Metastatic triple-negative breast cancer

aka Advanced triple-negative breast cancer, Stage IV TNBC, Recurrent triple-negative breast cancer

Triple-negative breast cancer that has spread is not curable, but its treatment has been transformed since 2020. By PD-L1 score, first treatment is pembrolizumab with chemotherapy or with sacituzumab govitecan, or datopotamab deruxtecan or sacituzumab govitecan alone; BRCA carriers can take a PARP inhibitor tablet; and trastuzumab deruxtecan reaches the third of tumours with low HER2.

Part ofTriple-negative breast cancer (TNBC)

Metastatic triple-negative disease spreads early to lung, liver and brain and grows fast, so the first line matters more than in other breast cancers. At relapse the tumour is retested, because receptors can change, and three results steer treatment: PD-L1 by combined positive score (10 or more in roughly four in ten patients), germline BRCA status and the HER2 immunohistochemistry score that identifies HER2-low disease. Until 2018 the options were taxanes, anthracyclines, platinum, capecitabine and eribulin, with platinum favoured in BRCA carriers after the TNT trial.

Immunotherapy came first. IMpassion130 showed atezolizumab with nab-paclitaxel delays progression in PD-L1-positive disease and won an accelerated approval that was withdrawn in 2021 when IMpassion131 with paclitaxel failed. KEYNOTE-355 (847 patients) showed pembrolizumab with chemotherapy extends survival in tumours with a combined positive score of 10 or more (hazard ratio 0.73) and became the first-line standard for that group. The TROP2 antibody-drug conjugates then moved into the first line: ASCENT-04 showed sacituzumab govitecan with pembrolizumab beats chemotherapy with pembrolizumab in PD-L1-positive disease, ASCENT-03 showed sacituzumab govitecan beats chemotherapy in PD-L1-negative disease, and TROPION-Breast02 (644 patients) showed datopotamab deruxtecan extends overall survival from 18.7 to 23.7 months in patients who cannot have immunotherapy, the first first-line antibody-drug conjugate to do so; all three were approved in 2026.

Later lines were transformed earlier. ASCENT (529 patients with at least two prior lines) showed sacituzumab govitecan nearly doubles survival against chemotherapy (12.1 against 6.7 months, hazard ratio 0.48), the first antibody-drug conjugate approval in triple-negative disease in 2020. For germline BRCA carriers OlympiAD (302 patients) and EMBRACA (431) showed olaparib and talazoparib extend progression-free survival over chemotherapy (7.0 against 4.2 months, hazard ratio 0.58; 8.6 against 5.6 months, hazard ratio 0.54) without a significant survival gain. DESTINY-Breast04 included a small HER2-low triple-negative cohort that pointed the same way as the main result, and trastuzumab deruxtecan is an option for the third of tumours that are HER2-low; the bispecific antibody-drug conjugate izalontamab brengitecan posted a positive phase 3 in 2026. Whether a second topoisomerase-payload conjugate works after the first, how to select patients for TROP2 drugs, and what to do about brain metastases, present in up to a third to nearly half of patients, are the open questions.

State of the art

Antibody-drug conjugates are first-line therapy for every PD-L1 group, alone or with pembrolizumab.
PARP inhibitors give BRCA carriers a chemotherapy-free option.
A bispecific antibody-drug conjugate has succeeded in phase 3.

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.

Median survival in first-line trials approaches two years, roughly double the chemotherapy era.

Red cards

From the labels and guidelines behind the standard of care. Your team's thresholds win.

Emergency services now
Bleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
Capecitabine Carboplatin Eribulin Gemcitabine Paclitaxel / nab-paclitaxel source
Emergency services now
Skin reaction
Blisters, peeling, or sores in the mouth or eyes with a rash. Enfortumab vedotin carries a boxed warning for Stevens-Johnson syndrome and toxic epidermal necrolysis, mostly in the first cycle.
Datopotamab deruxtecan Izalontamab brengitecan Sacituzumab govitecan Trastuzumab deruxtecan source
Emergency services now
Blood clot
A swollen painful calf, or sudden breathlessness with chest pain; venous thromboembolism including pulmonary embolism is a labelled warning.
Olaparib Talazoparib source
Emergency services now
Blood clot (lenalidomide, pomalidomide, thalidomide)
A swollen painful calf, or sudden breathlessness with chest pain; venous and arterial thromboembolism is a boxed warning and blood-thinning prophylaxis is recommended.
Capecitabine source
Emergency services now
Hypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Pembrolizumab source
Call the 24-hour line now
Interstitial lung disease or pneumonitis
Any new or worsening cough, breathlessness or fever. The label says to interrupt treatment for any suspected ILD and to permanently discontinue for grade 2 or higher.
Datopotamab deruxtecan Trastuzumab deruxtecan source

See all on the product pages:Capecitabine Carboplatin Datopotamab deruxtecan Eribulin Gemcitabine Izalontamab brengitecan Olaparib Paclitaxel / nab-paclitaxel Pembrolizumab Sacituzumab govitecan Talazoparib Trastuzumab deruxtecan·Printable cards in the navigator

Anatomy and lymph node drainage

Breast: subsites and node stations · wireframe schematic, not to scale

Organ atlas →

Most cancers start in the ducts and drain first to the axillary nodes, which is why the armpit is checked and a sentinel node is sampled.

Subsites

Ducts (most cancers start here)PD-L1-positive basal-like disease (combined positive score 10 or more; pembrolizumab combinations) · HER2-low triple-negative disease (trastuzumab deruxtecan)
Lobules (lobular carcinoma; phyllodes tumours arise from the surrounding stroma)
Upper outer quadrant (commonest site)
Nipple-areola

Regional lymph nodes

axillary level I
axillary level II-III
internal mammary
supraclavicular

Same organ: Triple-negative breast cancer (TNBC), Breast cancer (all types), HR-positive / HER2-negative breast cancer, HER2-positive breast cancer, Male breast cancer, Ductal carcinoma in situ (DCIS), High-risk early HR-positive breast cancer, HR-positive metastatic breast cancer after CDK4/6 inhibitors, HER2-low and HER2-ultralow metastatic breast cancer, Early HER2-positive breast cancer, HER2-positive breast cancer with brain metastases, Early triple-negative breast cancer, Inflammatory breast cancer, Paget disease of the nipple, Phyllodes tumour of the breast

Who gets it and what has changed

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.

Many women with early triple-negative disease relapse, most within three years, joining those diagnosed with spread from the outset; median survival was about a year to eighteen months on chemotherapy alone and now approaches two years in first-line trials.

Group

breast

Cases by country

Cases by country · GLOBOCAN 2022

All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Lines of therapy by subgroup →Staging and risk scores →

Decisions you may face

4 with more than one option · full decision page →

One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.

First line, combined positive score 10 or more2 First line, PD-L1-negative or immunotherapy-ineligible4 Germline BRCA carriers3 Second line and beyond6 Brain metastases

First line, combined positive score 10 or more

Pembrolizumab with chemotherapy (KEYNOTE-355) or with sacituzumab govitecan (ASCENT-04).

PembrolizumabKEYNOTE-355Sacituzumab govitecanASCENT-04 / KEYNOTE-D19 Combined positive score (CPS)

First line, PD-L1-negative or immunotherapy-ineligible

Datopotamab deruxtecan (TROPION-Breast02) or sacituzumab govitecan (ASCENT-03); a taxane or platinum where antibody-drug conjugates are unavailable.

Datopotamab deruxtecanTROPION-Breast02Sacituzumab govitecanASCENT-03Paclitaxel / nab-paclitaxelCarboplatin

Germline BRCA carriers

Olaparib (OlympiAD) or talazoparib (EMBRACA) after or instead of first-line chemotherapy; platinum chemotherapy is also more active.

OlaparibOlympiADTalazoparibEMBRACACarboplatinGermline BRCA mutation (gBRCA)

Second line and beyond

Whichever TROP2 antibody-drug conjugate has not been used (ASCENT); trastuzumab deruxtecan for HER2-low tumours (DESTINY-Breast04); izalontamab brengitecan where available; eribulin, capecitabine or gemcitabine with carboplatin.

Sacituzumab govitecanASCENTTrastuzumab deruxtecanDESTINY-Breast04Izalontamab brengitecanEribulinCapecitabineGemcitabine

Brain metastases

Stereotactic radiosurgery or whole-brain radiotherapy with continued systemic therapy; antibody-drug conjugates have early evidence of intracranial activity.

Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)Brain metastases (intracranial disease)

Subtypes & biomarkers

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Subtypes

PD-L1-positive basal-like disease (combined positive score 10 or more; pembrolizumab combinations)
PD-L1-negative or immunotherapy-ineligible disease (antibody-drug conjugate first)
Germline BRCA-mutant metastatic triple-negative disease (olaparib, talazoparib, platinum)
HER2-low triple-negative disease (trastuzumab deruxtecan)
Early relapse within twelve months of curative chemotherapy (excluded from many first-line trials)
Triple-negative disease with brain metastases

Biomarkers clinicians test

PD-L1 by 22C3 combined positive score (10 or more for pembrolizumab)
Germline BRCA1 and BRCA2 (PARP inhibitors)
HER2 immunohistochemistry to identify HER2-low disease
Repeat receptor testing on a metastatic biopsy (receptor conversion)
TROP2 expression (not required for TROP2 antibody-drug conjugates)
Tumour mutational burden and microsatellite instability (tumour-agnostic immunotherapy)

How often this target appears

History

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2014TNT: carboplatin beats docetaxel in germline BRCA carriers
Carboplatin
2017OlympiAD: olaparib beats chemotherapy in germline BRCA disease
OlympiADOlaparib
2018EMBRACA and IMpassion130
EMBRACATalazoparibIMpassion130Atezolizumab
2020ASCENT and KEYNOTE-355
ASCENTSacituzumab govitecanKEYNOTE-355Pembrolizumab
2021IMpassion131 fails and atezolizumab is withdrawn in breast cancer
IMpassion131
2022DESTINY-Breast04 includes HER2-low triple-negative tumours
DESTINY-Breast04Trastuzumab deruxtecan
2025ASCENT-03, ASCENT-04 and TROPION-Breast02 positive in the first line
ASCENT-03 ASCENT-04 / KEYNOTE-D19 TROPION-Breast02
2026First-line antibody-drug conjugate approvals; izalontamab brengitecan phase 3 positive
Datopotamab deruxtecanSacituzumab govitecanBL-B01D1-307

What changed

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Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.

All 20 changes by month →

FollowWatch this cancer and Saved shows what changed since you last looked.Follow by feed

In development

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What is in development for Metastatic triple-negative breast cancer, drawn from the whole corpus: 18 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.

Drugs in phase 3 · 2

Phase 3Bispecific ADC

Izalontamab brengitecan

Phase 3ADC

Patritumab deruxtecan

Technologies being tested · 3

TROP2 PET Dual-payload ADC Bispecific ADC

Trials under way · 2

TROPION-Breast05 · phase 3 · AstraZeneca / Daiichi Sankyo
IZABRIGHT-Breast01 · phase 2/3 · BMS

Trials reported · 11

BL-B01D1-307 · phase 3 · 2026 · positive
ASCENT · phase 3 · 2020 · positive
ASCENT-03 · phase 3 · 2025 · positive
ASCENT-04 / KEYNOTE-D19 · phase 3 · 2025 · positive
DESTINY-Breast04 · phase 3 · 2022 · positive
EMBRACA · phase 3 · 2018 · positive
IMpassion130 · phase 3 · 2018 · mixed
IMpassion131 · phase 3 · 2020 · negative
KEYNOTE-355 · phase 3 · 2020 · positive
OlympiAD · phase 3 · 2017 · positive
TROPION-Breast02 · phase 3 · 2025 · positive

Open problems and what is being done

Cross-resistance between antibody-drug conjugates sharing a topoisomerase I payload.
What is being done about this
Resistance to treatment
and how the field plans to fix it →
Available now
TalazoparibApproved
In trials
Dual-payload ADCPhase 1
Ideas and roadmaps
Nothing recorded yet.
Also on OnCo: Resistance atlas · Lines of therapy.
No biomarker selects patients for TROP2 drugs.
Brain metastases remain undertreated and are excluded from most trials.
What is being done about this
Advanced and metastatic disease
and how the field plans to fix it →
Available now
Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)Established
Trastuzumab deruxtecanApproved
In trials
KEYNOTE-355Positive
Ideas and roadmaps
Nothing recorded yet.
Also on OnCo: Atlas of advanced disease · Invasion and metastasis.
Access: the new first-line drugs cost many times more than chemotherapy.

Trials

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Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

Metastatic triple-negative breast cancer

condition: Metastatic triple-negative breast cancer

Open on ClinicalTrials.gov →

within

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Landmark trials

ASCENT ASCENT-03 ASCENT-04 / KEYNOTE-D19 BL-B01D1-307 DESTINY-Breast04 EMBRACA IMpassion130 IMpassion131 IZABRIGHT-Breast01 KEYNOTE-355 OlympiAD TROPION-Breast02 TROPION-Breast05

Expert centres

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Where the expertise is

Expert centres

51 centres in 17 countries · 0 with a trial for this cancer on record · second-opinion finder →

Choose a region from the globe in the header to mark centres near you.

51 centres


MD Anderson Cancer Center Houston · cancer center	United States	NCI comprehensive	6,724	95,007	CAR-NK & CAR-macrophage Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +2	#2
Samsung Medical Center Seoul · hospital	South Korea	none recorded	1,312	17,172	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#3
Mayo Clinic Rochester, MN · hospital	United States	NCI comprehensive	4,511	44,748	Carbon-ion therapy Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#5
Gustave Roussy Villejuif · cancer center Programme: Breast ADC trials	France	none recorded	1,855	31,182	ZAP-X gyroscopic radiosurgery Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#6
The Royal Marsden London · cancer center Programme: Breast cancer	United Kingdom	none recorded	1,026	17,745	MR-guided adaptive radiotherapy PARP inhibitors	#7
Seoul National University Hospital Seoul · hospital	South Korea	none recorded	1,607	24,676	Gamma Knife Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#8
Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center Baltimore · cancer center	United States	NCI comprehensive	2,955	41,449	Multi-cancer early detection (MCED)Liquid biopsy (ctDNA)Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems +2	#10
Charité Universitätsmedizin Berlin Berlin · university	Germany	none recorded	1,563	17,749	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems CyberKnife robotic radiosurgery Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#12
National Cancer Center Hospital Tokyo · government	Japan	none recorded	1,599	21,937	none recorded	#13
Massachusetts General Hospital Cancer Center Boston · hospital	United States	NCI comprehensive	3,582	54,857	Proton therapy Small-molecule kinase inhibitors Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#16
Cleveland Clinic Taussig Cancer Institute Cleveland · hospital	United States	NCI comprehensive	2,264	29,412	Off-the-shelf cancer vaccines Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#20
Severance Hospital, Yonsei University Seoul · hospital	South Korea	none recorded	464	3,248	Carbon-ion therapy Robotic & minimally invasive surgery Carbon-ion synchrotrons and facilities Gamma Knife +1	#22
Stanford Health Care / Stanford Cancer Institute Stanford · university	United States	NCI comprehensive	3,000	50,162	CAR-T cell therapy SBRT / SABR (stereotactic radiotherapy)CyberKnife robotic radiosurgery Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)+1	#30
UCSF Helen Diller Family Comprehensive Cancer Center San Francisco · cancer center	United States	NCI comprehensive	2,800	46,704	PSMA PET Gamma Knife Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#33
Karolinska University Hospital Stockholm · university	Sweden	none recorded	987	12,440	Gamma Knife Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#39

(showing the first 15)

These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Metastatic triple-negative breast cancer but is thinly recorded here will look small.

Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.

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. The second-opinion finder explains how referral works in your country.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Metastatic triple-negative breast cancer

Generated from this cancer's standard of care, biomarkers, and pipeline · 22 questions

Newly diagnosed

What is my exact diagnosis, stage, and grade, and which tests established them?
Why: Everything else follows from an accurate stage and subtype.
Which biomarkers have been tested on my tumour (for example PD-L1 by 22C3 combined positive score, Germline BRCA1 and BRCA2, HER2 immunohistochemistry to identify HER2-low disease, Repeat receptor testing on a metastatic biopsy, TROP2 expression), and what were the results?
Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
Which subtype is my cancer, and does that change the recommended treatment?
Why: Recognised subtypes for this cancer include PD-L1-positive basal-like disease, PD-L1-negative or immunotherapy-ineligible disease, Germline BRCA-mutant metastatic triple-negative disease.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.

First line, combined positive score 10 or more

For my situation (first line, combined positive score 10 or more), which of the standard options do you recommend and why?
Why: Guideline options include: Pembrolizumab with chemotherapy (KEYNOTE-355) or with sacituzumab govitecan (ASCENT-04).
Am I a candidate for Pembrolizumab, Sacituzumab govitecan, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of KEYNOTE-355 and ASCENT-04 / KEYNOTE-D19 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

First line, PD-L1-negative or immunotherapy-ineligible

For my situation (first line, pd-l1-negative or immunotherapy-ineligible), which of the standard options do you recommend and why?
Why: Guideline options include: Datopotamab deruxtecan (TROPION-Breast02) or sacituzumab govitecan (ASCENT-03); a taxane or platinum where antibody-drug conjugates are unavailable.
Am I a candidate for Datopotamab deruxtecan, Sacituzumab govitecan, Paclitaxel / nab-paclitaxel or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of TROPION-Breast02 and ASCENT-03 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Germline BRCA carriers

For my situation (germline brca carriers), which of the standard options do you recommend and why?
Why: Guideline options include: Olaparib (OlympiAD) or talazoparib (EMBRACA) after or instead of first-line chemotherapy; platinum chemotherapy is also more active.
Am I a candidate for Olaparib, Talazoparib, Carboplatin, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of OlympiAD and EMBRACA apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Second line and beyond

For my situation (second line and beyond), which of the standard options do you recommend and why?
Why: Guideline options include: Whichever TROP2 antibody-drug conjugate has not been used (ASCENT); trastuzumab deruxtecan for HER2-low tumours (DESTINY-Breast04); izalontamab brengitecan where available; eribulin, capecitabine or gemcitabine with carboplatin.
Am I a candidate for Sacituzumab govitecan, Trastuzumab deruxtecan, Izalontamab brengitecan or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of ASCENT and DESTINY-Breast04 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Brain metastases

For my situation (brain metastases), which of the standard options do you recommend and why?
Why: Guideline options include: Stereotactic radiosurgery or whole-brain radiotherapy with continued systemic therapy; antibody-drug conjugates have early evidence of intracranial activity.

Any stage

Are there clinical trials I could join, for example of Izalontamab brengitecan, BL-B01D1-307, Sacituzumab tirumotecan, TROPION-Breast05?
Why: Trials are how the next standard of care is set; asking early keeps options open.
Would a second opinion at a high-volume centre change anything, and can you help arrange it?
Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
Why: Supportive care improves quality of life and helps patients complete treatment.
I read that “Cross-resistance between antibody-drug conjugates sharing a topoisomerase I payload”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “No biomarker selects patients for TROP2 drugs”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.