Latest Cancer TreatmentsDr. Mohammadreza Dabiri
Dr. Mohammadreza Dabiriفارسی

Treating HER2-positive breast cancer: from the worst type to one of the most treatable

Trastuzumab and the drugs that followed it, treatment before surgery, and what "HER2-low" means for treatment

Updated: 28 October 20262 min read11 references
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Key points

  • About 3 in 10 breast cancers have a lot of HER2, and before anti-HER2 drugs these patients relapsed sooner and died sooner [1].
  • Adding trastuzumab to chemotherapy after surgery cut the risk of death by about a third [3].
  • If tumour is still left after treatment before surgery, the drug after surgery is changed, and this has nearly halved the risk of relapse [6, 8].
  • "HER2-low" matters too: in disease that has spread, trastuzumab deruxtecan (Enhertu) also lengthened life in these patients [11].

The story of HER2

In 1987 researchers saw that in about 3 in 10 breast cancers, a gene called HER2 was copied many times over, and these patients relapsed sooner and died sooner; HER2 was one of the strongest signs of a poor prognosis [1].

The same discovery also pointed to a treatment. The antibody trastuzumab was made to stick to exactly this protein. In disease that had spread, adding it to chemotherapy lengthened patients' lives [2]. When it was given after surgery, the result was even bigger: relapse was cut by about half and the risk of death by about a third [3]; another large study also saw fewer relapses [4].

Since then new drugs have followed one after another: pertuzumab, which with trastuzumab in disease that has spread usually added more than a year to patients' lives [5], and drugs that deliver chemotherapy straight to the HER2-positive cell (antibody–drug conjugates).

3 in 10
Breast cancers with a lot of HER2
[1]
A third
Reduction in the risk of death with trastuzumab after surgery
[3]
89 vs 84
In every 100 patients with residual tumour, alive after 7 years
Trastuzumab emtansine versus trastuzumab [7]

Treatment today at each stage

  1. 1

    A small tumour

    Sometimes surgery first and then drugs; your doctor decides based on size and lymph nodes.

  2. 2

    A larger tumour or affected lymph nodes: drugs before surgery

    Chemotherapy with anti-HER2 drugs is given before surgery; this both shrinks the tumour and shows what treatment is needed after surgery [6].

  3. 3

    If tumour is still left after that

    Instead of continuing trastuzumab, trastuzumab emtansine is given: relapse was almost halved and more patients survived [6, 7]. The newer drug trastuzumab deruxtecan lowered the risk of relapse in these patients even further [8].

  4. 4

    The whole course of anti-HER2 treatment

    Usually one year [3, 4]; a heart echo is done before and during treatment (trastuzumab).

  5. 5

    Disease that has spread

    Two antibodies with chemotherapy were the first treatment for years [5]; the combination of trastuzumab deruxtecan and pertuzumab kept the disease quiet much longer, usually more than 3 years [10]. In later treatments too, trastuzumab deruxtecan has lengthened life [9].

What does "HER2-low" mean?

Many breast cancers reported as "HER2-negative" have a small amount of HER2. Until a few years ago this difference did not matter; but in disease that has spread, trastuzumab deruxtecan also controlled the disease better and lengthened life in these patients [11]. If your disease has spread, ask whether your HER2 report is exactly "zero" or "low".

Three important questions for your doctor
  • "Is my tumour HER2-positive, HER2-low or HER2-zero?"
  • "Is treatment before surgery better for me?"
  • "If tumour is left after surgery, what is the next treatment?" [6]

When should I call my doctor?

Report breathlessness, swollen legs or a racing heart (a possible effect on the heart) straight away, and with trastuzumab deruxtecan, a new cough or breathlessness (lung inflammation) [8, 9]. These drugs carry risks in pregnancy; use contraception.

Frequently asked questions

Does HER2-positive mean a worse cancer?

Before anti-HER2 drugs, yes [1]; today, with these drugs, the results of treating this type have become much better [3, 7].

Do anti-HER2 drugs make hair fall out?

Hair loss is mostly due to the chemotherapy given with them; in a large study, adding pertuzumab did not increase hair loss [5] (hair loss).

For physicians

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For physicians

Slamon 1987: HER2 amplification in 30%, an independent predictor of overall survival and time to relapse [1]. B-31/N9831: HR for disease-free survival 0.48 and a 33% reduction in the risk of death [3]. HERA [4]. CLEOPATRA: median OS 56.5 versus 40.8 months [5]. KATHERINE: 3-year iDFS 88.3% versus 77.0% [6]; 7-year OS 89.1% versus 84.4% (HR 0.66) [7]. DESTINY-Breast05: T-DXd versus T-DM1 in residual disease, 3-year iDFS 92.4% versus 83.7% (HR 0.47); ILD 9.6% [8]. DESTINY-Breast09: T-DXd + pertuzumab versus THP, median PFS 40.7 versus 26.9 months [10]. DESTINY-Breast04 (HER2-low): median OS 23.4 versus 16.8 months [11]. Doses: THP and HER2 regimens on the breast cancer page.

Scientific evidence

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Scientific evidence

9 items
Clinical trial

Trastuzumab plus Adjuvant Chemotherapy for Operable HER2-Positive Breast Cancer

N Engl J Med · 2005
133 events in the trastuzumab group vs 261 events in the control group (total 394)Number of events (recurrence, second primary cancer or death before recurrence) up to 15 March 2005
Summary
Clinical trial

Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast Cancer

N Engl J Med · 2005
127 events with trastuzumab vs 220 events in the observation group (347 in total)Number of events at the first interim analysis (median follow-up one year)
Summary
Clinical trial · Phase 3

Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer

N Engl J Med · 2015
56.5 months vs 40.8 monthsMedian overall survival
Summary
Clinical trial · Phase 3

Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer

N Engl J Med · 2025
8.4 yearsMedian follow-up
Summary
Clinical trial · Phase 3

Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer

N Engl J Med · 2026
92.4% vs 83.7%3-year invasive disease-free survival
Summary
Clinical trial · Phase 3

Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer: long-term survival analysis of the DESTINY-Breast03 trial

Nat Med · 2024
52.6 vs 42.7 monthsMedian overall survival
Summary
Clinical trial · Phase 3

Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer

N Engl J Med · 2026
40.7 vs 26.9 monthsMedian progression-free survival
Summary
Clinical trial · Phase 3

Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer

N Engl J Med · 2022
10.1 vs 5.4 monthsProgression-free survival (hormone receptor-positive)
Summary
Clinical trial · Phase 3

Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer

N Engl J Med · 2019
88.3% vs 77.0%3-year iDFS
Summary

Read more

Related cancer types

Breast cancer

Treatment guides

Chemotherapy or targeted therapy? Ask this before treatment startsLate diagnosis costs lives: 5 simple steps to find cancer earlyComplete, on-time, uninterrupted treatment: a simple way to live longerTreating hormone receptor-positive breast cancer (HR+/HER2−): hormone therapy and CDK4/6 inhibitorsWhat is the best treatment for triple-negative breast cancer?

References

11 references
Show all references, 10 with a study cardClose the reference list

Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.

  1. 1
    Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogeneSlamon DJ, Clark GM, Wong SG, et al · Science · 1987;235:177-182
    DOIPubMed Back to text: 1 2 3 4 5
  2. 2
    Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al · N Engl J Med · 2001;344:783-792
    Study cardDOIPubMed Back to text
  3. 3
    Trastuzumab plus Adjuvant Chemotherapy for Operable HER2-Positive Breast CancerRomond EH, Perez EA, Bryant J, Suman VJ, Geyer CE, Davidson NE, et al · N Engl J Med · 2005;353:1673-1684
    Study cardDOIPubMed Back to text: 1 2 3 4 5 6
  4. 4
    Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast CancerPiccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al · N Engl J Med · 2005;353:1659-1672
    Study cardDOIPubMed Back to text: 1 2 3
  5. 5
    Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast CancerSwain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, et al · N Engl J Med · 2015;372:724-734
    Study cardDOIPubMed Back to text: 1 2 3 4
  6. 6
    Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancervon Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al · N Engl J Med · 2019;380:617-628
    Study cardDOIPubMed Back to text: 1 2 3 4 5
  7. 7
    Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast CancerGeyer CE Jr, Untch M, Huang CS, Mano MS, Mamounas EP, Wolmark N, et al · N Engl J Med · 2025;392:249-257
    Study cardDOIPubMed Back to text: 1 2 3 4
  8. 8
    Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast CancerLoibl S, Park YH, Shao Z, et al · N Engl J Med · 2026;394:845-857
    Study cardDOIPubMed Back to text: 1 2 3 4
  9. 9
    Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer: long-term survival analysis of the DESTINY-Breast03 trialCortés J, Hurvitz SA, Im SA, Iwata H, Curigliano G, Kim SB, et al · Nat Med · 2024;30:2208-2215
    Study cardDOIPubMed Back to text: 1 2
  10. 10
    Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast CancerTolaney SM, Jiang Z, Zhang Q, et al · N Engl J Med · 2026;394:551-562
    Study cardDOIPubMed Back to text: 1 2
  11. 11
    Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast CancerModi S, Jacot W, Yamashita T, et al · N Engl J Med · 2022;387:9-20
    Study cardDOIPubMed Back to text: 1 2 3

This page is based on reputable scientific sources and was last updated on 28 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.

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