Breast Care A-Z · Concept · HER2

HER2

also: HER2 positive, HER2 negative, HER2 status, human epidermal growth factor receptor 2, ERBB2 · pronounced H-E-R-two

HER2 is a protein that can make some breast cancers grow faster; cancers with high levels are called HER2-positive and respond to specific, effective targeted treatments. You may have been told your cancer is HER2-positive or negative — it is one of three key features pathologists report, alongside [ER](/glossary/oestrogen-receptor/) and grade.

Quick answers

Is HER2-positive breast cancer worse than HER2-negative?

Historically yes — HER2-positive cancers were considered more aggressive. With modern targeted therapy, outcomes for HER2-positive cancer have improved to be comparable to or better than HER2-negative cancers of similar stage and grade. The HER2-positive label is no longer the prognostic mark it once was, because of the effectiveness of targeted treatment.

How long is the targeted antibody treatment?

Adjuvant trastuzumab is typically given for 12 months (alongside chemotherapy and continued afterwards). Pertuzumab, when added, is given alongside trastuzumab. Newer agents have different schedules.

Will the targeted treatment have side effects?

Trastuzumab is generally well tolerated. The main concern is heart function — trastuzumab can occasionally affect the heart's pumping ability, which is why echocardiograms are done during treatment. The effect is usually reversible. Other side effects (mild flu-like symptoms, fatigue) are usually less significant than chemotherapy side effects.

BREASTORY ENCYCLOPEDIA · PLATE XLIII ONCOLOGY · MOLECULAR SUBTYPES HER2-positive breast cancer HER2 · ERBB2 · human epidermal growth factor receptor 2 gene amplification and protein overexpression driving aggressive tumour growth, targetable with precision biological therapies i FIG 01 Cell Membrane · HER2 Receptor Diagram · Signalling Cascade EXTRACELLULAR SPACE CELL MEMBRANE INTRACELLULAR / CYTOPLASM Trastuzumab Nucleus HER2 gene 17q12 HER2 gene amplified (17q12) RAS RAF MEK ERK Proliferation PI3K AKT mTOR Survival i HER2 receptor (×30–100 fold) ii HER2 gene amp (chr 17q12) iii Receptor dimerisation iv Trastuzumab (domain IV) v PI3K/AKT/mTOR pathway IHC SCORING IHC 0 / 1+ → HER2 negative IHC 2+ → equivocal → FISH required IHC 3+ → HER2 positive (>10% strong) FISH: HER2/CEP17 ratio ≥2.0 = amplified Complete membrane staining criterion applies to >10% of tumour cells (IHC 3+) Retesting advised on discordant samples per ASCO/CAP 2018 guidelines TARGETED THERAPY Trastuzumab + pertuzumab Dual blockade · neoadjuvant/adjuvant T-DM1 / T-DXd (ADCs) Residual disease / metastatic setting Lapatinib / neratinib (TKIs) Adjuvant / later lines of treatment Selection guided by residual disease status ii FIG 02 HER2-positive vs HER2-negative Disease Parameter HER2-positive HER2-negative HER2 IHC 3+ (or 2+ FISH+) 0 or 1+ Prevalence ~20% of breast cancers ~80% Prognosis (untreated) Aggressive Grade-dependent Targeted therapy Yes (anti-HER2) No Neoadjuvant pCR ~50–65% dual anti-HER2 Lower Hormone receptor ~50% co-positive Variable Grade Often grade 3 Variable 5-yr survival (early) ~90%+ with treatment Variable Key drugs Trastuzumab, pertuzumab Chemo, hormone BRCA association Uncommon More common TNBC iii FIG 03 IHC Scoring Guide · FISH Interpretation IHC Score Staining Pattern HER2 Status / Action 0 No staining Negative / No anti-HER2 1+ Faint incomplete membrane Negative (HER2-low) 2+ equivocal Weak–moderate complete Equivocal / FISH required 2+ FISH amplified HER2/CEP17 ratio ≥2.0 Positive / Anti-HER2 2+ FISH not amplified Ratio <2.0 Negative / No anti-HER2 3+ Strong complete membrane Positive / Anti-HER2 FISH amp (any IHC) Copies ≥6 or ratio ≥2 Positive / Anti-HER2 HER2-low (1+/2+FISH−) Low expression HER2-low / T-DXd eligible Retesting Discordant result Repeat on new block iv FIG 04 Diagnostic and Treatment Pipeline 1 Diagnosis biopsy + HER2 IHC/FISH 2 Staging CT bone scan 3 Neoadjuvant chemo + trastuzumab + pertuzumab 4 Surgery WLE/mastectomy + SLNB 5 Adjuvant T-DM1 (residual) or HP (pCR) 6 Surveillance imaging + bloods v FIG 05 Anti-HER2 Therapy Drug Reference Trastuzumab Herceptin Pertuzumab Perjeta T-DM1 Kadcyla T-DXd Enhertu Lapatinib Tykerb Neratinib Nerlynx vi FIG 06 Key Statistics · HER2-positive Disease ~20% of breast cancers HER2+ [1] ~65% pCR dual anti-HER2 + chemo [2] ~90%+ 5-yr survival early HER2+ [3] ~40% reduction in recurrence [4] vii FIG 07 References 1. Slamon DJ et al. HER2 overexpression. Science 1987;235:177 2. Gianni L et al. NeoSphere trial. Lancet Oncol 2012;13:25 3. Piccart-Gebhart MJ et al. HERA trial. NEJM 2005;353:1659 4. Cameron D et al. 11-yr HERA follow-up. Lancet 2017;389:1195 5. Modi S et al. DESTINY-Breast04. NEJM 2022;387:9 Clinically authored by Dr Fiona Tsang-Wright , FRCS (Gen Surg) GMC 4549831 · ORCID 0000-0003-4801-026X
Visual Reference · HER2
Open full size ↗
Definition
HER2 is a protein on the surface of cells that, when present in unusually high amounts, drives cancer cell growth — and breast cancers that test "HER2-positive" can be effectively treated with targeted antibody therapies that block this protein.

Common questions The questions patients ask first

Is HER2-positive breast cancer worse than HER2-negative?
Historically yes — HER2-positive cancers were considered more aggressive. With modern targeted therapy, outcomes for HER2-positive cancer have improved to be comparable to or better than HER2-negative cancers of similar stage and grade6. The HER2-positive label is no longer the prognostic mark it once was, because of the effectiveness of targeted treatment.
How long is the targeted antibody treatment?
Adjuvant trastuzumab is typically given for 12 months (alongside chemotherapy and continued afterwards)1. Pertuzumab, when added, is given alongside trastuzumab7. Newer agents have different schedules.
Will the targeted treatment have side effects?
Trastuzumab is generally well tolerated. The main concern is heart function — trastuzumab can occasionally affect the heart's pumping ability9, which is why echocardiograms are done during treatment10. The effect is usually reversible9. Other side effects (mild flu-like symptoms, fatigue) are usually less significant than chemotherapy side effects.
Will my children be at higher risk of breast cancer?
HER2 status is a feature of the cancer, not an inherited trait. HER2-positive cancers are not generally a sign of an inherited cancer syndrome. Family history and genetic testing are decided on the broader pattern of cancers in the family — see [BRCA](/glossary/brca/) and [family history](/glossary/family-history/).

HER2 is a protein on the surface of cells that, when present in unusually high amounts, drives cancer cell growth — and breast cancers that test “HER2-positive” can be effectively treated with targeted antibody therapies that block this protein.

Around 15–20% of breast cancers are HER2-positive1. The HER2 status is tested on the biopsy or operation specimen and reported as positive, negative, or “low” (a newer category). Targeted treatment with trastuzumab (Herceptin) and similar antibodies has transformed the outlook for HER2-positive cancer, which used to be considered one of the more aggressive subtypes.

Orientation Why you might be reading about this

You may have been told your cancer is HER2-positive (or negative), or you are reading about what receptor status means. HER2 is one of three key features pathologists report alongside ER and grade — and HER2-positive cancers in particular have specific, effective treatments tied to that status. This page explains what HER2 is, what testing involves, and what positive and negative results mean for treatment.

Related terms: Oestrogen receptor · Invasive ductal carcinoma · Core biopsy · Grade and stage

Definition What HER2 is

HER2 is a normal protein that sits on the surface of many cells in the body. It is part of a family of receptors that respond to growth signals — when activated, it tells the cell to divide. In normal cells, HER2 is present in modest amounts and is well-regulated.

In some breast cancers, the cancer cells produce far more HER2 protein than normal — sometimes 100 times more1. This over-expression is usually caused by extra copies of the HER2 gene (a process called gene amplification) and drives the cancer to grow faster than it otherwise would. Cancers with this feature are called HER2-positive4.

The clinical importance of HER2 is that it is a target for treatment. Antibody drugs that bind to HER2 — most prominently trastuzumab (Herceptin), alongside pertuzumab (Perjeta) and others — block the receptor and effectively switch off its growth signal. These targeted therapies have substantially improved outcomes for HER2-positive breast cancer over the past two decades.

Testing How HER2 is tested

HER2 status is tested on the biopsy or operation specimen as part of routine pathology. Two main testing methods are used:

Immunohistochemistry (IHC)

A staining test that shows how much HER2 protein is on the cell surface. Results are reported as a score from 0 to 3+4:

  • 0 or 1+ — HER2-negative.
  • 2+ — equivocal (uncertain). The result is confirmed with the second test (in situ hybridisation) before a final HER2 status is assigned.
  • 3+ — HER2-positive.

In situ hybridisation (ISH or FISH)

A genetic test that counts how many copies of the HER2 gene are present4. Used to confirm 2+ IHC results, and increasingly used as the primary test in some labs.

A HER2-positive result requires either 3+ on IHC or amplification on ISH4.

“HER2-low” — a newer category

Recent advances in targeted therapy have introduced a third category: HER2-low (IHC 1+ or 2+ without amplification). HER2-low cancers were previously grouped with HER2-negative, but newer drugs (such as trastuzumab deruxtecan / Enhertu) have shown benefit specifically in this group5. Pathology reports increasingly include this distinction.

HER2-positive What HER2-positive means for treatment

For HER2-positive invasive breast cancer, targeted antibody therapy is part of the standard treatment plan:

  • Adjuvant trastuzumab (after surgery), typically for 12 months136, is given to most HER2-positive patients with invasive disease.
  • Pertuzumab is added to trastuzumab for higher-risk cases (larger tumours, lymph node-positive disease)37.
  • Neoadjuvant therapy (chemotherapy plus trastuzumab plus pertuzumab, given before surgery) is increasingly used for HER2-positive cancers larger than 2 cm or with positive lymph nodes3.
  • Newer agents — trastuzumab emtansine (Kadcyla)8, trastuzumab deruxtecan (Enhertu)5 — are used in higher-risk situations or for residual disease after neoadjuvant treatment8.

The combination of chemotherapy and HER2-targeted antibody is a more involved treatment than for HER2-negative cancer, but it is also markedly more effective for the HER2-positive subgroup. Survival outcomes for HER2-positive breast cancer have improved substantially since trastuzumab entered routine use6.

HER2-negative What HER2-negative means

For HER2-negative invasive breast cancer, treatment depends on the other receptor status (ER) and on size, grade, and lymph node involvement. HER2-negative cancers do not benefit from trastuzumab (it does not work without the HER2 target). Treatment is built around hormone therapy (for ER-positive cancers) and chemotherapy where the absolute benefit is meaningful.

A subset of HER2-negative cancers are also ER-negative and PR-negative — known as triple-negative breast cancer (TNBC). TNBC is treated primarily with chemotherapy and, in selected cases, immunotherapy and PARP inhibitors.

At consultation What to discuss at consultation

Once HER2 status is known:

  • What the result means for the proposed treatment plan — particularly whether neoadjuvant chemotherapy plus targeted antibodies is being recommended.
  • The HER2-low category if your IHC was 1+ or 2+ without amplification — this can affect treatment options if the disease ever recurs.
  • The schedule and side effects of trastuzumab, where applicable.
  • Cardiac monitoring during trastuzumab treatment — trastuzumab can affect heart function9 and is monitored with regular echocardiograms10.

If you already have a treatment plan and would like an independent review of what HER2 status means for it, you can book a second-opinion consultation.

Resources Further reading

Sources & guidance

Every figure on this page is anchored to a published source. Tap a number in the text or below to jump to the reference.

  1. review Loibl S, Gianni L. HER2-positive breast cancer. The Lancet. 2017 ;389(10087):2415-2429 doi:10.1016/S0140-6736(16)32417-5 Cited for: HER2 overexpression frequency (~15-20%); adjuvant trastuzumab benefit and 12-month duration standard.
  2. guideline National Institute for Health and Care Excellence (NICE). Early and locally advanced breast cancer: diagnosis and management (NG101). London: NICE. 2018 ;Last updated 2024 https://www.nice.org.uk/guidance/ng101 Cited for: UK pathway for HER2 testing and HER2-targeted adjuvant therapy in early breast cancer.
  3. guidance Wolff AC, Hammond MEH, Allison KH, et al. (American Society of Clinical Oncology / College of American Pathologists). Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO/CAP clinical practice guideline focused update. Journal of Clinical Oncology. 2018 ;36(20):2105–2122 doi:10.1200/JCO.2018.77.8738 Cited for: International standard for HER2 testing — IHC 0/1+/2+/3+ scoring; ISH/FISH confirmation of equivocal results; HER2-positive definition (3+ IHC or amplification on ISH).
  4. rct Modi S, Jacot W, Yamashita T, et al. (DESTINY-Breast04 investigators). Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. New England Journal of Medicine. 2022 ;387(1):9–20 doi:10.1056/NEJMoa2203690 Cited for: Recognition of HER2-low as a clinically actionable category — trastuzumab deruxtecan benefit in IHC 1+/2+ ISH-negative disease.
  5. meta_analysis Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials. Lancet Oncology. 2021 ;22(8):1139-1150 doi:10.1016/S1470-2045(21)00288-6 Cited for: EBCTCG meta-analysis: trastuzumab improves recurrence-free and overall survival in HER2-positive early breast cancer.
  6. rct von Minckwitz G, Procter M, de Azambuja E, et al. (APHINITY Steering Committee). Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. New England Journal of Medicine. 2017 ;377(2):122-131 doi:10.1056/NEJMoa1703643 Cited for: APHINITY trial: adjuvant pertuzumab + trastuzumab in HER2-positive early breast cancer.
  7. rct von Minckwitz G, Huang CS, Mano MS, et al. (KATHERINE Investigators). Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. New England Journal of Medicine. 2019 ;380(7):617-628 doi:10.1056/NEJMoa1814017 Cited for: KATHERINE trial: T-DM1 (ado-trastuzumab emtansine) for residual disease after neoadjuvant therapy in HER2-positive breast cancer.
  8. cohort Ewer MS, Vooletich MT, Durand JB, et al. Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. Journal of Clinical Oncology. 2005 ;23(31):7820-7826 doi:10.1200/JCO.2005.13.300 Cited for: Trastuzumab-related cardiotoxicity is largely reversible with treatment cessation and standard heart failure management.
  9. guideline Curigliano G, Lenihan D, Fradley M, et al. (ESMO Guidelines Committee). Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Annals of Oncology. 2020 ;31(2):171-190 doi:10.1016/j.annonc.2019.10.023 Cited for: ESMO consensus on cardiac monitoring schedule during HER2-targeted therapy (baseline + every 3 months).