Trastuzumab, sold as Herceptin and as biosimilars, is an antibody against HER2 that has transformed the outlook for HER2-positive breast cancer and extends survival in HER2-positive stomach cancer. This page covers HER2 testing, where the drug is used, infusion or injection, six versus twelve months, partner drugs, what the trials show, its effect on the heart and how it is monitored, biosimilars, and how patients from abroad arrange treatment in Istanbul.
About This Department
Medical oncology
One breast cancer in five or six carries too much of a protein called HER2, and before 1998 that made it one of the worst kinds to have. Trastuzumab turned it into one of the most treatable. The test comes first. The drug follows.
Trastuzumab, sold under the brand name Herceptin and now also as several biosimilars, is an antibody that attaches to HER2 on cancer cells, blocks the growth signal it sends, and marks the cells for destruction by the immune system. It works only in tumors that overexpress HER2, which a pathology test confirms. Added to chemotherapy after surgery for early breast cancer, it raised ten-year survival from 75.2 to 84 percent in more than 4,000 women (Perez and colleagues, Journal of Clinical Oncology, 2014). Six months of treatment proved as effective as twelve in a British trial of 4,088 patients, with fewer patients stopping for heart problems (Earl and colleagues, Lancet, 2019). In HER2-positive stomach cancer it extended median survival from 11.1 to 13.8 months (Bang and colleagues, Lancet, 2010). This page explains what trastuzumab is, how HER2 is tested, where the drug is used and with what, how it is given, what the trials show, its effect on the heart, biosimilars, and how patients from abroad arrange treatment at Biruni Hospital in Istanbul.
84
Percent alive at ten years after chemotherapy plus trastuzumab for HER2-positive early breast cancer, against 75.2 percent without
89.4
Percent free of disease at four years after six months of trastuzumab, against 89.8 percent after twelve
13.8
Months median survival with trastuzumab plus chemotherapy in HER2-positive stomach cancer, against 11.1 months
Free
Review of your pathology, HER2 result and heart scan by the medical oncology team
HER2 is a receptor on the surface of cells that tells them to grow. Normal breast cells carry a modest number. In HER2-positive cancers a gene fault multiplies the receptor many times over, the growth signal never stops, and the cancer grows fast and spreads early. Trastuzumab is a humanized antibody that binds HER2, blocks the signal, and flags the cancer cell for the immune system to kill.
Regulators approved it in 1998 for HER2-positive breast cancer that had spread, and from 2005 onward four large trials showed that adding it to chemotherapy after surgery cut recurrences by half. A diagnosis that had carried one of the worst outlooks in breast cancer became one with one of the best. Quickly. Within a decade. The same principle later extended to stomach cancer, and a family of newer HER2 drugs grew from it.
One name, several products
Is Herceptin the same as trastuzumab?
Yes. Herceptin is the brand name of the original product, and trastuzumab is the international name of the molecule. Since 2017 several biosimilars, copies approved after showing the same effect in trials, have been sold under other names. The hospital prescribes under the international name and records which product was given.
Adding trastuzumab to chemotherapy led to a 37 percent relative improvement in overall survival and an increase in ten-year survival from 75.2 percent to 84 percent. All patient subgroups benefited (Perez and colleagues, 2014).
HER2 testing
No test, no trastuzumab.
Trastuzumab does nothing for a tumor without HER2 overexpression, and a wrong result either denies a patient an effective drug or exposes her to one that cannot help.
Two tests on the same tissue
Immunohistochemistry stains the HER2 protein on the tumor cells and scores it from 0 to 3+. In situ hybridization, FISH or its variants, counts the copies of the HER2 gene. A score of 3+ is positive. A score of 2+ is equivocal and goes to in situ hybridization to decide. A score of 0 or 1+ is negative for trastuzumab.
Reading a HER2 result
Result
Meaning
Consequence
IHC 3+
Strong, complete staining in more than 10 percent of cells
HER2-positive, trastuzumab indicated
IHC 2+ with amplified ISH
Borderline protein, gene copies raised
HER2-positive, trastuzumab indicated
IHC 2+ with non-amplified ISH
Borderline protein, gene normal
HER2-negative for trastuzumab, HER2-low
IHC 1+
Faint, incomplete staining
HER2-negative for trastuzumab, HER2-low
IHC 0
No staining
HER2-negative
HER2-low
New since 2022.
A category that did not exist before then. Tumors scoring 1+ or 2+ without amplification do not respond to trastuzumab, but when they have spread they respond to trastuzumab deruxtecan, a newer drug that carries chemotherapy into any cell with some HER2 on its surface. The result that once read simply negative now needs its exact score, and a patient whose report says only HER2-negative should ask for the number. In stomach cancer the scoring rules differ slightly, and the pathologist uses the gastric criteria.
Where it is used
HER2-positive breast cancer at every stage, and HER2-positive cancer of the stomach and the junction with the esophagus when it has spread. Those are the approved uses. Other cancers with HER2 amplification, in the bowel, the bladder, the uterus and the salivary glands, have responded in smaller studies, and the decision there is made case by case.
1
Early breast cancer
Before surgery with chemotherapy and usually pertuzumab, to shrink the tumor and test its sensitivity, then after surgery to complete a year in total. Or after surgery alone for small tumors, with a lighter chemotherapy partner.
2
Breast cancer that has spread
With pertuzumab and a taxane as the first treatment, continued as long as the cancer stays controlled, often for years.
3
Stomach cancer that has spread
With platinum and fluoropyrimidine chemotherapy as the first treatment, in the one patient in five whose tumor is HER2-positive.
Where it does not help
HER2-negative breast cancer, including HER2-low, where trastuzumab alone adds nothing. And early stomach cancer before or after surgery, where trials of HER2 drugs have not shown a survival gain, so that the drug is reserved for disease that has spread. Knowing where a drug fails matters as much.
How it is given
Every three weeks, into a vein or under the skin, for a fixed course in early disease and for as long as it works in spread disease.
How long does treatment last?
A year in total for early breast cancer, the standard since the first trials. PERSEPHONE randomized 4,088 patients to six or twelve months and found four-year disease-free survival of 89.4 percent against 89.8 percent, which met the test for noninferiority, with fewer serious side effects and fewer patients stopping for heart problems, 3 percent against 8 percent (Earl and colleagues, 2019). Six months is now offered to selected patients at similar risk, above all those whose heart function has dipped. For spread disease there is no fixed end, and treatment continues while the cancer stays controlled.
Into a vein, first dose. 8 milligrams per kilogram over ninety minutes, with observation for infusion reactions.
Into a vein, later doses. 6 milligrams per kilogram over thirty minutes every three weeks.
Under the skin. A fixed 600 milligrams into the thigh over about five minutes every three weeks, regardless of weight.
The subcutaneous form was tested against the infusion in the HannaH trial of 596 patients before surgery. Blood levels were higher with the injection, and the rate of complete disappearance of cancer in the removed breast was 45.4 percent against 40.7 percent, which met the test for noninferiority (Ismael and colleagues, Lancet Oncology, 2012). Patients who prefer a short visit and have no reason to need the weight-based dose can choose it.
1
Pregnancy
Trastuzumab harms the developing kidneys of a fetus and reduces the fluid around it, and it is not given during pregnancy. Women of childbearing age use reliable contraception during treatment and for seven months after the last dose.
Partner drugs
Drugs given with or after trastuzumab
Drug
What it adds
When it is used
Chemotherapy, a taxane or a platinum doublet
Kills dividing cells, and trastuzumab works better alongside it
Every setting, with the partner chosen by stage
Pertuzumab
A second HER2 antibody binding a different part of the receptor, so the two block the signal more completely
Before surgery for larger or node-positive tumors, and first treatment for spread disease
Trastuzumab emtansine
Trastuzumab joined to a chemotherapy that it carries into HER2-positive cells
After surgery when cancer remains despite treatment before it, and later lines for spread disease
Trastuzumab deruxtecan
A newer carrier with a more potent payload, active even in HER2-low tumors
Spread disease after earlier HER2 treatment, and HER2-low spread disease
Hormone therapy
Blocks estrogen in tumors that carry both receptors
Alongside or after trastuzumab in hormone-positive, HER2-positive cancer
The choice after surgery
1
When treatment before surgery clears the cancer
Trastuzumab, with or without pertuzumab, completes the year. The outlook is excellent.
2
When cancer remains in the removed tissue
Trastuzumab emtansine replaces trastuzumab for the rest of the year, since residual disease marks a higher risk and the carrier drug lowers it.
What the trials show
Two American trials, analyzed together. 4,046 women with operable HER2-positive breast cancer, followed for a median of 8.4 years, of whom those given trastuzumab with their chemotherapy had a 40 percent lower risk of recurrence and a 37 percent lower risk of death. At ten years, 84 percent were alive against 75.2 percent, and 73.7 percent were free of disease against 62.2 percent (Perez and colleagues, 2014).
Those numbers came from women treated in the early 2000s. Pertuzumab and the carrier drugs did not yet exist. A woman diagnosed today with the same cancer receives more and better HER2 treatment than anyone in those trials, and her outlook is better still.
Four trials in summary
Key trials of trastuzumab
Trial
Patients
Finding
NSABP B-31 and NCCTG N9831, 2014
4,046 with early breast cancer
Ten-year survival 84 against 75.2 percent
PERSEPHONE, 2019
4,088 with early breast cancer
Six months as effective as twelve, with less heart toxicity
HannaH, 2012
596 treated before surgery
Injection under the skin as effective as the infusion
ToGA, 2010
594 with spread stomach or junction cancer
Median survival 13.8 against 11.1 months, with no increase in serious side effects or heart events
The heart
The side effect that matters. The others, chills and fever with the first infusion, tiredness and diarrhea, stay mild, and none of them has ever been the reason a patient in the large trials stopped the drug in any number, which is the reason the heart gets its own section and the rest get a sentence.
1
What happens
HER2 also helps heart muscle cells cope with stress. Blocking it can weaken the pumping of the heart, measured as a fall in the ejection fraction, the share of blood the left ventricle pushes out with each beat. It causes symptoms of heart failure in a small minority, and a silent fall on the scan in more.
Will my heart recover?
In nearly all patients, yes. Unlike the heart damage from anthracycline chemotherapy, which is permanent, the weakening from trastuzumab reverses when the drug is paused, over weeks to months, and most patients restart and complete their course once the scan has recovered. The risk is higher after anthracyclines, above 65, with high blood pressure or existing heart disease, and these patients are watched more closely.
Monitoring
An echocardiogram or a nuclear heart scan before the first dose, as the baseline.
The same scan every three months during treatment, and sooner for breathlessness, ankle swelling or palpitations.
A pause and a cardiology review if the ejection fraction falls by ten points or below 50 percent, with medicines to support the heart and a repeat scan before restarting.
In PERSEPHONE, 8 percent of patients stopped trastuzumab early because of heart problems on twelve months against 3 percent on six months (Earl and colleagues, 2019). Shorter treatment spares the heart, and for patients whose heart scan dips, that trade is worth discussing.
Biosimilars
1
What a biosimilar is
A copy of an antibody made by another company once the original patent has expired, approved only after trials show the same blood levels, the same effect and the same side effects. Several trastuzumab biosimilars have been approved in Europe and the United States since 2017.
Switching and choosing
Are biosimilars as good as Herceptin?
For the patients studied, yes. Each biosimilar went through a randomized trial against the original, most of them in the setting before surgery where the rate of complete response is a sensitive measure, and none showed a meaningful difference. Regulators allow a biosimilar for every approved use of the original. The practical difference lies in price and availability, and a patient may receive a biosimilar in one country and the original in another without any loss.
The hospital records the product and the batch for every dose, so that a patient who continues treatment at home can show exactly what was given.
Biosimilars exist only for intravenous trastuzumab. The subcutaneous form, where available, is the original product.
Treatment for patients from abroad
Trastuzumab runs for a year in early breast cancer and indefinitely in spread disease, so patients from abroad come in one of three ways. For surgery and the treatment around it, starting with chemotherapy and HER2 drugs before the operation, a length of stay of four to six months in total, taken in blocks with breaks at home. For a start here, the first cycles, the HER2 testing if needed and the heart scan, then continuation at home on the same protocol. Or for a second opinion on the pathology and the plan, with treatment at home. What the team needs is the pathology report with the HER2 score and, if possible, the blocks, the staging scans as image files, the list of medicines, any previous chemotherapy with doses, and a recent heart scan. The medical oncology team reviews the file without charge and replies with the plan and the cost.
Arrangements
One coordinator from the international patients office handles arrangements from the first message through discharge and answers the same WhatsApp number once you are back home. The office works in English, Arabic, French, Russian, Serbian, Romanian and Spanish and books interpreters for other languages, and it arranges the visa invitation letter, airport transfers, daily transport and accommodation near the hospital. Halal, vegetarian and diabetic meals, a prayer room on site, and a female physician on request wherever the rota allows.
1
Fitness to fly
The day after a dose of trastuzumab alone. After chemotherapy cycles the oncologist sets the date according to the blood count, a week after the cycle for most.
A year of treatment
Long. Light.
For most women the hard part of HER2-positive breast cancer treatment comes in the first four to six months, when chemotherapy runs alongside the antibodies and the hair, the blood counts and the energy all suffer. After surgery the chemotherapy has finished for the great majority, and what remains is trastuzumab every three weeks, sometimes with pertuzumab, for the rest of the year. Hair grows back. Work resumes. Most women return to travel and exercise too, and the three-weekly visit becomes a routine of a blood test, a short consultation and a half-hour infusion or a five-minute injection. The heart scan every three months punctuates the year, and a dip on the scan is the one thing that interrupts it, for a few weeks at most in nearly every case. Patients who live abroad can complete this second half of the year at home, since the drug, the dose and the monitoring are the same everywhere, and the oncologist here reviews each heart scan and answers questions from the oncologist there.
Care continues past the last dose. Hormone therapy continues for years in tumors that carry both receptors, a mammogram follows every year, and a patient who stays well for five years has, as a rule, left the cancer behind. That goal, most reach.
Cost
One figure per cycle, after the file review.
What a quote for trastuzumab covers
Item
Usually included
Priced separately
The drug
Dose for the cycle, original or biosimilar, infusion or injection
HER2 testing, heart scans every three months, staging scans
1
Comparing quotes
Biosimilar and original prices differ, and weight-based and fixed doses differ. Compare quotes for the same product, the same route and the same inclusions, and ask whether the heart scans are part of the figure.
References
Perez EA, Romond EH, Suman VJ, 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 Clin Oncol. 2014;32(33):3744-3752.
Earl HM, Hiller L, Vallier AL, et al. 6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE). 4-year disease-free survival results of a randomized phase 3 non-inferiority trial. Lancet. 2019;393(10191):2599-2612.
Ismael G, Hegg R, Muehlbauer S, et al. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study). A phase 3, open-label, multicentre, randomized trial. Lancet Oncol. 2012;13(9):869-878.
Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-esophageal junction cancer (ToGA). A phase 3, open-label, randomized controlled trial. Lancet. 2010;376(9742):687-697.
Editor's note
Written by the Biruni Hospital medical editorial team. Reviewed by Prof. Dr. Özcan YILDIZ, Medical Oncology.
