About 16% of the 3400 New Zealanders diagnosed with breast cancer each year will have HER2-positive breast cancer.
HER2 stands for 'human epidermal growth factor receptor-type 2'. It is a type of protein that sits on the surface of all normal cells and its job is to send messages to the cell, telling it to grow and replicate.
If you have HER2-positive breast cancer, your cancer cells have an abnormally large number of HER2 proteins on their surface. This means the tumour has the potential to grow and spread at a fast rate. HER2-positive breast cancer tends to be more aggressive than some of the other sub-types.
Fortunately, the HER2 protein can be specifically targeted by some very effective anti-cancer drugs.
Trastuzumab (brand names Herceptin®, Herzuma® and others) is the best known of these and is particularly effective for women with HER2-positive breast cancer. Trastuzumab is a manufactured antibody that binds to the HER2 protein, and blocks the signals that would otherwise cause the cancer to grow. It is designed to specifically target and treat cancers that are HER2 positive.
The role of HER2 in cancer was discovered in 1989 [1] and trastuzumab was developed by 1995. It was first trialled in women with metastatic HER2-positive breast cancer. Trastuzumab (original brand name Herceptin®) significantly improved survival in these patients, and these results led to its approval for this use in 1998. Trials were then carried out to see if trastuzumab could also be used to treat early HER2-positive breast cancer. By 2005, the researchers were able to report that a 12-month treatment with trastuzumab after surgery and chemotherapy could significantly reduce recurrence and improve survival in these patients as well. Extended follow-up of over 4,000 patients confirmed these findings in 2012 [2]. A 12-month treatment programme of trastuzumab has been available in New Zealand for women with HER2-positive breast cancer since 2008.
Trastuzumab is given as an intravenous infusion, usually once every three weeks, for 12 months.
The side effects of trastuzumab are generally mild, with the most common being flu-like symptoms, which usually occur shortly after the drug is given. More serious events, such as allergic reactions and breathing problems occur rarely.
Significant heart problems develop in a few women. Heart failure has occurred in 0.6 per cent of patients when trastuzumab is given following chemotherapy, and up to 4 per cent when given at the same time as taxane-based chemotherapy. In some cases specific drug treatment was required but in most patients, heart function recovered after stopping trastuzumab. The risk of heart failure is greater in women with previous heart problems. Patients must be checked for heart problems before receiving trastuzumab and must have their heart function monitored during treatment.
Several clinical trials have looked at whether trastuzumab could be given over a shorter period than 12 months and still give the same benefits. Recent analyses of the results have concluded that one year of treatment leads to better outcomes than shorter treatments [3,4].
12 months of trastuzumab is still the standard of care (March 2025), and shorter durations of treatment might only be considered where patients cannot tolerate side effects or have heart conditions that make any risk of cardiac toxicity unacceptable.
Herceptin® is the original patented version of trastuzumab, but now that its patents have expired, other companies are manufacturing biosimilar copies of this drug. (For more about trastuzumab biosimilars click here.)
In New Zealand, Herzuma® is the brand of trastuzumab that is currently publicly funded. You can read Medsafe’s consumer information leaflet on Herzuma® here.
Pertuzumab (brand name Perjeta®) is another drug that targets the HER2 protein, but binds to it at a different site from trastuzumab.
In New Zealand, pertuzumab is funded only for women with metastatic HER2-positive breast cancer, to be used in conjunction with trastuzumab.
However, recent research [5, 6] has also shown that pertuzumab can also be useful in treating early HER2-positive breast cancer, especially in cases where the features of the cancer at the time of diagnosis (such as stage, tumour size, nodal involvement) suggest a higher risk of the cancer returning after treatment (recurrence). Pertuzumab can be combined with trastuzumab and chemotherapy in these cases, but the patient will have to pay for pertuzumab and receive it in a private oncology clinic.
Some patients with early HER2-positive breast cancer may benefit from treatment with pertuzumab and trastuzumab before their surgery. This is called neo-adjuvant therapy, which aims to shrink the tumour before surgery. Sometimes tumours treated in this way can become undetectable (called a pathological complete response). This use of pertuzumab is not yet funded in New Zealand but can be paid for privately.
You can read Medsafe’s consumer leaflet on Perjeta® here.
There is currently an application with PHARMAC asking for funding for Perjeta for early breast cancer but as yet no final decision has been made (March 2025).
Trastuzumab emtansine (also known as T-DM1; brand name Kadcyla®) is another anti-HER2 drug. It differs from trastuzumab and pertuzumab in that it is a two-part molecule that uses a trastuzumab molecule to carry a toxin (emtansine, also known as DM1) directly to the cancer cells that have lots of HER2 on their surfaces. There it locks on to the cell and only then releases the ‘payload’ toxin to kill that cell, with minimum collateral damage to other cells. Trastuzumab emtansine (Kadcyla®) is funded in New Zealand for women who have been diagnosed with metastatic HER2-positive breast cancer, have been treated with trastuzumab and perhaps also pertuzumab, but have had their cancer progress.
Recent research has also demonstrated a role for trastuzumab emtansine in the treatment of early HER2-positive breast cancer. In patients at high risk of recurrence, whose tumours did not shrink completely after neoadjuvant treatment with trastuzumab and pertuzumab, adding trastuzumab emtansine to trastuzumab for their treatment after surgery reduced their risk of having a recurrence of invasive breast cancer or death by 50% [7]. Pharmac has now funded trastuzumab emtansine (Kadcyla®) for patients with early HER2-positive breast cancer who are at high risk of recurrence (2022).
You can read the Medsafe consumer information leaflet on Kadcyla® here.
Trastuzumab deruxtecan (also known as T-DXd; brand name Enhertu®) is another two-part anti-HER2 drug, with trastuzumab guiding the attached toxin (deruxtecan) to the HER2 molecules on the surfaces of the cancer cells. In New Zealand, trastuzumab deruxtecan is funded for those with metastatic HER2 positive breast cancer, whose cancer has stopped responding to other anti-HER2 therapy.
You can read the Medsafe consumer information leaflet on Enhertu® here.
Enhertu® has also been found to be useful in treating some other types of breast cancer called ‘HER2-low’ [8] or ‘HER2-ultralow’ [9], but it is not funded for those indications in New Zealand. Pharmac received an application for its use in treating unresectable (the tumour cannot be removed by surgery) or metastatic HER2-low breast cancer in April 2024, but no decision has been made on this yet (March 2025).
Find out more
The pharmaceutical company, Roche, has a website with some useful information about HER2-positive breast cancer, Herceptin®, Perjeta® and Kadcyla®. Visit https://cancertreatments.co.nz/breast-cancer/
References
[1] Slamon et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science, 12 May 1989: Vol. 244, Issue 4905, pp. 707-712. DOI: 10.1126/science.2470152
[2] Perez et al. Trastuzumab Plus Adjuvant Chemotherapy for Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Planned Joint Analysis of Overall Survival From NSABP B-31 and NCCTG N9831. J Clinical Oncology 32, no. 33 (Nov 20, 2014) 3744-3752. https://ascopubs.org/doi/10.1200/JCO.2014.55.5730
[3] Niraula S, Gyawali B. Optimal duration of adjuvant trastuzumab in treatment of early breast cancer: a meta-analysis of randomized controlled trials. Breast Cancer Res Treat. 2019;173(1):103-109. doi:10.1007/s10549-018-4967-8
[4] Deng H, Du X, Wang L, Chen M. Six Months vs. 12 Months of Adjuvant Trastuzumab Among Women With HER2-Positive Early-Stage Breast Cancer: A Meta-Analysis of Randomized Controlled Trials. Front Oncol. 2020;10:288. Published 2020 Mar 20. doi:10.3389/fonc.2020.00288
[5] Gianni L, Pienkowski T, Im Y-H, et al: 5-Year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer NeoSphere: A multicenter, open-label, phase 2 randomised trial. Lancet Oncol 17:791-800, 2016.
[6] Minckwitz et al. Adjuvant Pertuzumab and Trastuzumab in early HER2-Positive Breast Cancer. New England Journal of Medicine 2017; 377: 122-131. https://www.nejm.org/doi/10.1056/NEJMoa1703643
[7] Minckwitz et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. New England Journal of Medicine 2019; 380: 617-628. https://www.nejm.org/doi/full/10.1056/nejmoa1814017
[8] Modi et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. New England Journal of Medicine 2022; 387: 9-20. https://www.nejm.org/doi/full/10.1056/NEJMoa2203690
[9] ASCO 2024 - DESTINY-Breast06: New HER2-ultralow category identified; T-DXd equally beneficial in this subgroup. June 2024. https://oncoxchange.org/view/preview/asco-2024-destiny-breast06-new-her2-ultralow-category-identified-t-dxd-equally-beneficial-in-this-subgroup
28 March 2025
