Trastuzumab Therapy - Herceptin

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.

What trastuzumab is

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

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.

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

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.

1. Into a vein, first dose. 8 milligrams per kilogram over ninety minutes, with observation for infusion reactions.
2. Into a vein, later doses. 6 milligrams per kilogram over thirty minutes every three weeks.
3. Under the skin. A fixed 600 milligrams into the thigh over about five minutes every three weeks, regardless of weight.

Partner drugs

The choice after surgery

What the trials show

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

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.

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

Switching and choosing

Biosimilars exist only for intravenous trastuzumab. The subcutaneous form, where available, is the original product.

Treatment for patients from abroad

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.

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.