherapy was judged insufficient.

The second planned analysis of OlympiA, at 3.5 years, in which a year of olaparib tablets after standard treatment cut deaths by 32 percent in women with an inherited BRCA fault, the first time a PARP inhibitor had lengthened life in early breast cancer.

The US regulator's pooled analysis of 11,955 patients in 12 trials that found complete disappearance of the tumour before surgery predicts survival most strongly in triple-negative disease, but that a trial raising the complete response rate does not reliably improve survival.

Three different PD-L1 tests run on the same 614 IMpassion130 tumours called 46, 75 and 73 percent of them positive and agreed with each other only about 69 percent of the time; the benefit of atezolizumab was concentrated in the tumours all three called positive.

The 2006 North Carolina study that found the basal-like subtype in 39 percent of breast cancers in premenopausal African American women against 16 percent in other women, offering a biological reason for the worse survival of young Black women with breast cancer.

The 2016 revision that cut the six triple-negative subtypes to four after showing the immune and stem-like signals came from surrounding cells, and found that response to standard chemotherapy before surgery ranged from 41 percent in basal-like 1 to 18 percent in basal-like 2.

About a third of triple-negative tumours are HER2-low and so eligible for trastuzumab deruxtecan, but the difference between a HER2 score of 0 and 1+ is the one pathologists agree on least, and most triple-negative tumours were scored before the label mattered. Re-scoring archived slides with digital help when a patient relapses would find the eligible third.

The 2003 paper that found the same breast cancer subtypes in other laboratories' data and showed that tumours from women with an inherited BRCA1 fault fall into the basal-like group, linking hereditary and triple-negative disease.

A pooled analysis of 5,161 patients from 12 European and US institutions and trials confirming that the residual cancer burden score predicts relapse in every breast cancer subtype, and proposing it become part of standard pathology reporting after pre-surgery chemotherapy.

The 2008 MD Anderson series of 1,118 women that defined the triple-negative paradox: these tumours disappear completely with pre-surgery chemotherapy twice as often as other breast cancers, yet survival is worse, because the women left with residual disease relapse early and often.

The UK trial that watched 161 women with early triple-negative breast cancer by three-monthly blood tests for tumour DNA: 27 percent tested positive within a year, but by then nearly three quarters already had visible metastases, and none of the five who started pembrolizumab cleared the DNA. The lesson was to test earlier and more sensitively.

A 2008 Dana-Farber series of 116 women with metastatic triple-negative breast cancer in which 46 percent developed brain metastases before death, median survival after spread was 13.3 months and after a brain diagnosis 4.9 months.

The final GeparSixto report: adding carboplatin before surgery cut relapse in triple-negative disease by 44 percent, and a DNA-repair deficiency score predicted which tumours would disappear, though it did not predict who gained from the platinum.

The six-year OlympiA update: the year of olaparib still cut relapse by 35 percent and death by 28 percent, six-year survival was 87.5 versus 83.2 percent, there were fewer new BRCA-related breast and ovarian cancers, and no excess of leukaemia.

The 2025 international consensus on early breast cancer, which recommends platinum chemotherapy and immunotherapy for triple-negative disease, updated genetic testing guidance and shorter radiotherapy schedules.

The 1997 study of 5,318 Ashkenazi Jewish volunteers that measured the real-world breast cancer risk of the three founder mutations carried by more than 2 percent of that population: 56 percent by age 70, lower than the 85 percent estimated from high-risk families.

Nearly half of women with metastatic triple-negative breast cancer develop brain metastases and survive under five months after the diagnosis, yet the trials that set the standard mostly exclude active brain disease. Requiring a brain metastasis cohort in every phase 3, with intracranial response as an endpoint, would answer whether the new drugs reach the brain.

The 2007 Toronto study that gave triple-negative breast cancer its clinical portrait: 11 percent of cases, a risk of distant relapse 2.6 times higher than other breast cancers, a peak at three years and then a fall, so that women who reach five years without relapse are largely safe.

A pooled study of 1,966 women with early triple-negative breast cancer treated with surgery and radiotherapy but no chemotherapy, in which those whose tumours were half or more immune cells had 94 percent five-year freedom from distant relapse in stage I disease against 78 percent for immune-poor tumours.

The 2023 report of the international expert panel that meets every two years to vote on how early breast cancer should be treated, this time stressing multidisciplinary decisions and the right intensity and duration of treatment.

A count of 1.15 million US breast cancers from 2010 to 2014 in which Black women had 2.27 times the odds of a triple-negative diagnosis and women under 40 nearly twice the odds, confirming the disparity at national scale.

A 2025 letter recording the latest changes to Europe's continuously updated guideline for metastatic breast cancer, the mechanism through which first-line antibody-drug conjugate results enter European practice.

The first US national count of breast cancer by receptor subtype, from 2010 when cancer registries began recording HER2: 12.2 percent of cases were triple-negative, and Black women had the highest rate of that subtype.

The 2022 fast-track amendment in which the US oncology society added pembrolizumab before and after surgery for high-risk early triple-negative breast cancer, a year after its main guideline had said the evidence was insufficient.