{"slug":"tnbc","tag":"tnbc","variants":["tnbc"],"description":"No description yet","count":35,"kinds":{"cancer":12,"term":19,"roadmap":1,"person":3},"related":[{"slug":"breast","tag":"breast","shared":32},{"slug":"subtype-page","tag":"subtype-page","shared":12},{"slug":"immunotherapy","tag":"immunotherapy","shared":2},{"slug":"biomarkers","tag":"biomarkers","shared":1},{"slug":"platform-trial","tag":"platform-trial","shared":1},{"slug":"roadmap","tag":"roadmap","shared":1},{"slug":"surgery","tag":"surgery","shared":1},{"slug":"trialist","tag":"trialist","shared":1}],"records":[{"id":"tnbc-basal-like-1","kind":"cancer","name":"Basal-like 1 triple-negative breast cancer (BL1)","route":"/cancers/tnbc-basal-like-1/","tldr":"Basal-like 1 is the subtype of triple-negative breast cancer whose cancer cells are busiest dividing and worst at repairing DNA. In the studies that defined it, these tumours were the most likely to disappear completely with chemotherapy before surgery, about four in ten, and their cell lines responded best to platinum drugs."},{"id":"tnbc-basal-like-2","kind":"cancer","name":"Basal-like 2 triple-negative breast cancer (BL2)","route":"/cancers/tnbc-basal-like-2/","tldr":"Basal-like 2 is a subtype of triple-negative breast cancer that shares the basal identity of basal-like 1 but is driven more by growth-factor signalling than by DNA damage, and it responded worst to standard chemotherapy before surgery in the studies that defined it, with pathological complete response in about one in five patients or fewer."},{"id":"tnbc-mesenchymal","kind":"cancer","name":"Mesenchymal triple-negative breast cancer (M)","route":"/cancers/tnbc-mesenchymal/","tldr":"Mesenchymal triple-negative breast cancers have switched on the programme cells use to migrate (epithelial-to-mesenchymal transition). They overlap with claudin-low and metaplastic tumours, respond to chemotherapy less well than basal-like 1 tumours, and are the subtype the parent page names as resisting every drug class."},{"id":"tnbc-mesenchymal-stem-like","kind":"cancer","name":"Mesenchymal stem-like triple-negative breast cancer (MSL)","route":"/cancers/tnbc-mesenchymal-stem-like/","tldr":"Mesenchymal stem-like was one of the six original subtypes of triple-negative breast cancer, marked by stem-cell and low-proliferation genes. Five years later the same group showed the signal came from stromal cells mixed into the sample rather than the cancer cells, so the label describes a tumour environment rather than a tumour."},{"id":"tnbc-luminal-androgen-receptor","kind":"cancer","name":"Luminal androgen receptor triple-negative breast cancer (LAR)","route":"/cancers/tnbc-luminal-androgen-receptor/","tldr":"Luminal androgen receptor cancers are triple-negative breast cancers that behave like hormone-driven tumours run by the male hormone receptor instead of oestrogen. They are less proliferative, respond less well to chemotherapy, and have shown modest benefit from prostate cancer drugs that block the androgen receptor in phase 2 trials; none is approved for breast cancer."},{"id":"tnbc-immunomodulatory","kind":"cancer","name":"Immunomodulatory triple-negative breast cancer (IM)","route":"/cancers/tnbc-immunomodulatory/","tldr":"Immunomodulatory triple-negative breast cancers are the ones packed with immune cells. The 2016 re-analysis showed the signature comes from those lymphocytes rather than the tumour, so today the same idea is captured by counting tumour-infiltrating lymphocytes on the biopsy, which predicts a better outcome and is used to test whether some small tumours need less treatment."},{"id":"metaplastic-breast-carcinoma","kind":"cancer","name":"Metaplastic breast carcinoma","route":"/cancers/metaplastic-breast-carcinoma/","tldr":"Metaplastic breast cancer is a rare form in which part of the tumour has changed into another tissue type, such as squamous skin-like cells, spindle cells or bone and cartilage. Most are triple-negative and they do worse than other triple-negative cancers, resisting chemotherapy; the low-grade forms are an exception with an excellent outlook."},{"id":"medullary-pattern-breast-carcinoma","kind":"cancer","name":"Carcinoma with medullary pattern (medullary breast cancer)","route":"/cancers/medullary-pattern-breast-carcinoma/","tldr":"Medullary breast cancers are high-grade, triple-negative tumours with a sharp border and a heavy immune-cell infiltrate that, despite looking aggressive, do better than ordinary breast cancers of the same grade. They are linked to BRCA1. Pathologists now call them a medullary pattern of common breast cancer rather than a type of their own."},{"id":"adenoid-cystic-carcinoma-breast","kind":"cancer","name":"Adenoid cystic carcinoma of the breast","route":"/cancers/adenoid-cystic-carcinoma-breast/","tldr":"Adenoid cystic carcinoma of the breast is a very rare breast cancer that is triple-negative on testing but behaves almost the opposite of usual triple-negative disease: it seldom reaches the lymph nodes, and nearly everyone is alive at ten years. It is the same tumour type as adenoid cystic carcinoma of the salivary glands and shares its gene fusion."},{"id":"apocrine-carcinoma-breast","kind":"cancer","name":"Apocrine carcinoma of the breast","route":"/cancers/apocrine-carcinoma-breast/","tldr":"Apocrine breast cancers are made of large cells resembling sweat-gland cells. They lack oestrogen and progesterone receptors but carry the androgen receptor, so the triple-negative ones sit in the luminal androgen receptor group and are the tumours in which androgen-blocking drugs have been tried."},{"id":"secretory-carcinoma-breast","kind":"cancer","name":"Secretory carcinoma of the breast","route":"/cancers/secretory-carcinoma-breast/","tldr":"Secretory carcinoma is a very rare, slow-growing breast cancer first described in children, whose cells make milk-like secretions. It is usually triple-negative but almost always carries the ETV6-NTRK3 gene fusion, so the rare patient whose tumour spreads can be treated with an NTRK inhibitor tablet, and most need no chemotherapy."},{"id":"brca-associated-tnbc","kind":"cancer","name":"BRCA-associated triple-negative breast cancer","route":"/cancers/brca-associated-tnbc/","tldr":"Some triple-negative breast cancers arise because a person was born with a faulty BRCA1 or BRCA2 gene. This group is diagnosed younger, is found by a blood test NICE recommends for all women under 50 with triple-negative disease, and has options of its own: platinum chemotherapy works well, a year of olaparib lowers relapse, and surgery decisions weigh the risk of a second cancer."},{"id":"er-pr-negative-threshold","kind":"term","name":"ER and PR negative under 1 percent (the triple-negative threshold, and ER-low)","route":"/terms/er-pr-negative-threshold/","tldr":"A breast cancer counts as oestrogen receptor negative when fewer than 1 in 100 of its cells stain for the receptor, and the same rule applies to progesterone receptor. Tumours with 1 to 10 percent staining are labelled ER low positive, but they behave like triple-negative cancers and in some countries are treated as such."},{"id":"her2-low-and-trop2-adc-eligibility-tnbc","kind":"term","name":"HER2-low eligibility for trastuzumab deruxtecan, and TROP2 ADCs without a test (triple-negative disease)","route":"/terms/her2-low-and-trop2-adc-eligibility-tnbc/","tldr":"Two antibody-drug conjugates reach triple-negative breast cancer by different rules. Trastuzumab deruxtecan needs the tumour to show a little HER2 (a score of 1+, or 2+ without gene amplification), so the pathologist's call between 0 and 1+ matters. Sacituzumab govitecan targets TROP2, which almost all breast cancers carry, and is given without any test."},{"id":"pd-l1-cps-10-tnbc","kind":"term","name":"PD-L1 combined positive score 10 in triple-negative breast cancer","route":"/terms/pd-l1-cps-10-tnbc/","tldr":"In metastatic triple-negative breast cancer the immunotherapy pembrolizumab is only given when a PD-L1 stain of the tumour scores 10 or more on the combined positive score, because that is the group in which the trial showed people lived longer. For early disease before surgery no PD-L1 test is needed: pembrolizumab helped regardless."},{"id":"hrd-in-breast-cancer","kind":"term","name":"Homologous recombination deficiency (HRD) in breast cancer","route":"/terms/hrd-in-breast-cancer/","tldr":"Homologous recombination deficiency means a tumour cannot mend double-strand DNA breaks properly, most often because BRCA1 or BRCA2 is lost. About seven in ten triple-negative tumours score as deficient, and they respond better to platinum chemotherapy; but unlike ovarian cancer, no breast cancer drug is approved on the basis of an HRD score, only on a germline BRCA result."},{"id":"germline-brca-testing-criteria-tnbc","kind":"term","name":"Germline BRCA testing criteria for triple-negative breast cancer (UK)","route":"/terms/germline-brca-testing-criteria-tnbc/","tldr":"In the NHS a blood test for inherited BRCA1 and BRCA2 faults is offered to every woman under 50 with triple-negative breast cancer, whatever her family history, and hospital testing criteria now extend that to triple-negative disease under 60 and any breast cancer under 40. Others are tested when a calculator puts the chance of a family fault at 10 percent or more."},{"id":"ki-67-in-tnbc","kind":"term","name":"Ki-67 in triple-negative breast cancer","route":"/terms/ki-67-in-tnbc/","tldr":"Ki-67 is a stain that marks dividing cells. Triple-negative cancers almost all score high, typically around 60 percent, so the marker separates them from slower hormone-driven cancers but rarely changes treatment within the triple-negative group; the international working group limits its clinical use to hormone receptor-positive disease."},{"id":"basal-like","kind":"term","name":"Basal-like breast cancer","route":"/terms/basal-like/","tldr":"Basal-like is a breast cancer subtype defined by the genes its cells switch on, which resemble the basal cells lining the milk ducts. About four in five triple-negative cancers are basal-like and most basal-like cancers are triple-negative, but the two labels are not the same thing, and the overlap is where BRCA1-related cancers sit."},{"id":"claudin-low","kind":"term","name":"Claudin-low breast cancer","route":"/terms/claudin-low/","tldr":"Claudin-low breast cancers have lost the claudin proteins that hold epithelial cells together and have taken on the features of migrating, stem-like cells. Most are triple-negative and respond to chemotherapy less well than basal-like cancers. Newer work treats claudin-low as a pattern that can overlay any subtype rather than a subtype of its own."},{"id":"androgen-receptor-positive-tnbc","kind":"term","name":"Androgen receptor-positive triple-negative breast cancer","route":"/terms/androgen-receptor-positive-tnbc/","tldr":"Some triple-negative breast cancers carry the androgen receptor, the protein that prostate cancer runs on. About one in eight ER-negative cancers stain positive, and in trials the prostate drugs bicalutamide and enzalutamide held the disease for a minority of patients; neither is approved for breast cancer, so this remains a trial question."},{"id":"ajcc-prognostic-stage-breast","kind":"term","name":"AJCC 8th edition prognostic stage for breast cancer","route":"/terms/ajcc-prognostic-stage-breast/","tldr":"Since 2018 the American staging system gives breast cancer two stages: the anatomic stage from tumour size, nodes and spread, and a prognostic stage that also counts grade and the three receptors. Because triple-negative cancers are usually grade 3 and receptor negative, their prognostic stage is often a step higher than their anatomic stage; UK pages and NICE quote the anatomic TNM stage."},{"id":"interval-breast-cancer","kind":"term","name":"Interval breast cancer (a cancer found between screening rounds)","route":"/terms/interval-breast-cancer/","tldr":"An interval breast cancer is one diagnosed after a normal screening mammogram and before the next invitation. Fast-growing cancers, triple-negative disease among them, make up a larger share of interval than of screen-detected cancers, which is why a new breast change should always be checked rather than left until the next screen."},{"id":"risk-reducing-surgery-brca-carriers","kind":"term","name":"Risk-reducing surgery for BRCA carriers (bilateral and contralateral mastectomy, salpingo-oophorectomy)","route":"/terms/risk-reducing-surgery-brca-carriers/","tldr":"Women who carry a BRCA1 or BRCA2 fault can choose to have both breasts removed before any cancer appears, which cuts breast cancer risk by about nine tenths, or to remove the other breast after a first cancer. Removing the ovaries protects against ovarian cancer but, in the largest prospective study, did not lower breast cancer risk in BRCA1 carriers."},{"id":"chemoprevention-and-er-negative-breast-cancer","kind":"term","name":"Chemoprevention (tamoxifen, anastrozole, raloxifene) and ER-negative breast cancer","route":"/terms/chemoprevention-and-er-negative-breast-cancer/","tldr":"Tamoxifen and anastrozole taken for five years cut the number of new breast cancers in women at raised risk by a third to a half, and NICE offers them to women at high or moderate risk. But the cancers they prevent are oestrogen-driven ones; in the trials they made no difference to oestrogen receptor-negative cancers, the kind BRCA1 carriers mostly get."},{"id":"founder-mutation","kind":"term","name":"Founder mutation (BRCA1 185delAG and 5382insC, BRCA2 6174delT)","route":"/terms/founder-mutation/","tldr":"A founder mutation is a single inherited gene fault that many people in one population share because they descend from the same ancestor who carried it. The best known are three BRCA faults carried by about one in forty Ashkenazi Jews, which is why Jewish ancestry is one of the family history flags in UK genetics referral rules."},{"id":"idfs","kind":"term","name":"Invasive disease-free survival (iDFS)","route":"/terms/idfs/","tldr":"Invasive disease-free survival is the yardstick of most trials that treat early breast cancer after surgery. A patient counts as an event if the cancer comes back anywhere as invasive disease, a new invasive cancer appears in either breast or elsewhere, or she dies of any cause; it deliberately ignores non-invasive recurrences. OlympiA used it to show that a year of olaparib helped BRCA carriers."},{"id":"luminal-androgen-receptor","kind":"term","name":"Luminal androgen receptor (LAR) subtype","route":"/terms/luminal-androgen-receptor/","tldr":"Luminal androgen receptor is one of the four molecular subtypes of triple-negative breast cancer. Its cells look and behave like hormone-driven luminal cells but run on the androgen receptor instead of oestrogen, which makes them slower growing, less responsive to chemotherapy and the target of trials with prostate cancer drugs."},{"id":"pd-l1-assay-discordance","kind":"term","name":"PD-L1 assay discordance (SP142, SP263 and 22C3 in breast cancer)","route":"/terms/pd-l1-assay-discordance/","tldr":"Three commercial PD-L1 stains give different answers on the same breast tumour: the SP142 assay used with atezolizumab called fewer than half of tumours positive while the 22C3 and SP263 assays called about three quarters. Because the pembrolizumab licence rests on 22C3 combined positive score 10, which test a laboratory runs, and how it scores it, decides who is offered immunotherapy."},{"id":"exceptional-responder","kind":"term","name":"Exceptional responder","route":"/terms/exceptional-responder/","tldr":"An exceptional responder is a patient whose cancer shrinks or stays controlled far longer than expected on a treatment that helps few people. The US National Cancer Institute defined the term for a study that sequenced such patients' tumours to learn why, and found a plausible molecular reason in about a quarter of them."},{"id":"health-disparities","kind":"term","name":"Health disparities in cancer outcomes (ethnicity, deprivation and access)","route":"/terms/health-disparities/","tldr":"Health disparities are differences in who gets a cancer and who survives it that track ethnicity, income and access to care rather than chance. Triple-negative breast cancer is the textbook case: Black women get it about twice as often, present later and die of it more often, and how much is biology and how much is unequal care is still being worked out on both sides of the Atlantic."},{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/","tldr":"Triple-negative breast cancer was named for what it lacks, the three receptors other breast cancers are treated through. This roadmap follows it from the receptor discoveries and the basal-like signature of 2000, through chemotherapy, platinum, PARP inhibitors, immunotherapy and antibody-drug conjugates, to the trials asking who can have less and who needs more, with registry dates to 2030."},{"id":"peter-schmid","kind":"person","name":"Peter Schmid","route":"/people/peter-schmid/","tldr":"Led KEYNOTE-522 and IMpassion130, the trials that brought immunotherapy into triple-negative breast cancer."},{"id":"lajos-pusztai","kind":"person","name":"Lajos Pusztai","route":"/people/lajos-pusztai/","tldr":"Translational breast oncologist who co-leads the I-SPY2 platform trial and helped show immunotherapy works in early TNBC."},{"id":"elizabeth-mittendorf","kind":"person","name":"Elizabeth A. Mittendorf","route":"/people/elizabeth-mittendorf/","tldr":"Surgeon-scientist who led IMpassion031 and studies of surgery de-escalation after neoadjuvant immunotherapy."}]}