{"entity":{"id":"tnbc-early","kind":"cancer","name":"Early triple-negative breast cancer","aka":["Stage I to III triple-negative breast cancer","Operable triple-negative breast cancer","Curable TNBC"],"tldr":"Early triple-negative breast cancer is treated to cure. For tumours over 2 cm or with node involvement, chemotherapy plus the immunotherapy pembrolizumab before and after surgery has raised cure rates; BRCA carriers with cancer left at surgery add a year of olaparib, and others with residual cancer are offered capecitabine. Whether the tumour has vanished by surgery guides what comes next.","summary":"Early triple-negative disease is basal-like in most cases, almost always TP53-mutant, carries a germline BRCA1 or BRCA2 mutation in roughly one in five patients and is the breast cancer with the most immune infiltration. Because there is no receptor to block, chemotherapy has carried the curative burden, and it is given before surgery whenever the tumour is over 2 cm or the nodes are involved, both to shrink it and because the response at surgery, measured as pathological complete response or residual cancer burden, is the strongest predictor of relapse. Platinum added to a taxane and anthracycline raised complete response rates in GeparSixto, CALGB 40603 and BrighTNess, and tumours under 1 cm without node involvement often need no chemotherapy at all, with high tumour-infiltrating lymphocytes marking a group whose outcome is excellent regardless.\n\nKEYNOTE-522 rewrote the standard. It randomised 1,174 patients with stage II or III disease to pembrolizumab or placebo with carboplatin and paclitaxel then an anthracycline and cyclophosphamide before surgery, followed by pembrolizumab or placebo for nine cycles after. Pathological complete response rose from 51.2 to 64.8 percent, event-free survival improved (hazard ratio 0.63) and, unusually for a neoadjuvant trial, overall survival did too, with the seven-year update showing 85.1 against 77.2 percent alive; the FDA approved the regimen in July 2021 and it is given whatever the PD-L1 score. IMpassion031 showed atezolizumab raises complete response in the same setting (58 against 41 percent) but never became a standard.\n\nWhat follows surgery depends on what the pathologist finds. Women with a complete response finish their year of pembrolizumab and whether they need it at all is being tested in OptimICE-pCR. Women with residual disease and a germline BRCA mutation take olaparib for a year: OlympiA randomised 1,836 such patients with HER2-negative disease, about four in five triple-negative, and improved invasive disease-free survival (hazard ratio 0.58) and overall survival (hazard ratio 0.72). Others are offered six to eight cycles of capecitabine on the strength of CREATE-X, a Japanese trial of 910 women with residual HER2-negative disease in which five-year disease-free survival rose from 67.6 to 74.1 percent with the largest survival gain in the triple-negative group. None of these post-surgery trials included pembrolizumab, so how the pieces combine is unknown, and ASCENT-05 is testing sacituzumab govitecan with pembrolizumab in residual disease while SCARLET asks whether the anthracycline can be dropped and circulating tumour DNA is being studied to find the women who still harbour disease.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Triple-negative_breast_cancer","links":[{"label":"KEYNOTE-522 (NEJM 2020)","url":"https://doi.org/10.1056/NEJMoa1910549"},{"label":"KEYNOTE-522 overall survival (NEJM 2024)","url":"https://doi.org/10.1056/NEJMoa2409932"},{"label":"OlympiA (NEJM 2021)","url":"https://doi.org/10.1056/NEJMoa2105215"},{"label":"CREATE-X (NEJM 2017)","url":"https://doi.org/10.1056/NEJMoa1612645"}],"tags":["subtype-page"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity"],"keyPapers":["paper-olympia-nejm-2021"],"journals":[],"dependsOn":[],"notes":[],"group":"breast","burden":"Most of the roughly 200,000 triple-negative breast cancers diagnosed each year are found before they have spread; relapses cluster in the first three years, so what happens around surgery decides most outcomes.","subtypes":["Stage I, node-negative basal-like tumours of 2 cm or less (chemotherapy without immunotherapy, or none for the smallest)","Stage II to III triple-negative disease (KEYNOTE-522 population)","Germline BRCA1 or BRCA2-mutant early triple-negative disease (OlympiA)","Residual invasive disease after neoadjuvant therapy (capecitabine, olaparib, trials)","Pathological complete response after neoadjuvant chemo-immunotherapy","Immunomodulatory triple-negative disease with high tumour-infiltrating lymphocytes"],"biomarkers":["Oestrogen and progesterone receptor under 1 percent and HER2 0 to 1+, or 2+ without amplification","Germline BRCA1, BRCA2 and PALB2 (olaparib eligibility, surgical choices)","Tumour-infiltrating lymphocytes (prognostic, de-escalation trials)","Pathological complete response and residual cancer burden at surgery","PD-L1 (not required for pembrolizumab in early disease)","Circulating tumour DNA after surgery (investigational)"],"standardOfCare":[{"setting":"Stage I, tumours 2 cm or less without node involvement","approach":"Surgery with sentinel node biopsy and radiotherapy; chemotherapy for tumours over 1 cm, often omitted below that, with tumour-infiltrating lymphocytes guiding de-escalation trials.","refs":["lumpectomy","sentinel-node","hypofractionated-radiotherapy","tils"]},{"setting":"Stage II to III, before surgery","approach":"Pembrolizumab with carboplatin and paclitaxel, then with doxorubicin or epirubicin and cyclophosphamide, followed by surgery (KEYNOTE-522).","refs":["pembrolizumab","carboplatin","paclitaxel","doxorubicin","epirubicin","cyclophosphamide","keynote-522","checkpoint-inhibitor"]},{"setting":"After surgery, pathological complete response","approach":"Pembrolizumab to complete a year and radiotherapy by stage; omission of adjuvant pembrolizumab is under test (OptimICE-pCR).","refs":["pembrolizumab","pcr","optimice-pcr"]},{"setting":"After surgery, residual disease","approach":"Pembrolizumab to complete a year; olaparib for one year in germline BRCA carriers (OlympiA); capecitabine for six to eight cycles otherwise (CREATE-X); sacituzumab govitecan with pembrolizumab under study (ASCENT-05).","refs":["pembrolizumab","olaparib","olympia","capecitabine","rcb","ascent-05","germline-testing"]},{"setting":"Local therapy","approach":"Breast conservation with whole-breast radiotherapy or mastectomy, sentinel node biopsy after neoadjuvant therapy, and post-mastectomy radiotherapy for node-positive disease.","refs":["lumpectomy","mastectomy","sentinel-node","imrt-igrt"]}],"stateOfArt":["Chemo-immunotherapy before and after surgery improves survival, the first curative gain in triple-negative disease in a generation.","Adjuvant olaparib for BRCA carriers makes germline testing part of every treatment plan.","Response-adapted treatment after surgery, with capecitabine or olaparib for residual disease.","De-escalation for small, lymphocyte-rich tumours is moving from cohorts into trials."],"history":[{"year":2007,"title":"Triple-negative defined as a clinical entity","refs":[]},{"year":2014,"title":"GeparSixto and CALGB 40603: carboplatin raises pathological complete response","refs":["carboplatin"]},{"year":2017,"title":"CREATE-X: capecitabine for residual disease after neoadjuvant chemotherapy","refs":["capecitabine"]},{"year":2020,"title":"KEYNOTE-522 and IMpassion031: immunotherapy raises pathological complete response","refs":["keynote-522","impassion031","pembrolizumab","atezolizumab"]},{"year":2021,"title":"Pembrolizumab approved for early disease; OlympiA adjuvant olaparib","refs":["pembrolizumab","olympia","olaparib"]},{"year":2024,"title":"KEYNOTE-522 overall survival benefit published","refs":["keynote-522"]}],"pipeline":["ascent-05","optimice-pcr","scarlet-s2212","mrd-testing","sacituzumab-govitecan","neoantigen-mrna-vaccine","tils"],"openProblems":["No trial has tested capecitabine or olaparib on top of adjuvant pembrolizumab for residual disease.","About a third of patients do not reach a complete response and most relapses come from them.","Immune-related endocrine side effects are permanent in a few percent of women who would have been cured anyway.","Black women have twice the incidence and worse outcomes, and trial enrolment does not reflect this."],"parent":"tnbc"},"route":"/cancers/tnbc-early/","neighbours":{"bottleneck":[{"id":"b-trial-diversity","kind":"bottleneck","name":"Trials do not represent the people who get cancer","route":"/bottlenecks/b-trial-diversity/"}],"paper":[{"id":"paper-olympia-nejm-2021","kind":"paper","name":"OlympiA: a year of olaparib after surgery for BRCA-mutated, high-risk early breast cancer","route":"/key-papers/paper-olympia-nejm-2021/"}],"drug":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"epirubicin","kind":"drug","name":"Epirubicin","route":"/drugs/epirubicin/"},{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"}],"trial":[{"id":"ascent-05","kind":"trial","name":"ASCENT-05 / OptimICE-RD (AFT-65, GBG 119, NSABP B-63)","route":"/trials/ascent-05/"},{"id":"impassion031","kind":"trial","name":"IMpassion031","route":"/trials/impassion031/"},{"id":"keynote-522","kind":"trial","name":"KEYNOTE-522","route":"/trials/keynote-522/"},{"id":"olympia","kind":"trial","name":"OlympiA","route":"/trials/olympia/"},{"id":"optimice-pcr","kind":"trial","name":"OptimICE-pCR (A012103)","route":"/trials/optimice-pcr/"},{"id":"scarlet-s2212","kind":"trial","name":"SCARLET (SWOG S2212)","route":"/trials/scarlet-s2212/"}],"technology":[{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"},{"id":"hypofractionated-radiotherapy","kind":"technology","name":"Hypofractionated radiotherapy","route":"/technologies/hypofractionated-radiotherapy/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"},{"id":"neoantigen-mrna-vaccine","kind":"technology","name":"Personalised neoantigen (mRNA) vaccines","route":"/technologies/neoantigen-mrna-vaccine/"},{"id":"sentinel-node","kind":"technology","name":"Sentinel lymph node biopsy","route":"/technologies/sentinel-node/"}],"term":[{"id":"lumpectomy","kind":"term","name":"Lumpectomy (breast-conserving surgery)","route":"/terms/lumpectomy/"},{"id":"mastectomy","kind":"term","name":"Mastectomy","route":"/terms/mastectomy/"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"},{"id":"rcb","kind":"term","name":"Residual cancer burden (RCB)","route":"/terms/rcb/"},{"id":"tils","kind":"term","name":"Tumour-infiltrating lymphocytes (TILs)","route":"/terms/tils/"}],"cancer":[{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}]}}