OnCo
cancersCancer

HER2-positive breast cancer

HER2-positive breast cancer was once the most aggressive subtype and is now one of the most treatable, thanks to trastuzumab and, more recently, Enhertu.

HER2-positive breast cancer (15-20% of cases; HER2 IHC 3+ or ISH-amplified) was the most aggressive subtype until trastuzumab (1998) made it one of the most treatable. The modern curative pathway is response-adapted: neoadjuvant chemotherapy with dual HER2 blockade (or, since 2026, T-DXd followed by THP), surgery, then either antibody completion for patients with a pathologic complete response or an ADC for residual disease (T-DM1 from KATHERINE, now T-DXd from DESTINY-Breast05). Small node-negative tumours are cured with paclitaxel-trastuzumab alone; PHERGain showed that an early PET response can spare a third of patients chemotherapy altogether. Extended adjuvant neratinib and adjuvant pertuzumab add small gains in higher-risk, node-positive disease.

Metastatic disease has been transformed twice: by CLEOPATRA's pertuzumab (OS 57 months) and then by trastuzumab deruxtecan, which beat T-DM1 by a wide margin in second line (DESTINY-Breast03) and beat THP in first line (DESTINY-Breast09, PFS 40.7 months; approved 2025). Brain metastases, which develop in up to half of patients, are now treatable systemically with tucatinib (HER2CLIMB) and T-DXd (DESTINY-Breast12). HER2CLIMB-05 (tucatinib maintenance) and PATINA (palbociclib maintenance in HR+/HER2+, approved 2026) intensify chemotherapy-free maintenance, and a wave of Chinese HER2 ADCs (trastuzumab rezetecan, BL-M07D1, ARX788, disitamab vedotin) is producing Enhertu-scale results.

Open problems are the sequencing of HER2 ADCs after T-DXd (payload cross-resistance), interstitial lung disease, cardiotoxicity across years of therapy, the cost and duration of antibody therapy, brain metastases prevention, and de-escalation: identifying the substantial fraction of patients who are over-treated. The pipeline is defined by T-DXd's move into every curative setting, tucatinib-based maintenance, next-generation and biparatopic HER2 ADCs (zanidatamab zovodotin), HER2 CAR-T and vaccines, and imaging- and ctDNA-adapted de-escalation trials.

State of the art today

  • T-DXd across the disease continuum.
  • Chemotherapy de-escalation guided by early response.
  • Response-adapted curative therapy: pCR patients de-escalate, residual disease escalates to an ADC (now T-DXd, iDFS HR 0.47 vs T-DM1).
  • T-DXd across the continuum: neoadjuvant (2026), post-neoadjuvant (2026), first-line metastatic with pertuzumab (2025, PFS 40.7 months), second line, and brain metastases.
  • Systemic control of brain metastases (tucatinib, T-DXd) allowing deferral of radiation.
  • Chemotherapy-free maintenance intensification: tucatinib (HER2CLIMB-05) and palbociclib for HR+/HER2+ (PATINA).
  • Chemotherapy omission for a third of patients using early PET response (PHERGain).
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.

  • Ten-year survival above 80% for early disease, from a subtype that was the deadliest in the 1990s.
Who it affects

15-20% of breast cancers (roughly 400,000 cases per year worldwide).

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.

  • Ten-year survival for early-stage disease treated with trastuzumab-based therapy exceeds 80%.
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. HER2+ disease is roughly 15-20% of cases; the figures shown are for all breast cancer.

Standard of care

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Early stage

Neoadjuvant THP or T-DXd → surgery → trastuzumab/pertuzumab (pCR) or T-DXd/T-DM1 (residual).

NCCN · Category 1, preferred: neoadjuvant pertuzum…ESMO-MCBS · A (KATHERINE); A (HERA); C (NeoSphere, APHI…
TrastuzumabTrastuzumab deruxtecanTrastuzumab emtansineDESTINY-Breast11
Metastatic

T-DXd + pertuzumab first line (DESTINY-Breast09); tucatinib + trastuzumab + capecitabine for brain metastases; palbociclib maintenance if HR+.

ESMO-MCBS · 4 (DESTINY-Breast03); 4 (CLEOPATRA); 4 (HER…
DESTINY-Breast09TucatinibPalbociclib
Stage I (≤2-3 cm, node-negative)

Surgery then weekly paclitaxel × 12 + trastuzumab × 1 year (APT); T-DM1 × 17 cycles is an alternative (ATEMPT). Endocrine therapy if HR+.

NCCN · 2A
APT (adjuvant paclitaxel-trastuzumab)Paclitaxel / nab-paclitaxelTrastuzumabTrastuzumab emtansine
Stage II-III, neoadjuvant

TCHP (docetaxel, carboplatin, trastuzumab, pertuzumab) or anthracycline-taxane + HP; from 2026, T-DXd × 4 → THP (DESTINY-Breast11, pCR 67%). PET-adapted chemotherapy omission (PHERGain) in trials.

NCCN · 1
DESTINY-Breast11Trastuzumab deruxtecanPertuzumabPHERGain
Post-neoadjuvant, pathologic complete response

Complete 1 year of trastuzumab (± pertuzumab if node-positive at diagnosis); endocrine therapy if HR+; radiation per stage.

NCCN · 1
TrastuzumabPertuzumabAPHINITYHERA, NSABP B-31 & NCCTG N9831 (adjuvant trastuzumab)
Post-neoadjuvant, residual invasive disease

T-DXd (DESTINY-Breast05, iDFS HR 0.47 vs T-DM1; approved 2026) replacing T-DM1 (KATHERINE); consider extended adjuvant neratinib for HR+ high-risk.

NCCN · 1 (T-DM1); T-DXd pending update
DESTINY-Breast05KATHERINETrastuzumab deruxtecanTrastuzumab emtansineNeratinib
Adjuvant (upfront surgery), node-positive

Chemotherapy + trastuzumab + pertuzumab for 1 year (APHINITY); trastuzumab alone for lower risk; 6 months acceptable where resources are limited (PERSEPHONE).

NCCN · 1
APHINITYPERSEPHONEPertuzumabTrastuzumab
Metastatic, first line

T-DXd + pertuzumab (DESTINY-Breast09, PFS 40.7 months; approved 2025) or taxane + trastuzumab + pertuzumab (CLEOPATRA) followed by maintenance: HP ± tucatinib (HER2CLIMB-05) and, if HR+, endocrine therapy + palbociclib (PATINA, approved 2026).

NCCN · 1, preferred (T-DXd + pertuzumab)ESMO-MCBS · 4 (CLEOPATRA)
DESTINY-Breast09CLEOPATRAHER2CLIMB-05Trastuzumab deruxtecanPertuzumabTucatinibPalbociclib
Metastatic, second line

T-DXd if not used first line (DESTINY-Breast03, PFS HR 0.33 vs T-DM1); tucatinib + trastuzumab + capecitabine, especially with brain metastases (HER2CLIMB).

NCCN · 1ESMO-MCBS · 4 (DESTINY-Breast03)
DESTINY-Breast03HER2CLIMBTrastuzumab deruxtecanTucatinib
Metastatic, later lines

T-DM1; neratinib or lapatinib + capecitabine; margetuximab + chemotherapy; trastuzumab + chemotherapy (continued HER2 blockade); zanidatamab and Chinese ADCs (trastuzumab rezetecan, disitamab vedotin) where available; trials.

NCCN · 2A
Trastuzumab emtansineNeratinibLapatinibMargetuximabZanidatamabTrastuzumab rezetecanDisitamab vedotin
Brain metastases

Systemic: tucatinib triplet or T-DXd (DESTINY-Breast12, intracranial ORR 72%); local: stereotactic radiosurgery or surgery for symptomatic or large lesions; whole-brain RT reserved.

NCCN · 1 (tucatinib triplet)
HER2CLIMBDESTINY-Breast12TucatinibTrastuzumab deruxtecanSBRT / SABR (stereotactic radiotherapy)
Cardiac monitoring and survivorship

LVEF every 3 months during anti-HER2 therapy; hold and cardioprotect for declines; anthracycline-free regimens preferred; long-term surveillance for late recurrence in HR+/HER2+.

Cardio-oncologyPERSEPHONE

Subtypes & biomarkers

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Subtypes
  • HER2-enriched (PAM50; highest pCR rates to HER2 blockade)
  • HR+/HER2+ ('triple-positive', ~50% of HER2+; lower pCR, endocrine therapy and CDK4/6 maintenance relevant)
  • HR-/HER2+ (higher pCR, more relapse in first 3 years)
  • HER2-mutant (activating mutations without amplification; T-DXd tumour-agnostic, HER2 TKIs; more common in lobular and HER2-low)
  • HER2 heterogeneous tumours (mixed amplified and non-amplified clones; lower pCR)
  • Small node-negative (stage I) disease cured by de-escalated therapy
Biomarkers clinicians test

Target prevalence in this cancer

Target / alterationPrevalenceSource
HER2
100%
Nature

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. 1987Slamon links HER2 amplification to poor prognosis
  2. 1987Slamon links HER2 amplification to poor prognosis

    Science paper identifying HER2/neu amplification in 25-30% of breast cancers.

    HER2
  3. 1998Trastuzumab approved
    Trastuzumab
  4. 1998Trastuzumab approved for metastatic disease

    First antibody for a solid tumour; OS benefit with chemotherapy.

    Trastuzumab
  5. 2005Adjuvant trastuzumab halves recurrence (HERA, B-31/N9831)
    HERA, NSABP B-31 & NCCTG N9831 (adjuvant trastuzumab)
  6. 2007Lapatinib: first HER2 pill
    Lapatinib
  7. 2012Pertuzumab and dual blockade (CLEOPATRA)
    PertuzumabCLEOPATRA
  8. 2013First solid-tumour ADC: T-DM1
    Trastuzumab emtansine
  9. 2013T-DM1: first solid-tumour ADC; pertuzumab first pCR-based approval
    Trastuzumab emtansinePertuzumab
  10. 2015APT: de-escalation for small tumours
    APT (adjuvant paclitaxel-trastuzumab)
  11. 2017First trastuzumab biosimilar; neratinib; APHINITY
    Trastuzumab biosimilarsNeratinibAPHINITY
  12. 2018KATHERINE: T-DM1 for residual disease
    KATHERINE
  13. 2019T-DXd approved; HER2CLIMB proves CNS benefit
    Trastuzumab deruxtecanHER2CLIMB
  14. 2020Tucatinib, margetuximab, Phesgo approved
    TucatinibMargetuximabPertuzumab
  15. 2021T-DXd beats T-DM1 (DESTINY-Breast03)
    DESTINY-Breast03
  16. 2021DESTINY-Breast03: T-DXd beats T-DM1
    DESTINY-Breast03
  17. 2024PHERGain chemotherapy omission; DESTINY-Breast12 brain metastases; zanidatamab approved (BTC)
    PHERGainDESTINY-Breast12Zanidatamab
  18. 2025DESTINY-Breast09 first-line approval; DESTINY-Breast05 and HER2CLIMB-05 positive; trastuzumab rezetecan approved (China, NSCLC)
    DESTINY-Breast09DESTINY-Breast05HER2CLIMB-05Trastuzumab rezetecan
  19. 2026T-DXd approved in early-stage disease
    DESTINY-Breast11
  20. 2026T-DXd approved neoadjuvant and post-neoadjuvant; palbociclib maintenance for HR+/HER2+ (PATINA)
    DESTINY-Breast11DESTINY-Breast05Palbociclib

Pipeline

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ApprovedBiparatopic bispecific antibody (HER2)
Zanidatamab · Ziihera
Not filedADC
Disitamab vedotin
Not mapped hereADC
Trastuzumab rezetecan
Phase 3ADC
Trastuzumab brengitecan
Phase 3ADC
ARX788
ApprovedSmall-molecule PI3Kα inhibitor and degrader
Inavolisib · Itovebi
HER2 PETHER2CLIMB-05HORIZON-Breast01PHERGainCan T-DXd alone cure early HER2-positive disease?Systemic-first management of HER2-positive brain metastasesSequencing HER2 ADCs by payload after T-DXdMRD / molecular residual disease testing

Open problems

  • Brain metastases in ~50% of metastatic patients.
  • Which patients can skip chemotherapy entirely.
  • Sequencing after T-DXd: no randomised data on which HER2 ADC or TKI works after TOP1-payload failure.
  • Interstitial lung disease with T-DXd in curative settings, where patients would otherwise be cured.
  • Over-treatment: which patients need pertuzumab, a full year of antibodies, or any chemotherapy at all (PHERGain-2, response-adapted trials).
  • Brain metastasis prevention and whether systemic-first strategies preserve cognition.
  • HR+/HER2+ ('triple-positive') disease: optimal integration of endocrine therapy, CDK4/6 inhibitors, and HER2 blockade.
  • Cardiotoxicity surveillance burden versus event rates in low-risk patients.
  • Global access: biosimilars have widened trastuzumab access but pertuzumab, T-DM1, and T-DXd remain unavailable in much of the world.
  • HER2 heterogeneity and HER2 conversion at relapse require re-biopsy strategies or HER2 PET.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
HER2-positive breast cancer
condition: HER2 positive breast cancer
Open on ClinicalTrials.gov →

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Landmark trials in OnCo

ACE-Breast-02APHINITYAPT (adjuvant paclitaxel-trastuzumab)BWEL (Breast Cancer Weight Loss, Alliance A011401)CLEOPATRADESTINY-Breast03DESTINY-Breast05DESTINY-Breast09DESTINY-Breast11DESTINY-Breast12HER2CLIMBHER2CLIMB-02HER2CLIMB-05HERA, NSABP B-31 & NCCTG N9831 (adjuvant trastuzumab)HORIZON-Breast01KATHERINEPERSEPHONEPHERGain

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 HER2-positive breast cancer

Generated from this cancer's standard of care, biomarkers, and pipeline · 43 questions

Newly diagnosed

  1. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  2. Which biomarkers have been tested on my tumour (for example HER2 IHC 3+ or ISH-amplified, HR status, pCR after neoadjuvant therapy, HER2 IHC 3+ or IHC 2+ with ISH amplification; HER2 heterogeneity, HR status), and what were the results?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  3. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include HER2-enriched, HR+/HER2+, HR-/HER2+.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Early stage

  1. For my situation (early stage), which of the standard options do you recommend and why?
    Why: Guideline options include: Neoadjuvant THP or T-DXd → surgery → trastuzumab/pertuzumab (pCR) or T-DXd/T-DM1 (residual).
  2. Am I a candidate for Trastuzumab, Trastuzumab deruxtecan, Trastuzumab emtansine, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of DESTINY-Breast11 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic

  1. For my situation (metastatic), which of the standard options do you recommend and why?
    Why: Guideline options include: T-DXd + pertuzumab first line (DESTINY-Breast09); tucatinib + trastuzumab + capecitabine for brain metastases; palbociclib maintenance if HR+.
  2. Am I a candidate for Tucatinib, Palbociclib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of DESTINY-Breast09 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Stage I (≤2-3 cm, node-negative)

  1. For my situation (stage i (≤2-3 cm, node-negative)), which of the standard options do you recommend and why?
    Why: Guideline options include: Surgery then weekly paclitaxel × 12 + trastuzumab × 1 year (APT); T-DM1 × 17 cycles is an alternative (ATEMPT). Endocrine therapy if HR+.
  2. Am I a candidate for Paclitaxel / nab-paclitaxel, Trastuzumab, Trastuzumab emtansine, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of APT (adjuvant paclitaxel-trastuzumab) apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Stage II-III, neoadjuvant

  1. For my situation (stage ii-iii, neoadjuvant), which of the standard options do you recommend and why?
    Why: Guideline options include: TCHP (docetaxel, carboplatin, trastuzumab, pertuzumab) or anthracycline-taxane + HP; from 2026, T-DXd × 4 → THP (DESTINY-Breast11, pCR 67%). PET-adapted chemotherapy omission (PHERGain) in trials.
  2. Am I a candidate for Trastuzumab deruxtecan, Pertuzumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of DESTINY-Breast11 and PHERGain apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Post-neoadjuvant, pathologic complete response

  1. For my situation (post-neoadjuvant, pathologic complete response), which of the standard options do you recommend and why?
    Why: Guideline options include: Complete 1 year of trastuzumab (± pertuzumab if node-positive at diagnosis); endocrine therapy if HR+; radiation per stage.
  2. Am I a candidate for Trastuzumab, Pertuzumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of APHINITY and HERA, NSABP B-31 & NCCTG N9831 (adjuvant trastuzumab) apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Post-neoadjuvant, residual invasive disease

  1. For my situation (post-neoadjuvant, residual invasive disease), which of the standard options do you recommend and why?
    Why: Guideline options include: T-DXd (DESTINY-Breast05, iDFS HR 0.47 vs T-DM1; approved 2026) replacing T-DM1 (KATHERINE); consider extended adjuvant neratinib for HR+ high-risk.
  2. Am I a candidate for Trastuzumab deruxtecan, Trastuzumab emtansine, Neratinib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of DESTINY-Breast05 and KATHERINE apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Adjuvant (upfront surgery), node-positive

  1. For my situation (adjuvant (upfront surgery), node-positive), which of the standard options do you recommend and why?
    Why: Guideline options include: Chemotherapy + trastuzumab + pertuzumab for 1 year (APHINITY); trastuzumab alone for lower risk; 6 months acceptable where resources are limited (PERSEPHONE).
  2. Am I a candidate for Pertuzumab, Trastuzumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of APHINITY and PERSEPHONE apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, first line

  1. For my situation (metastatic, first line), which of the standard options do you recommend and why?
    Why: Guideline options include: T-DXd + pertuzumab (DESTINY-Breast09, PFS 40.7 months; approved 2025) or taxane + trastuzumab + pertuzumab (CLEOPATRA) followed by maintenance: HP ± tucatinib (HER2CLIMB-05) and, if HR+, endocrine therapy + palbociclib (PATINA, approved 2026).
  2. Am I a candidate for Trastuzumab deruxtecan, Pertuzumab, Tucatinib or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of DESTINY-Breast09 and CLEOPATRA apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, second line

  1. For my situation (metastatic, second line), which of the standard options do you recommend and why?
    Why: Guideline options include: T-DXd if not used first line (DESTINY-Breast03, PFS HR 0.33 vs T-DM1); tucatinib + trastuzumab + capecitabine, especially with brain metastases (HER2CLIMB).
  2. Am I a candidate for Trastuzumab deruxtecan, Tucatinib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of DESTINY-Breast03 and HER2CLIMB apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, later lines

  1. For my situation (metastatic, later lines), which of the standard options do you recommend and why?
    Why: Guideline options include: T-DM1; neratinib or lapatinib + capecitabine; margetuximab + chemotherapy; trastuzumab + chemotherapy (continued HER2 blockade); zanidatamab and Chinese ADCs (trastuzumab rezetecan, disitamab vedotin) where available; trials.
  2. Am I a candidate for Trastuzumab emtansine, Neratinib, Lapatinib or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Brain metastases

  1. For my situation (brain metastases), which of the standard options do you recommend and why?
    Why: Guideline options include: Systemic: tucatinib triplet or T-DXd (DESTINY-Breast12, intracranial ORR 72%); local: stereotactic radiosurgery or surgery for symptomatic or large lesions; whole-brain RT reserved.
  2. Am I a candidate for Tucatinib, Trastuzumab deruxtecan, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of HER2CLIMB and DESTINY-Breast12 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Cardiac monitoring and survivorship

  1. For my situation (cardiac monitoring and survivorship), which of the standard options do you recommend and why?
    Why: Guideline options include: LVEF every 3 months during anti-HER2 therapy; hold and cardioprotect for declines; anthracycline-free regimens preferred; long-term surveillance for late recurrence in HR+/HER2+.
  2. How do the results of PERSEPHONE apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Any stage

  1. Are there clinical trials I could join, for example of HER2 PET, Zanidatamab, Disitamab vedotin, Trastuzumab rezetecan?
    Why: Trials are how the next standard of care is set; asking early keeps options open.
  2. 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.
  3. 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.
  4. I read that “Brain metastases in ~50% of metastatic patients”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “Which patients can skip chemotherapy entirely”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.

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

17
Antibody-drug conjugate (ADC)Bispecific antibodiesCardio-oncologyCDK4/6 inhibitorsCytotoxic chemotherapyDietitian-led weight-loss programmes in HR-positive breast cancerFDG PETFluorescence-guided surgeryHER2 PETMammography & tomosynthesisMonoclonal antibodiesMRD / molecular residual disease testingOptical & fluorescence imagingSBRT / SABR (stereotactic radiotherapy)Site-specific conjugation & linker chemistrySmall-molecule kinase inhibitorsTopoisomerase-I inhibitors (and ADC payloads)

targets

5
CDK4/6EGFRHER2HER3PIK3CA / PI3K-alpha

drugs

20
Phase 3ADC
ARX788
Not filedADC
Disitamab vedotin
ApprovedSmall-molecule PI3Kα inhibitor and degrader
Inavolisib · Itovebi
ApprovedSmall-molecule reversible HER2/EGFR kinase inhibitor
Lapatinib · Tykerb
ApprovedFc-engineered monoclonal antibody (anti-HER2)
Margetuximab · Margenza
ApprovedSmall-molecule irreversible pan-HER kinase inhibitor
Neratinib · Nerlynx
ApprovedCytotoxic chemotherapy (taxane)
Paclitaxel / nab-paclitaxel · Taxol / Abraxane
ApprovedSmall-molecule CDK4/6 inhibitor
Palbociclib · Ibrance
Not mapped hereProtease-activated fluorescent imaging agent
Pegulicianine · Lumisight
ApprovedMonoclonal antibody (anti-HER2, dimerisation domain)
Pertuzumab · Perjeta; Phesgo (with trastuzumab, subcutaneous)
Not filedSmall-molecule irreversible pan-HER kinase inhibitor
Pyrotinib · Airuini
ApprovedMonoclonal antibody (anti-HER2)
Trastuzumab · Herceptin (and biosimilars, Phesgo with pertuzumab)
ApprovedBiosimilar monoclonal antibody (anti-HER2)
Trastuzumab biosimilars · Ogivri, Herzuma, Kanjinti, Trazimera, Ontruzant, Hercessi
Phase 3ADC
Trastuzumab brengitecan
ApprovedADC
Trastuzumab deruxtecan · Enhertu
WithdrawnADC
Trastuzumab duocarmazine
ApprovedADC
Trastuzumab emtansine · Kadcyla
Not mapped hereADC
Trastuzumab rezetecan
ApprovedSmall-molecule kinase inhibitor (HER2)
Tucatinib · Tukysa
ApprovedBiparatopic bispecific antibody (HER2)
Zanidatamab · Ziihera

companies

14
AstraZenecaBeOne Medicines (formerly BeiGene)Daiichi SankyoJazz PharmaceuticalsJiangsu Hengrui PharmaceuticalsJohnson & JohnsonMacroGenicsNovartisPfizer (incl. Seagen)Puma BiotechnologyRemeGenRoche / GenentechSystImmune / Sichuan BiokinZymeworks

institutions

27
Austrian Breast & Colorectal Cancer Study GroupBreast Cancer Research FoundationBreast Cancer TrialsBreast International Group (BIG)Centre Léon BérardChampalimaud Foundation – Champalimaud Clinical CentreDuke Cancer InstituteETOP IBCSG Partners FoundationGEICAM Spanish Breast Cancer GroupGeorgetown Lombardi Comprehensive Cancer CenterHospital del Mar / Hospital del Mar Research InstituteIEO – European Institute of OncologyInstitut Jules BordetInstituto Alexander FlemingIRCCS Ospedale San RaffaeleIstituto di Candiolo IRCCS – FPOIstituto Oncologico Veneto IRCCSKorean Cancer Study GroupMayo Clinic Comprehensive Cancer Center – FloridaNational Taiwan University HospitalNSABP FoundationRosalind and Morris Goodman Cancer Institute, McGill UniversitySOLTI Cancer Research GroupTianjin Medical University Cancer Institute and HospitalUnion Hospital, Tongji Medical CollegeWeizmann Institute of ScienceWest Japan Oncology Group

pathways

5
p53 / RB / cell-cycle checkpointPI3K / AKT / mTORRAS / RAF / MEK / ERK (MAPK)Receptor tyrosine kinase activationThe blood–brain barrier & brain metastasis

terms

12
ADC sequencingBiosimilarBrain metastases (intracranial disease)Deauville score and PET-adapted therapyDual HER2 blockadeHER2-positive (IHC 3+ or ISH-amplified)HER2-positive brain metastasesInterstitial lung disease (ILD) / pneumonitisLumpectomy (breast-conserving surgery)MastectomyPathologic complete response (pCR)Trastuzumab cardiotoxicity

trials

18
ACE-Breast-02APHINITYAPT (adjuvant paclitaxel-trastuzumab)BWEL (Breast Cancer Weight Loss, Alliance A011401)CLEOPATRADESTINY-Breast03DESTINY-Breast05DESTINY-Breast09DESTINY-Breast11DESTINY-Breast12HER2CLIMBHER2CLIMB-02HER2CLIMB-05HERA, NSABP B-31 & NCCTG N9831 (adjuvant trastuzumab)HORIZON-Breast01KATHERINEPERSEPHONEPHERGain

pairings

2
Early FDG-PET response → chemotherapy omission (HER2+)Tucatinib + trastuzumab + capecitabine for brain metastases

roadmaps

1
ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs

ideas

19
A risk-stratified cardio-oncology pathway for everyone receiving heart-toxic cancer therapyA standard platform to get drugs into the brain: focused ultrasound plus shuttle-engineered therapeuticsAn organotropism atlas that predicts where a cancer will spreadBiomarker-guided cardioprotection for everyone on cardiotoxic cancer therapyBrain metastases included by default in every solid-tumour trialBuild a human model of the barrier that guards the brain fluidCan T-DXd alone cure early HER2-positive disease?Deliver CAR-T cells straight into the fluid around the brainOne-stop breast clinics: imaging, biopsy and a preliminary answer in a single visitPrevention trials aimed only at brain metastasisPublic country dashboards for the three WHO breast cancer targetsRe-test the metastasis, not the old primary, before every change of treatmentRead the spinal fluid to track brain tumours without opening the skullReduce the dose once the cancer responds: response-adapted de-escalation trialsSequencing HER2 ADCs by payload after T-DXdSystemic-first management of HER2-positive brain metastasesTreat brain metastases as a disease with its own trials programmeUse the brain's own transport door to carry antibody drugs acrossWHO prequalification plus pooled demand to push biosimilar prices below 10% of the originator

collections

1
Susan G. Komen

people

29
Andrew WardleyBarbara BradfieldBinghe XuCarlos BarriosCharles E. Geyer Jr.Clifford A. HudisDavid CameronDebu TripathyDennis J. SlamonEvandro de AzambujaFei MaGunter von MinckwitzJame AbrahamJavier CortésJoaquín ArribasJonas BerghJoohyuk SohnKan YonemoriLaura J. EssermanMartine PiccartNancy U. LinSara A. HurvitzSara López-TarruellaSara M. TolaneyShinji OhnoSibylle LoiblSung-Bae KimThomas BachelotYeon Hee Park

bottlenecks

6
Biomarkers are not validated or standardisedKnowledge reaches practice too slowlyMost of the world has almost no cancer careSurvivorship and late effects are neglectedThe brain: barrier and sanctuaryWrong doses

key papers

3
DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancerKATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatmentMASAI: AI-supported mammography screening finds more cancers with half the radiologist workload

Key papers

3top
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-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer

For HER2-positive metastatic breast cancer that has progressed after trastuzumab and a taxane, trastuzumab deruxtecan is now the standard second-line treatment and T-DM1 has moved later in the sequence. The benefit is large enough that ADC design, not just the target, is understood to be what matters. Patients need lung monitoring because of the risk of pneumonitis.

rctNew England Journal of Medicine 2019changed practice
KATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatment

HER2-positive breast cancer is now routinely treated before surgery so that the pathology result can guide what comes after: patients with no residual cancer continue trastuzumab (with or without pertuzumab), while those with residual disease switch to T-DM1. This model of using the tumour's response as a test has since been copied in triple-negative and other cancers.

Latest papers

top
Literature trend491 papers in the last 12 months+7% vs prior 12How this is computed
Latest papers · live from Europe PMC
Open in Europe PMC

Query for this cancer: (TITLE:"HER2-positive breast cancer" OR ABSTRACT:"HER2-positive breast cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about HER2-positive breast cancer, not a curated reading list.

Connected

173top

Pages like this

not linked directly; found by shared links

technologies

13
Antibody-drug conjugate (ADC)Bispecific antibodiesCardio-oncologyCDK4/6 inhibitorsDietitian-led weight-loss programmes in HR-positive breast cancerFDG PETHER2 PETMammography & tomosynthesisMonoclonal antibodiesMRD / molecular residual disease testingSBRT / SABR (stereotactic radiotherapy)Site-specific conjugation & linker chemistrySmall-molecule kinase inhibitors

targets

5
CDK4/6EGFRHER2HER3PIK3CA / PI3K-alpha

drugs

20
Phase 3ADC
ARX788
Not filedADC
Disitamab vedotin
ApprovedSmall-molecule PI3Kα inhibitor and degrader
Inavolisib · Itovebi
ApprovedSmall-molecule reversible HER2/EGFR kinase inhibitor
Lapatinib · Tykerb
ApprovedFc-engineered monoclonal antibody (anti-HER2)
Margetuximab · Margenza
ApprovedSmall-molecule irreversible pan-HER kinase inhibitor
Neratinib · Nerlynx
ApprovedCytotoxic chemotherapy (taxane)
Paclitaxel / nab-paclitaxel · Taxol / Abraxane
ApprovedSmall-molecule CDK4/6 inhibitor
Palbociclib · Ibrance
Not mapped hereProtease-activated fluorescent imaging agent
Pegulicianine · Lumisight
ApprovedMonoclonal antibody (anti-HER2, dimerisation domain)
Pertuzumab · Perjeta; Phesgo (with trastuzumab, subcutaneous)
Not filedSmall-molecule irreversible pan-HER kinase inhibitor
Pyrotinib · Airuini
ApprovedMonoclonal antibody (anti-HER2)
Trastuzumab · Herceptin (and biosimilars, Phesgo with pertuzumab)
ApprovedBiosimilar monoclonal antibody (anti-HER2)
Trastuzumab biosimilars · Ogivri, Herzuma, Kanjinti, Trazimera, Ontruzant, Hercessi
Phase 3ADC
Trastuzumab brengitecan
ApprovedADC
Trastuzumab deruxtecan · Enhertu
WithdrawnADC
Trastuzumab duocarmazine
ApprovedADC
Trastuzumab emtansine · Kadcyla
Not mapped hereADC
Trastuzumab rezetecan
ApprovedSmall-molecule kinase inhibitor (HER2)
Tucatinib · Tukysa
ApprovedBiparatopic bispecific antibody (HER2)
Zanidatamab · Ziihera

companies

12
AstraZenecaDaiichi SankyoJazz PharmaceuticalsJiangsu Hengrui PharmaceuticalsJohnson & JohnsonMacroGenicsPfizer (incl. Seagen)Puma BiotechnologyRemeGenRoche / GenentechSystImmune / Sichuan BiokinZymeworks

institutions

27
Austrian Breast & Colorectal Cancer Study GroupBreast Cancer Research FoundationBreast Cancer TrialsBreast International Group (BIG)Centre Léon BérardChampalimaud Foundation – Champalimaud Clinical CentreDuke Cancer InstituteETOP IBCSG Partners FoundationGEICAM Spanish Breast Cancer GroupGeorgetown Lombardi Comprehensive Cancer CenterHospital del Mar / Hospital del Mar Research InstituteIEO – European Institute of OncologyInstitut Jules BordetInstituto Alexander FlemingIRCCS Ospedale San RaffaeleIstituto di Candiolo IRCCS – FPOIstituto Oncologico Veneto IRCCSKorean Cancer Study GroupMayo Clinic Comprehensive Cancer Center – FloridaNational Taiwan University HospitalNSABP FoundationRosalind and Morris Goodman Cancer Institute, McGill UniversitySOLTI Cancer Research GroupTianjin Medical University Cancer Institute and HospitalUnion Hospital, Tongji Medical CollegeWeizmann Institute of ScienceWest Japan Oncology Group

pathways

5
p53 / RB / cell-cycle checkpointPI3K / AKT / mTORRAS / RAF / MEK / ERK (MAPK)Receptor tyrosine kinase activationThe blood–brain barrier & brain metastasis

terms

12
ADC sequencingBiosimilarBrain metastases (intracranial disease)Deauville score and PET-adapted therapyDual HER2 blockadeHER2-positive (IHC 3+ or ISH-amplified)HER2-positive brain metastasesInterstitial lung disease (ILD) / pneumonitisLumpectomy (breast-conserving surgery)MastectomyPathologic complete response (pCR)Trastuzumab cardiotoxicity

trials

18
ACE-Breast-02APHINITYAPT (adjuvant paclitaxel-trastuzumab)BWEL (Breast Cancer Weight Loss, Alliance A011401)CLEOPATRADESTINY-Breast03DESTINY-Breast05DESTINY-Breast09DESTINY-Breast11DESTINY-Breast12HER2CLIMBHER2CLIMB-02HER2CLIMB-05HERA, NSABP B-31 & NCCTG N9831 (adjuvant trastuzumab)HORIZON-Breast01KATHERINEPERSEPHONEPHERGain

pairings

2
Early FDG-PET response → chemotherapy omission (HER2+)Tucatinib + trastuzumab + capecitabine for brain metastases

roadmaps

1
ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs

ideas

19
A risk-stratified cardio-oncology pathway for everyone receiving heart-toxic cancer therapyA standard platform to get drugs into the brain: focused ultrasound plus shuttle-engineered therapeuticsAn organotropism atlas that predicts where a cancer will spreadBiomarker-guided cardioprotection for everyone on cardiotoxic cancer therapyBrain metastases included by default in every solid-tumour trialBuild a human model of the barrier that guards the brain fluidCan T-DXd alone cure early HER2-positive disease?Deliver CAR-T cells straight into the fluid around the brainOne-stop breast clinics: imaging, biopsy and a preliminary answer in a single visitPrevention trials aimed only at brain metastasisPublic country dashboards for the three WHO breast cancer targetsRe-test the metastasis, not the old primary, before every change of treatmentRead the spinal fluid to track brain tumours without opening the skullReduce the dose once the cancer responds: response-adapted de-escalation trialsSequencing HER2 ADCs by payload after T-DXdSystemic-first management of HER2-positive brain metastasesTreat brain metastases as a disease with its own trials programmeUse the brain's own transport door to carry antibody drugs acrossWHO prequalification plus pooled demand to push biosimilar prices below 10% of the originator

collections

1
Susan G. Komen

people

29
Andrew WardleyBarbara BradfieldBinghe XuCarlos BarriosCharles E. Geyer Jr.Clifford A. HudisDavid CameronDebu TripathyDennis J. SlamonEvandro de AzambujaFei MaGunter von MinckwitzJame AbrahamJavier CortésJoaquín ArribasJonas BerghJoohyuk SohnKan YonemoriLaura J. EssermanMartine PiccartNancy U. LinSara A. HurvitzSara López-TarruellaSara M. TolaneyShinji OhnoSibylle LoiblSung-Bae KimThomas BachelotYeon Hee Park

bottlenecks

6
Biomarkers are not validated or standardisedKnowledge reaches practice too slowlyMost of the world has almost no cancer careSurvivorship and late effects are neglectedThe brain: barrier and sanctuaryWrong doses

key papers

3
DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancerKATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatmentMASAI: AI-supported mammography screening finds more cancers with half the radiologist workload