OnCo
cancersCancer

Triple-negative breast cancer (TNBC)

A breast cancer that lacks the three receptors (oestrogen, progesterone, HER2) that other breast cancers can be treated through. It was the hardest subtype for decades; since 2020 immunotherapy and ADCs have changed that.

TNBC is defined by what it lacks: ER <1%, PR <1%, HER2 0-1+ (or 2+/ISH-negative). It is biologically heterogeneous (basal-like 1 and 2, mesenchymal, luminal androgen receptor, immunomodulatory subtypes), nearly always TP53-mutant, frequently HRD-positive (~20% germline BRCA1/2), and has the highest TROP2 expression and the most immune infiltration of any breast subtype. Relapses cluster in the first three years and favour visceral and brain metastases.

The standard of care changed three times in six years. KEYNOTE-522 (2020-21) made pembrolizumab plus carboplatin-containing chemotherapy before surgery, continued after, the standard for stage II-III disease, with a 7.9-point overall survival gain at seven years. OlympiA (2021) added adjuvant olaparib for germline BRCA carriers with residual disease. In metastatic disease, pembrolizumab-chemotherapy (CPS ≥10) was joined by the TROP2 ADCs: sacituzumab govitecan (ASCENT, second line 2020; first-line ASCENT-03/04 2026) and datopotamab deruxtecan (TROPION-Breast02, first-line PD-1-ineligible, 2026, with an overall survival benefit), while T-DXd covers the ~35% of TNBC that is HER2-low. The EGFR×HER3 bispecific ADC iza-bren posted the first positive phase 3 for a bispecific ADC in pretreated TNBC in February 2026.

What remains unsolved: residual disease after KEYNOTE-522 (RCB II-III) still carries ~40-50% relapse risk; ADC sequencing (TOP1-payload cross-resistance) is unstudied; PD-L1-negative early disease has no immunotherapy option; brain metastases; and the biology of the mesenchymal/claudin-low subtype resists every class. The most promising directions are ADC + IO first line, de-escalation guided by TILs and pCR, ctDNA-guided escalation, TROP2 PET selection, next-generation ADCs with non-TOP1 or dual payloads, and personalised vaccines in the adjuvant setting.

State of the art today

  • Curative-intent: chemo-immunotherapy (KEYNOTE-522) cures more patients than ever; pCR ~65%. Adjuvant PARP inhibitor for BRCA carriers.
  • HER2-low reclassification gives a third of TNBC patients access to T-DXd.
  • De-escalation is real: TIL-guided omission of chemotherapy in stage I; anthracycline-free and pembrolizumab-omission trials in stage II-III.
Show survival figures (1)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

  • Metastatic: ADCs first line (sacituzumab, Dato-DXd), ADC + IO for PD-L1+ disease; median OS in first-line trials now approaches two years, roughly double the 2015 figure.
Who it affects

TNBC accounts for about 10-15% of breast cancers, roughly 200,000 cases per year worldwide, and is more common in younger women, Black women, and BRCA1 carriers.

Group
breast

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

Site: Breast (all subtypes) (shared total; subtype split not reported). World: 2,296,840 new cases, 666,103 deaths.

#CountryNew casesDeaths
1China357,16174,986
2United States of America274,37542,900
3India192,02098,337
4Brazil94,72822,189
5Japan91,91617,638
6Russian Federation78,83922,115
7Germany74,01620,601
8Indonesia66,27122,598
9France (metropolitan)65,65914,739
10United Kingdom58,75612,122

GLOBOCAN reports breast cancer as one site. TNBC is roughly 10-15% of cases; the figures shown are for all breast cancer.

Standard of care

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Stage I (T1a-b N0)

Surgery ± radiation; chemotherapy for ≥T1c; TIL-high tumours have >90% 5-year RFS even without chemotherapy (OPTimal, ETNA, TIL-CHOICE cohorts). De-escalation trials ongoing.

NCCN Guidelines: Breast Cancer
Sentinel lymph node biopsyHistopathology & immunohistochemistry
Stage II-III

Neoadjuvant pembrolizumab + carboplatin/paclitaxel → AC/EC, surgery, adjuvant pembrolizumab (KEYNOTE-522). Germline BRCA + residual disease: olaparib 1 year (OlympiA). Residual disease without BRCA: capecitabine (CREATE-X). Radiation per stage.

NCCN · Category 1, preferred: neoadjuvant pembroli…ESMO-MCBS · A (KEYNOTE-522); A (OlympiA)
KEYNOTE-522PembrolizumabCarboplatinOlaparibOlympiA
Metastatic, first line, PD-L1 CPS ≥10

Pembrolizumab + chemotherapy (KEYNOTE-355) or sacituzumab govitecan + pembrolizumab (ASCENT-04, approved 2026).

NCCN · Category 1, preferred: sacituzumab goviteca…ESMO-MCBS · 4 (KEYNOTE-355)
KEYNOTE-355ASCENT-04 / KEYNOTE-D19Sacituzumab govitecanPembrolizumab
Metastatic, first line, PD-L1 negative or PD-1 ineligible

Datopotamab deruxtecan (TROPION-Breast02, OS benefit) or sacituzumab govitecan (ASCENT-03), both approved 2026; PARP inhibitor if germline BRCA; chemotherapy.

NCCN · Category 1, preferred: sacituzumab goviteca…
TROPION-Breast02ASCENT-03Datopotamab deruxtecanOlaparib
Metastatic, later lines

Whichever TROP2 ADC was not used first (cross-resistance uncertain); T-DXd if HER2-low (DESTINY-Breast04); iza-bren where available; chemotherapy (eribulin, capecitabine); clinical trials.

ESMO-MCBS · 4 (ASCENT; re-scored 5 in the breast-cancer…
Trastuzumab deruxtecanIzalontamab brengitecanDESTINY-Breast04

Subtypes & biomarkers

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Subtypes
  • Basal-like 1 (BL1, DDR-deficient, platinum/PARP-sensitive)
  • Basal-like 2 (BL2, growth-factor signalling)
  • Mesenchymal / claudin-low (EMT, stem-like, chemoresistant)
  • Luminal androgen receptor (LAR, AR+, PIK3CA-mutant)
  • Immunomodulatory (high TILs, IO-responsive)
  • HER2-low TNBC (~35%, eligible for T-DXd)
Biomarkers clinicians test
  • PD-L1 (22C3 CPS ≥10 for metastatic pembrolizumab)
  • Germline BRCA1/2 and PALB2 (PARP inhibitors, surgery choices)
  • HRD score
  • TILs (prognostic; de-escalation trials)
  • HER2-low status (T-DXd eligibility)
  • TROP2 (not required for TROP2 ADCs; PET tracers in development)
  • Ki-67, grade
  • ctDNA/MRD (Signatera, investigational)
  • AR (LAR subtype trials)
  • TMB / MSI (rare, tumour-agnostic IO)

Target prevalence in this cancer

Target / alterationPrevalenceSource
TROP2
ASCENT benefit was independent of TROP2 IHC level
80-90%
PMC
FAP
>80%
Wikipedia
TP53
80-85%
cBioPortal (TCGA)
HER3
50-70%
Wikipedia
Nectin-4
50-60%
Wikipedia
ROR1
40-60%
Wikipedia
PD-L1
KEYNOTE-355 screening
35-40%
Wikipedia
HER2
30-40%
Nature
BRCA1 / BRCA2 (HRD)
BRCA1 predominant
15-20%
Wikipedia
PARP
~40-50% HRD by scar
15-20%
Wikipedia
Androgen receptor
10-15%
Wikipedia

How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.

History

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  1. 2000Molecular portraits define the basal-like subtype

    Perou and Sørlie's expression profiling separates basal-like from luminal breast cancers.

    RNA sequencing & expression profiling
  2. 2007'Triple-negative' enters clinical vocabulary

    Defined by absence of ER, PR, HER2; recognised as the subtype with the worst prognosis and no targeted therapy.

  3. 2014Carboplatin raises pCR

    GeparSixto and CALGB 40603 show platinum increases pathologic complete response.

    CarboplatinPlatinum agents
  4. 2018First immunotherapy signal

    IMpassion130: atezolizumab + nab-paclitaxel improves PFS in PD-L1+ metastatic TNBC (approval later withdrawn).

    IMpassion130Atezolizumab
  5. 2018PARP inhibitors in BRCA breast cancer

    OlympiAD and EMBRACA lead to olaparib and talazoparib approvals.

    OlaparibTalazoparib
  6. 2020Sacituzumab govitecan approved

    ASCENT: OS 12.1 vs 6.7 months in pretreated disease; first ADC for TNBC.

    ASCENTSacituzumab govitecan
  7. 2020Pembrolizumab + chemotherapy first line

    KEYNOTE-355 in CPS ≥10 disease.

    KEYNOTE-355
  8. 2021KEYNOTE-522 changes early-stage care

    Neoadjuvant/adjuvant pembrolizumab approved for stage II-III TNBC; OS benefit confirmed 2024.

    KEYNOTE-522Pembrolizumab
  9. 2021OlympiA: adjuvant olaparib

    One year of olaparib after standard therapy improves iDFS and OS in gBRCA carriers.

    OlympiA
  10. 2022HER2-low: T-DXd works in 'HER2-negative' disease

    DESTINY-Breast04 includes TNBC patients with HER2-low tumours.

    DESTINY-Breast04Trastuzumab deruxtecan
  11. 2025First-line ADC era begins

    ASCENT-03, ASCENT-04, and TROPION-Breast02 all positive; TROPION-Breast02 shows OS benefit.

    ASCENT-03ASCENT-04 / KEYNOTE-D19TROPION-Breast02
  12. 2026Bispecific ADC succeeds; first-line ADC approvals

    Iza-bren phase 3 positive (Feb 2026); FDA approves Dato-DXd and sacituzumab govitecan first line (Q2 2026).

    BL-B01D1-307Datopotamab deruxtecanSacituzumab govitecan

Pipeline

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Under reviewADC
Sacituzumab tirumotecan
Phase 3Bispecific ADC
Izalontamab brengitecan
Phase 3ADC
Patritumab deruxtecan
Phase 2ADC
Puxitatug samrotecan
Under reviewBispecific antibody (PD-1×VEGF)
Ivonescimab
Phase 1Bispecific ADC
AK146D1
TROPION-Breast05IZABRIGHT-Breast01OptimICE-pCR (A012103)SCARLET (SWOG S2212)TROP2 PETDual-payload ADCPersonalised neoantigen (mRNA) vaccinesMRD / molecular residual disease testing

Open problems

  • Residual disease after KEYNOTE-522: no approved escalation beyond capecitabine/olaparib; ctDNA-guided trials needed.
  • ADC sequencing: does a second TOP1-payload ADC work after the first? SATEEN/BRE-354 suggest limited efficacy; chemotherapy interposition debated.
  • Patient selection for TROP2 ADCs: IHC does not predict; TROP2 PET and ctDNA are candidates.
  • PD-L1-negative early disease has no immunotherapy option and no ADC yet in the curative setting.
  • Brain metastases (up to 30-45% of metastatic TNBC) remain undertreated; ADC CNS activity is emerging but unproven.
  • Mesenchymal/claudin-low biology (EMT, efflux pumps) resists chemotherapy, ADC payloads, and immunotherapy alike.
  • Disparities: Black women have twice the TNBC incidence and worse outcomes; trial enrolment does not reflect this.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Triple-negative breast cancer (TNBC)
condition: triple negative breast cancer
Open on ClinicalTrials.gov →

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Landmark trials in OnCo

ASCENTASCENT-03ASCENT-04 / KEYNOTE-D19ASCENT-05 / OptimICE-RD (AFT-65, GBG 119, NSABP B-63)BL-B01D1-307DESTINY-Breast04IMpassion130IMpassion131IZABRIGHT-Breast01KEYNOTE-355KEYNOTE-522OlympiAOptimICE-pCR (A012103)SCARLET (SWOG S2212)TROPION-Breast02TROPION-Breast03TROPION-Breast05WHEL (Women's Healthy Eating and Living)

Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Triple-negative breast cancer

Curated set · 23 questions

Newly diagnosed

  1. What exactly makes my cancer 'triple-negative', and was HER2 scored as 0, 1+, or 2+?
    Why: HER2-low (1+ or 2+ without amplification) tumours qualify for trastuzumab deruxtecan later; the difference between 0 and 1+ matters.
  2. Have I been referred for germline genetic testing (BRCA1/2, PALB2 and others)?
    Why: Guidelines recommend it for all TNBC. A BRCA result changes surgery options, opens PARP inhibitors, and matters for relatives.
  3. What is my clinical stage, and which imaging was used to determine it?
    Why: Stage decides whether treatment starts with surgery or with chemo-immunotherapy; PET/CT is often used for stage II-III.
  4. What was my tumour-infiltrating lymphocyte (TIL) score, and does it change my options?
    Why: Very small, TIL-rich tumours have excellent outcomes; TIL status is being used to de-escalate treatment in trials.
  5. Is fertility preservation relevant for me, and do we have time before treatment starts?
    Why: Chemotherapy can affect fertility; egg or embryo freezing needs to happen before the first cycle.

Before surgery (neoadjuvant)

  1. Will I receive pembrolizumab with chemotherapy before surgery, as in KEYNOTE-522, and if not, why not?
    Why: This regimen improved survival for stage II-III TNBC and is the standard of care for most patients.
  2. Which side effects of immunotherapy should I watch for, and who do I call at any hour?
    Why: Immune-related side effects (thyroid, colitis, adrenal) are treatable if caught early; some are permanent.
  3. Is there a clinical trial testing less chemotherapy (for example without anthracyclines) or a newer drug that I might join?
    Why: SCARLET and other trials test whether some of the toughest chemotherapy can be dropped without losing effect.
  4. Am I a candidate for scalp cooling, and does the centre offer it?
    Why: It preserves hair in about half of patients on taxane-based regimens.

After surgery

  1. Did I have a pathologic complete response (pCR), and if not, what was my residual cancer burden (RCB)?
    Why: pCR predicts a very good outlook; residual disease means extra treatment such as capecitabine or olaparib is discussed.
  2. If I carry a BRCA mutation and had residual disease, will I be offered a year of olaparib?
    Why: OlympiA showed adjuvant olaparib improves survival in this group.
  3. Will I continue pembrolizumab after surgery, and is there a trial testing whether I can stop early if I had a pCR?
    Why: OptimICE-pCR is testing whether the adjuvant year of immunotherapy is needed after a complete response.
  4. Is there a role for blood tests for circulating tumour DNA (MRD) in my follow-up, in a trial or otherwise?
    Why: ctDNA detects relapse months before scans; interventional trials are testing acting on it.
  5. What surveillance schedule will I have, and which symptoms should prompt an early call?
    Why: TNBC relapses cluster in the first three years; knowing what to report reduces delay.
  6. Can I get a structured exercise programme and a survivorship plan, including heart health checks?
    Why: Exercise improved survival in colon cancer trials and reduces fatigue; anthracyclines can affect the heart.

Metastatic

  1. What is my PD-L1 combined positive score (CPS) on the most recent biopsy?
    Why: CPS 10 or more opens pembrolizumab combinations, including with the ADC sacituzumab govitecan.
  2. Which first-line option do you recommend for me: sacituzumab govitecan, datopotamab deruxtecan, or immunotherapy plus chemotherapy, and why?
    Why: Two TROP2 ADCs were approved first-line in 2026 with different side-effect profiles (neutropenia and diarrhoea vs stomatitis and eye effects).
  3. Is my tumour HER2-low, making trastuzumab deruxtecan an option later?
    Why: About a third of TNBC is HER2-low; T-DXd is approved in that setting after chemotherapy.
  4. If one ADC stops working, what is the plan for the next one, given that they may share resistance?
    Why: Back-to-back ADCs with the same payload class often work less well; sequencing is an open question worth discussing.
  5. Was a new biopsy or liquid biopsy taken at progression to re-check receptors and look for a trial-matching mutation?
    Why: Receptor status can change; comprehensive genomic profiling can reveal rare targetable alterations.
  6. Which clinical trials, including bispecific ADCs and newer TROP2 ADCs, could I be eligible for here or at a referral centre?
    Why: Izalontamab brengitecan and sacituzumab tirumotecan are in phase 3 trials that may be recruiting.
  7. Have you screened for brain metastases, and how will we monitor for them?
    Why: Brain involvement is common in metastatic TNBC and is treated differently.
  8. What supportive-care and palliative-care resources can be involved now, not later?
    Why: Early palliative care improves quality of life and sometimes survival, alongside active treatment.

Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.

Everything relevant

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Direct links plus the targets, companies, and technologies of this cancer's products.

technologies

36
Allogeneic stem cell transplantationAntibody-drug conjugate (ADC)Bispecific ADCBispecific antibodiesCancer interception vaccinesCAR-T cell therapyCardio-oncologyChemoprevention & risk-reducing surgeryCytotoxic chemotherapyDietary supplements during cancer treatment: interactions and harmsDigital pathology & AIDual-payload ADCExercise & lifestyle oncologyExercise during chemotherapy and radiotherapyFAPI PETFasting and fasting-mimicking diets around chemotherapyFluorescence-guided surgeryGermline (hereditary) testingHistopathology & immunohistochemistryImmune checkpoint inhibitorsIntratumoural gene electrotransfer (IL-12 plasmid)Liquid biopsy (ctDNA)Mammography & tomosynthesisMirai (MIT breast cancer risk from mammograms)MRD / molecular residual disease testingOptical & fluorescence imagingPARP inhibitorsPARP PETPersonalised neoantigen (mRNA) vaccinesPlatinum agentsRadioligand therapy (beta emitters)RNA sequencing & expression profilingSentinel lymph node biopsyTopoisomerase-I inhibitors (and ADC payloads)TROP2 PETUltrasound

targets

19
Androgen receptorATRBRCA1 / BRCA2 (HRD)CD73 / adenosine axisEGFRFAPFolate receptor alphaHER2HER3LIV-1 (SLC39A6)Nectin-4PARPPD-1PD-L1ROR1TP53TROP2VEGF / VEGFRWEE1

drugs

23
Phase 1Bispecific ADC
AK146D1
ApprovedMonoclonal antibody (anti-PD-L1)
Atezolizumab · Tecentriq / Tecentriq Hybreza (SC)
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
Not mapped hereAlkylating agent (oxazaphosphorine prodrug)
Cyclophosphamide · Cytoxan / Endoxan
ApprovedADC
Datopotamab deruxtecan · Datroway
ApprovedCytotoxic chemotherapy (anthracycline)
Doxorubicin · Adriamycin
ApprovedMonoclonal antibody (anti-PD-L1)
Durvalumab · Imfinzi
Not mapped hereSynthetic halichondrin B analogue (microtubule dynamics inhibitor)
Eribulin · Halaven
Phase 2Theranostic pair (peptide radioligand)
FAP-2286 (177Lu / 68Ga)
NegativeSmall molecule (claimed PARP inhibitor)
Iniparib
Under reviewBispecific antibody (PD-1×VEGF)
Ivonescimab
Phase 3Bispecific ADC
Izalontamab brengitecan
ApprovedSmall-molecule PARP inhibitor
Olaparib · Lynparza
ApprovedCytotoxic chemotherapy (taxane)
Paclitaxel / nab-paclitaxel · Taxol / Abraxane
Phase 3ADC
Patritumab deruxtecan
Not mapped hereProtease-activated fluorescent imaging agent
Pegulicianine · Lumisight
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
Phase 2ADC
Puxitatug samrotecan
ApprovedADC
Sacituzumab govitecan · Trodelvy
Under reviewADC
Sacituzumab tirumotecan
EstablishedTumour-informed ctDNA MRD test
Signatera
ApprovedSmall-molecule PARP inhibitor
Talazoparib · Talzenna
ApprovedADC
Trastuzumab deruxtecan · Enhertu

companies

19
AkesoAstraZenecaBristol Myers SquibbCelldex TherapeuticsCircle PharmaDaiichi SankyoEisaiGilead Sciences (incl. Kite)LunitMerck & Co. (MSD)Mersana TherapeuticsNateraNovartisPfizer (incl. Seagen)Roche / GenentechSanofiSichuan Kelun-BiotechSummit TherapeuticsSystImmune / Sichuan Biokin

institutions

30
Alliance for Clinical Trials in OncologyBreast Cancer Research FoundationBreast Cancer TrialsBreast International Group (BIG)Cleveland Clinic Taussig Cancer InstituteDana-Farber Brigham Cancer CenterFudan University Shanghai Cancer CenterGEICAM Spanish Breast Cancer GroupGerman Breast Group (GBG)Guy's and St Thomas' NHS Foundation Trust / King's Health Partners Cancer CentreHospital General Universitario Gregorio MarañónIEO – European Institute of OncologyIndiana University Melvin and Bren Simon Comprehensive Cancer CenterInstitut CurieInstitut Jules BordetInstitut Paoli-CalmettesKorle Bu Teaching HospitalLagos University Teaching HospitalMays Cancer Center at UT Health San AntonioNRG OncologySalk Institute Cancer CenterSkåne University Hospital / Lund University Cancer CentreSOLTI Cancer Research GroupSWOG Cancer Research NetworkThe University of Kansas Cancer CenterTianjin Medical University Cancer Institute and HospitalUNC Lineberger Comprehensive Cancer CenterUNICANCERUniversity of Malaya Medical CentreVanderbilt-Ingram Cancer Center

pathways

5
DNA damage response & homologous recombinationEpithelial–mesenchymal transition & drug effluxp53 / RB / cell-cycle checkpointPD-1 / PD-L1 immune checkpoint & T-cell activationPI3K / AKT / mTOR

terms

9
ADC sequencingCancer health disparities and equityCombined positive score (CPS)HER2-low and HER2-ultralowHomologous recombination deficiency (HRD)PAM50 / intrinsic subtypesPathologic complete response (pCR)Residual cancer burden (RCB)Tumour-infiltrating lymphocytes (TILs)

trials

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ASCENTASCENT-03ASCENT-04 / KEYNOTE-D19ASCENT-05 / OptimICE-RD (AFT-65, GBG 119, NSABP B-63)BL-B01D1-307DESTINY-Breast04IMpassion130IMpassion131IZABRIGHT-Breast01KEYNOTE-355KEYNOTE-522OlympiAOptimICE-pCR (A012103)SCARLET (SWOG S2212)TROPION-Breast02TROPION-Breast03TROPION-Breast05WHEL (Women's Healthy Eating and Living)

pairings

8
ADC + checkpoint inhibitorCaution: cumulative anthracycline dose and the heartCaution: TOP1 ADC immediately after TOP1 ADCctDNA MRD → adjuvant therapy decisionGermline BRCA test → adjuvant PARP inhibitorHER2-low scoring → T-DXdPlatinum chemotherapy in HRD tumoursTROP2 PET → TROP2 ADC selection

roadmaps

3
ADC roadmap: from Mylotarg to bispecific and dual-payload ADCsTNBC roadmap: from 'nothing to target' to ADC + immunotherapy first lineTROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET

ideas

41
A billion-dollar prize for the first durable cure of a lethal metastatic cancerA bone drug to prevent breast cancer in BRCA1 carriersA national residual-disease weather service: serial blood tests for every curatively treated patient, pooledA permanent neutral non-profit sponsor for multi-company platform trialsA platform trial of very-low-cost metronomic chemotherapy in LMIC common cancersA ring-fenced metastasis programme with metastasis-specific endpointsADC for residual disease after KEYNOTE-522AI quantification of HER2-low and HER2-ultralowAlpha radioligands after ADC failureBlock the recycling that keeps dormant cells aliveCan MYC be drugged directly, and will patients tolerate it?Cancer interception vaccines for high-risk carriersConfirm or refute the harm of antioxidant supplements during chemotherapyctDNA-triggered escalation in early TNBCCure-focused prizes: pay for verified long-term cures, not for drugsDefault fertility preservation referral for every patient under 40 before treatmentDual-payload ADCs in first line to prevent resistanceEfflux-agnostic therapy for mesenchymal TNBCFertility preservation offered and funded by default before gonadotoxic treatmentFix the neutrophil count rule that excludes many people of African ancestryFlush dormant cells out of bone marrow, then kill themImplant a tiny device that tests twenty drugs inside the patient's own tumourIs aneuploidy itself a druggable vulnerability?Metastasis prevention as a formal indication with its own trials and regulatory pathwayNeoadjuvant ADC + IO replacing anthracycline chemotherapy in TNBCOff-the-shelf natural killer cells to sweep up residual diseaseOne-stop breast clinics: imaging, biopsy and a preliminary answer in a single visitOne-two punch: clear senescent cells after chemotherapyPatient-derived organoids to pick ADC payloadsPayload-class switching as the rule for ADC sequencingProspective arm-volume surveillance to catch and reverse lymphoedema earlyPublic country dashboards for the three WHO breast cancer targetsSequential multiple-assignment randomised trials to find the best order of ADCsSet each woman's mammogram interval from her last mammogram, using AI riskStarve MYC-driven tumours by blocking protein production machineryStop over-excluding people who could become pregnant; study pregnancy exposureStructured exercise prescribed like a drug in all curative-intent cancer careTIL-based omission of chemotherapy in stage I TNBCTROP2 PET to choose and sequence TROP2 ADCsTurn chromosomal chaos into a weakness with KIF18A inhibitorsWhat decides which disseminated cells ever colonise?

collections

1
Susan G. Komen

people

42
Alan AshworthAndrew TuttAngela DeMicheleAngelina JolieBinghe XuCarsten DenkertCharles E. Geyer Jr.Dawn L. HershmanDebu TripathyGiuseppe CuriglianoHatem SolimanHope S. RugoJennifer K. LittonJudy E. GarberLaura J. EssermanLeif W. EllisenLori J. PierceMariana Chavez-MacGregorMary-Claire KingMax S. WichaMiguel MartínMitchell D. SchnallPaolo VeronesiPriyanka SharmaRajendra BadweSabine LinnSara A. HurvitzSara López-TarruellaSara M. TolaneySeock-Ah ImShaoli SongSherene LoiSibylle LoiblSudeep GuptaSung-Bae KimSusan M. DomchekTakayuki UenoTimothy J. EberleinVincent K. TuohyXichun HuYi-Zhou JiangZhi-Ming Shao

bottlenecks

5
Incentives reward me-too drugs and marginal gainsInherited risk is mostly unidentifiedMetastasis is understood least and studied lastToo many combinations to testTrials do not represent the people who get cancer

key papers

6
ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancerDESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable groupKEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancerMASAI: AI-supported mammography screening finds more cancers with half the radiologist workloadOlympiA: a year of olaparib after surgery for BRCA-mutated, high-risk early breast cancerPROSE consortium: preventive surgery lowers cancer and death in BRCA1 and BRCA2 carriers

Key papers

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rctLancet Oncology 2023
MASAI: AI-supported mammography screening finds more cancers with half the radiologist workload

AI can take over one reader's work in double-reading screening programmes while finding more cancers. Whether the extra cancers found are ones that would have harmed women, and whether interval cancers fall, is the question the trial's primary endpoint will answer.

rctNew England Journal of Medicine 2022changed practice
DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group

Patients whose breast cancer was previously called HER2-negative may now be eligible for an effective HER2-directed drug if their tumour has even low-level HER2 staining, so pathology reports must now distinguish HER2-low (1+ or 2+/ISH-negative) from HER2-zero. This applies to metastatic disease after at least one line of chemotherapy; it does not mean these patients benefit from trastuzumab or other older HER2 drugs.

rctNew England Journal of Medicine 2022changed practice
KEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer

For stage II-III triple-negative breast cancer, chemotherapy plus pembrolizumab before surgery and pembrolizumab alone afterwards is now the standard approach worldwide, and the survival gain is real, not just a surrogate. It does not apply to stage I disease or to hormone-receptor-positive or HER2-positive cancers. The price is a year of immunotherapy with a meaningful chance of a permanent endocrine side effect such as hypothyroidism or adrenal insufficiency.

rctNew England Journal of Medicine 2021changed practice
ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer

Sacituzumab govitecan is a standard second-line or later treatment for metastatic triple-negative breast cancer, roughly doubling survival compared with the chemotherapies it was tested against. Patients should expect neutropenia and diarrhoea, which are manageable with growth factor support and loperamide. Trials are now testing it earlier, in first-line combinations with pembrolizumab and after surgery for residual disease.

rctNew England Journal of Medicine 2021changed practice
OlympiA: a year of olaparib after surgery for BRCA-mutated, high-risk early breast cancer

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.

observationalJAMA 2010changed practice
PROSE consortium: preventive surgery lowers cancer and death in BRCA1 and BRCA2 carriers

For women who carry a BRCA mutation, preventive removal of the ovaries and tubes saves lives, and preventive mastectomy almost eliminates breast cancer. These are the strongest prevention effects in oncology, which is why finding carriers before they develop cancer matters so much.

Latest papers

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Literature trend3,747 papers in the last 12 months+11% vs prior 12How this is computed
Latest papers · live from Europe PMC
Open in Europe PMC

Query for this cancer: (TITLE:"Triple-negative breast cancer" OR ABSTRACT:"Triple-negative breast cancer" OR TITLE:"TNBC" OR ABSTRACT:"TNBC") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Triple-negative breast cancer (TNBC), not a curated reading list.

Connected

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technologies

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Antibody-drug conjugate (ADC)Bispecific ADCCancer interception vaccinesChemoprevention & risk-reducing surgeryDietary supplements during cancer treatment: interactions and harmsDigital pathology & AIDual-payload ADCExercise & lifestyle oncologyExercise during chemotherapy and radiotherapyFAPI PETFasting and fasting-mimicking diets around chemotherapyGermline (hereditary) testingHistopathology & immunohistochemistryImmune checkpoint inhibitorsIntratumoural gene electrotransfer (IL-12 plasmid)Mammography & tomosynthesisMirai (MIT breast cancer risk from mammograms)MRD / molecular residual disease testingPARP inhibitorsPARP PETPersonalised neoantigen (mRNA) vaccinesPlatinum agentsRNA sequencing & expression profilingSentinel lymph node biopsyTROP2 PETUltrasound

targets

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Androgen receptorATRBRCA1 / BRCA2 (HRD)CD73 / adenosine axisEGFRFAPFolate receptor alphaHER2HER3LIV-1 (SLC39A6)Nectin-4PARPPD-1PD-L1ROR1TP53TROP2WEE1

drugs

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Phase 1Bispecific ADC
AK146D1
ApprovedMonoclonal antibody (anti-PD-L1)
Atezolizumab · Tecentriq / Tecentriq Hybreza (SC)
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
Not mapped hereAlkylating agent (oxazaphosphorine prodrug)
Cyclophosphamide · Cytoxan / Endoxan
ApprovedADC
Datopotamab deruxtecan · Datroway
ApprovedCytotoxic chemotherapy (anthracycline)
Doxorubicin · Adriamycin
ApprovedMonoclonal antibody (anti-PD-L1)
Durvalumab · Imfinzi
Not mapped hereSynthetic halichondrin B analogue (microtubule dynamics inhibitor)
Eribulin · Halaven
Phase 2Theranostic pair (peptide radioligand)
FAP-2286 (177Lu / 68Ga)
NegativeSmall molecule (claimed PARP inhibitor)
Iniparib
Under reviewBispecific antibody (PD-1×VEGF)
Ivonescimab
Phase 3Bispecific ADC
Izalontamab brengitecan
ApprovedSmall-molecule PARP inhibitor
Olaparib · Lynparza
ApprovedCytotoxic chemotherapy (taxane)
Paclitaxel / nab-paclitaxel · Taxol / Abraxane
Phase 3ADC
Patritumab deruxtecan
Not mapped hereProtease-activated fluorescent imaging agent
Pegulicianine · Lumisight
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
Phase 2ADC
Puxitatug samrotecan
ApprovedADC
Sacituzumab govitecan · Trodelvy
Under reviewADC
Sacituzumab tirumotecan
EstablishedTumour-informed ctDNA MRD test
Signatera
ApprovedSmall-molecule PARP inhibitor
Talazoparib · Talzenna
ApprovedADC
Trastuzumab deruxtecan · Enhertu

companies

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AstraZenecaBristol Myers SquibbCelldex TherapeuticsCircle PharmaDaiichi SankyoGilead Sciences (incl. Kite)LunitMerck & Co. (MSD)Mersana TherapeuticsSichuan Kelun-BiotechSystImmune / Sichuan Biokin

institutions

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Alliance for Clinical Trials in OncologyBreast Cancer Research FoundationBreast Cancer TrialsBreast International Group (BIG)Cleveland Clinic Taussig Cancer InstituteDana-Farber Brigham Cancer CenterFudan University Shanghai Cancer CenterGEICAM Spanish Breast Cancer GroupGerman Breast Group (GBG)Guy's and St Thomas' NHS Foundation Trust / King's Health Partners Cancer CentreHospital General Universitario Gregorio MarañónIEO – European Institute of OncologyIndiana University Melvin and Bren Simon Comprehensive Cancer CenterInstitut CurieInstitut Jules BordetInstitut Paoli-CalmettesKorle Bu Teaching HospitalLagos University Teaching HospitalMays Cancer Center at UT Health San AntonioNRG OncologySalk Institute Cancer CenterSkåne University Hospital / Lund University Cancer CentreSOLTI Cancer Research GroupSWOG Cancer Research NetworkThe University of Kansas Cancer CenterTianjin Medical University Cancer Institute and HospitalUNC Lineberger Comprehensive Cancer CenterUNICANCERUniversity of Malaya Medical CentreVanderbilt-Ingram Cancer Center

pathways

5
DNA damage response & homologous recombinationEpithelial–mesenchymal transition & drug effluxp53 / RB / cell-cycle checkpointPD-1 / PD-L1 immune checkpoint & T-cell activationPI3K / AKT / mTOR

terms

9
ADC sequencingCancer health disparities and equityCombined positive score (CPS)HER2-low and HER2-ultralowHomologous recombination deficiency (HRD)PAM50 / intrinsic subtypesPathologic complete response (pCR)Residual cancer burden (RCB)Tumour-infiltrating lymphocytes (TILs)

trials

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ASCENTASCENT-03ASCENT-04 / KEYNOTE-D19ASCENT-05 / OptimICE-RD (AFT-65, GBG 119, NSABP B-63)BL-B01D1-307DESTINY-Breast04IMpassion130IMpassion131IZABRIGHT-Breast01KEYNOTE-355KEYNOTE-522OlympiAOptimICE-pCR (A012103)SCARLET (SWOG S2212)TROPION-Breast02TROPION-Breast03TROPION-Breast05WHEL (Women's Healthy Eating and Living)

pairings

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ADC + checkpoint inhibitorCaution: cumulative anthracycline dose and the heartCaution: TOP1 ADC immediately after TOP1 ADCctDNA MRD → adjuvant therapy decisionGermline BRCA test → adjuvant PARP inhibitorHER2-low scoring → T-DXdPlatinum chemotherapy in HRD tumoursTROP2 PET → TROP2 ADC selection

roadmaps

3
ADC roadmap: from Mylotarg to bispecific and dual-payload ADCsTNBC roadmap: from 'nothing to target' to ADC + immunotherapy first lineTROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET

ideas

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A billion-dollar prize for the first durable cure of a lethal metastatic cancerA bone drug to prevent breast cancer in BRCA1 carriersA national residual-disease weather service: serial blood tests for every curatively treated patient, pooledA permanent neutral non-profit sponsor for multi-company platform trialsA platform trial of very-low-cost metronomic chemotherapy in LMIC common cancersA ring-fenced metastasis programme with metastasis-specific endpointsADC for residual disease after KEYNOTE-522AI quantification of HER2-low and HER2-ultralowAlpha radioligands after ADC failureBlock the recycling that keeps dormant cells aliveCan MYC be drugged directly, and will patients tolerate it?Cancer interception vaccines for high-risk carriersConfirm or refute the harm of antioxidant supplements during chemotherapyctDNA-triggered escalation in early TNBCCure-focused prizes: pay for verified long-term cures, not for drugsDefault fertility preservation referral for every patient under 40 before treatmentDual-payload ADCs in first line to prevent resistanceEfflux-agnostic therapy for mesenchymal TNBCFertility preservation offered and funded by default before gonadotoxic treatmentFix the neutrophil count rule that excludes many people of African ancestryFlush dormant cells out of bone marrow, then kill themImplant a tiny device that tests twenty drugs inside the patient's own tumourIs aneuploidy itself a druggable vulnerability?Metastasis prevention as a formal indication with its own trials and regulatory pathwayNeoadjuvant ADC + IO replacing anthracycline chemotherapy in TNBCOff-the-shelf natural killer cells to sweep up residual diseaseOne-stop breast clinics: imaging, biopsy and a preliminary answer in a single visitOne-two punch: clear senescent cells after chemotherapyPatient-derived organoids to pick ADC payloadsPayload-class switching as the rule for ADC sequencingProspective arm-volume surveillance to catch and reverse lymphoedema earlyPublic country dashboards for the three WHO breast cancer targetsSequential multiple-assignment randomised trials to find the best order of ADCsSet each woman's mammogram interval from her last mammogram, using AI riskStarve MYC-driven tumours by blocking protein production machineryStop over-excluding people who could become pregnant; study pregnancy exposureStructured exercise prescribed like a drug in all curative-intent cancer careTIL-based omission of chemotherapy in stage I TNBCTROP2 PET to choose and sequence TROP2 ADCsTurn chromosomal chaos into a weakness with KIF18A inhibitorsWhat decides which disseminated cells ever colonise?

collections

1
Susan G. Komen

people

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Alan AshworthAndrew TuttAngela DeMicheleAngelina JolieBinghe XuCarsten DenkertCharles E. Geyer Jr.Dawn L. HershmanDebu TripathyGiuseppe CuriglianoHatem SolimanHope S. RugoJennifer K. LittonJudy E. GarberLaura J. EssermanLeif W. EllisenLori J. PierceMariana Chavez-MacGregorMary-Claire KingMax S. WichaMiguel MartínMitchell D. SchnallPaolo VeronesiPriyanka SharmaRajendra BadweSabine LinnSara A. HurvitzSara López-TarruellaSara M. TolaneySeock-Ah ImShaoli SongSherene LoiSibylle LoiblSudeep GuptaSung-Bae KimSusan M. DomchekTakayuki UenoTimothy J. EberleinVincent K. TuohyXichun HuYi-Zhou JiangZhi-Ming Shao

bottlenecks

5
Incentives reward me-too drugs and marginal gainsInherited risk is mostly unidentifiedMetastasis is understood least and studied lastToo many combinations to testTrials do not represent the people who get cancer

key papers

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ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancerDESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable groupKEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancerMASAI: AI-supported mammography screening finds more cancers with half the radiologist workloadOlympiA: a year of olaparib after surgery for BRCA-mutated, high-risk early breast cancerPROSE consortium: preventive surgery lowers cancer and death in BRCA1 and BRCA2 carriers