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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.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
15-20% of breast cancers (roughly 400,000 cases per year worldwide).
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
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.
Same organ: Triple-negative breast cancer (TNBC), Breast cancer (all types), HR-positive / HER2-negative 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, Metastatic triple-negative breast cancer, Basal-like 1 triple-negative breast cancer (BL1), Basal-like 2 triple-negative breast cancer (BL2), Mesenchymal triple-negative breast cancer (M), Mesenchymal stem-like triple-negative breast cancer (MSL), Luminal androgen receptor triple-negative breast cancer (LAR), Immunomodulatory triple-negative breast cancer (IM), Metaplastic breast carcinoma, Carcinoma with medullary pattern (medullary breast cancer), Adenoid cystic carcinoma of the breast, Apocrine carcinoma of the breast, Secretory carcinoma of the breast, BRCA-associated triple-negative breast cancer, Inflammatory breast cancer, Paget disease of the nipple, Phyllodes tumour of the breast, Invasive lobular carcinoma of the breast, Invasive breast carcinoma of no special type (invasive ductal carcinoma), Tubular carcinoma of the breast, Mucinous carcinoma of the breast, Papillary carcinomas of the breast (encapsulated, solid and invasive papillary), Invasive cribriform carcinoma of the breast, Invasive micropapillary carcinoma of the breast, Neuroendocrine neoplasms of the breast, Lobular carcinoma in situ (LCIS)
Most people reading this do not have advanced disease. The map describes what can happen over the whole course of the illness, across autopsy and registry series; today's staging scans find spread earlier, and each site has treatments, from focused radiotherapy for a few spots to drugs that reach the brain.
What helpsT-DXd with pertuzumab first line; tucatinib and T-DXd reach brain metastases, so radiation can often be deferred; palbociclib maintenance for HR-positive disease.
Background: HER2-positive brain metastases, The blood-brain barrier & brain metastasis. Also on OnCo: Atlas of advanced disease · How cancer spreads: the metastasis stages.
Brain metastases occur in a large share of patients over the disease course; CNS activity of newer anti-HER2 drugs matters.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Surgery then weekly paclitaxel × 12 + trastuzumab × 1 year (APT); T-DM1 × 17 cycles is an alternative (ATEMPT). Endocrine therapy if HR+.
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.
Complete 1 year of trastuzumab (± pertuzumab if node-positive at diagnosis); endocrine therapy if HR+; radiation per stage.
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.
Chemotherapy + trastuzumab + pertuzumab for 1 year (APHINITY); trastuzumab alone for lower risk; 6 months acceptable where resources are limited (PERSEPHONE).
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).
T-DXd if not used first line (DESTINY-Breast03, PFS HR 0.33 vs T-DM1); tucatinib + trastuzumab + capecitabine, especially with brain metastases (HER2CLIMB).
T-DM1; neratinib or lapatinib + capecitabine; margetuximab + chemotherapy; trastuzumab + chemotherapy (continued HER2 blockade); zanidatamab and Chinese ADCs (trastuzumab rezetecan, disitamab vedotin) where available; trials.
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.
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+.
Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year.
The targets of this cancer's medicines and the ones linked to it directly.
| Target / alteration | Prevalence | Measure | Source |
|---|---|---|---|
| HER2 | 100% | IHC 3+ or ISH-amplified (defining) | Nature |
| Topoisomerase II alpha (TOP2A) Co-amplified tumours gained most from anthracycline-containing chemotherapy | about 35% | TOP2A co-amplification with HER2, FISH, 4,943 breast cancers analysed | doi.org |
How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.
4 cell lines, 1 mouse models and 6 repositories are listed for this cancer. See them →
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask.
Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record.
Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked.