Trastuzumab (Herceptin)
- Medical Review: Debu Tripathy, MD
Trastuzumab is a targeted therapy known as a monoclonal antibody, a modified version of an immune system protein, that can target proteins on HER2-positive breast cancer cells and stop them from growing. Herceptin is the brand name for trastuzumab, the most common medicine used to treat HER2-positive breast cancer.
Trastuzumab is a biologic drug made from cells that have been engineered to express a humanized antibody that binds to the HER2 protein, interfering with cancer cell growth. Generic versions of trastuzumab, called biosimilars, are also available and can be used in place of trastuzumab. Biosimilars have nearly — but not exactly — the same chemical makeup as biologic drugs and work in a similar way. Biosimilar versions of trastuzumab can be less expensive than trastuzumab but equally effective.
Research shows people with HER2-positive breast cancer treated with trastuzumab, along with chemotherapy, are likely to live longer than those with HER2-positive disease who receive chemotherapy alone. In early-stage breast cancer, treatment with trastuzumab and chemotherapy also cuts the risk of recurrence (cancer coming back) by one-third.
How trastuzumab works
In HER2-positive breast cancer, high levels of a protein called HER2, or human epidermal growth factor receptor 2, trigger breast cancer cells to grow and multiply. The HER2 gene makes HER2 proteins, which are receptors found on the outside of all healthy breast cells and receive signals that tell the cells to grow. When the HER2 gene is amplified (multiple copies of the gene) or otherwise expressed at high levels, it creates too many HER2 receptors — and therefore too many growth signals — which can lead to the development of breast cancer.
Trastuzumab works by attaching to the HER2 receptors on the outside of the cancer cells and blocking the signals that tell the cells to keep growing and multiplying. It may also activate the immune system against the HER2 protein and HER2-expressing breast cancer cells.
Who gets trastuzumab?
Trastuzumab is a standard treatment for people diagnosed with early-stage or metastatic HER2-positive breast cancer. In early-stage breast cancer, trastuzumab works to reduce the risk of the cancer coming back. In metastatic breast cancer, it works to slow the cancer’s growth.
If the breast cancer is both hormone receptor-positive and HER2-positive, you are likely to receive targeted treatments for both types of breast cancer.
How trastuzumab is given
Trastuzumab can be given by vein through an IV, or by injection:
- Trastuzumab given by IV uses a needle or a port to drip medicine directly into a vein in a process called infusion. The first infusion may last 90 minutes or longer, after which infusions usually take around 30 minutes. The dose is based on how much you weigh.
- Trastuzumab and hyaluronidase-oysk, the type of trastuzumab given by injection (brand name: Herceptin Hylecta), is delivered by inserting a needle under the skin (subcutaneously), usually in the thigh, without needing to access a vein. It takes about five minutes. The dose does not change based on your weight.
Trastuzumab for early-stage breast cancer
In early-stage breast cancer, trastuzumab or trastuzumab and hyaluronidase-oysk can be given with chemotherapy at the start of treatment and then may be given alone for an extended period (often called maintenance treatment). It is typically given every three weeks.
Trastuzumab can be given before (neoadjuvant treatment) or after (adjuvant treatment) surgery.
Trastuzumab before surgery: When given before surgery in early breast cancer (called neoadjuvant treatment), trastuzumab and chemotherapy given with it help to shrink large tumors.
- In some cases, neoadjuvant treatment makes it possible to have a lumpectomy instead of a mastectomy.
- Neoadjuvant treatment is becoming the preferred approach for early-stage, HER2-positive larger tumors (more than 2-3 centimeters), or if there is cancer in any underarm (axillary) lymph nodes in addition to a tumor. This is because recently, a study showed that if there is still invasive disease left after receiving chemotherapy and trastuzumab before surgery, ado-trastuzumab emtansine (Kadcyla) is more effective than trastuzumab when taken for one year after surgery.
Trastuzumab after surgery: If trastuzumab is used after surgery (adjuvant treatment), it is given for one year.
If the cancer has a high risk of recurrence, pertuzumab (Perjeta), another HER2-targeting treatment, can be added to trastuzumab treatment either before or after surgery.
Trastuzumab treatment combinations in early-stage breast cancer
Here are some trastuzumab treatment combinations used to treat early-stage breast cancer:
- TCHP: paclitaxel, carboplatin, trastuzumab, and pertuzumab for stage I and II breast cancer that has a high risk of recurrence
- APT: adjuvant paclitaxel plus trastuzumab for small (up to 3 centimeters), HER2-positive, node-negative breast cancers; this use of less treatment is known as de-escalated treatment
- ACTH: Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide) followed by paclitaxel (Taxol) and trastuzumab (not used as often as in the past due to heart health concerns)
- TCH: docetaxel (Taxotere) or paclitaxel (Taxol), carboplatin, and trastuzumab (this is an older combination not used as often anymore due to the approval of pertuzumab)
Trastuzumab timing in early-stage breast cancer
Trastuzumab is typically given every three weeks. It can be given at the same time as chemotherapy or after chemo is complete. Here are some timing examples:
- In the TCHP regimen mentioned above, chemotherapy, trastuzumab, and pertuzumab are all given at the same time.
- A different plan may involve receiving some of the chemotherapy drugs mentioned above without trastuzumab for several cycles, followed by taxane chemotherapy (either docetaxel or paclitaxel) along with trastuzumab. When taxane treatment is complete, trastuzumab is given until about a year of treatment is complete.
- In another regimen, all the chemotherapy treatment is given first, followed by trastuzumab.
If you are discussing these plans with your care team, ask if one plan may be better for your situation than another, and why.
Trastuzumab for metastatic breast cancer
In metastatic breast cancer, trastuzumab can be given alone on an ongoing basis or with pertuzumab and chemotherapy.
The standard first treatment with trastuzumab in metastatic breast cancer is called THP: a combination of docetaxel, trastuzumab, and pertuzumab.
Talk with your team about what treatments and combinations they recommend, and why a certain regimen may be recommended over others.
Phesgo, a trastuzumab-containing treatment (any stage)
Another treatment that includes trastuzumab is Phesgo, a combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf. This treatment is available as an injection for people diagnosed with HER2-positive breast cancer of any stage (early, locally advanced, or metastatic).
Phesgo can also be used to treat HER2-positive inflammatory breast cancer.
The first dose of Phesgo is injected under the skin over about eight minutes. Future doses are given every three weeks over five minutes.
- In early breast cancer, if given before surgery, Phesgo is injected every three weeks, with chemotherapy given by vein for three to six cycles.
- In early breast cancer, if given after surgery, Phesgo is injected every three weeks, with up to 18 cycles of chemotherapy given over one year.
- In metastatic breast cancer, Phesgo and the chemotherapy docetaxel are given every three weeks.
Treatment | Used to treat | Initial dose | Following doses |
Trastuzumab | Early-stage and metastatic HER2-positive breast cancer | IV given over 90 minutes | IV given over 30 minutes |
Trastuzumab and hyaluronidase-oysk | Early-stage and metastatic HER2-positive breast cancer | Injection given over five minutes | Injection given over 2-5 minutes |
Phesgo | Early-stage and metastatic HER2-positive breast cancer | Injection given over eight minutes | Injection given over five minutes |
Trastuzumab Biosimilars
Biosimilars of trastuzumab are also FDA-approved to treat HER2-positive breast cancer. While these drugs are not exact copies of trastuzumab, they are highly similar in structure and function. They may cost less, and they are just as effective.
Trastuzumab biosimilars are given as an IV infusion, the same way trastuzumab is given. The trastuzumab biosimilars below are approved to treat all stages of HER2-positive breast cancer:
- Trastuzumab-anns (Kanjinti)
- Trastuzumab-dkst (Ogivri)
- Trastuzumab-dttb (Ontruzant)
- Trastuzumab-qyyp (Trazimera)
- Trastuzumab-pkrb (Herzuma)
- Trastuzumab-strf (Hercessi)
Trastuzumab side effects
In general, trastuzumab is less likely than chemotherapy to cause serious side effects that could make you need to stop treatment.
While most people experience mild side effects, the FDA does include a boxed warning on the prescription package inserts for trastuzumab, trastuzumab and hyaluronidase-oysk, and Phesgo. Boxed warnings are used to highlight the most severe possible side effects of a medicine and can be found within a bold, black box on the insert.
Always let your care team know about the side effects you experience, whether they are mild or severe. Many mild side effects can be managed with medicine or other therapies. Your doctors will monitor you for severe side effects, but if you think you’re experiencing heart or lung issues, seek emergency care.
The most common mild side effects of trastuzumab include:
- Fever or chills
- Muscle aches
- Nausea
- Skin reaction to injection, including redness and irritation
- Low white blood cell count, which can lead to infections
- Diarrhea
- Skin rash
- Itching skin
- Runny nose
The box warnings differ slightly between trastuzumab, trastuzumab and hyaluronidase-oysk, and Phesgo. These rare but severe side effects include:
Trastuzumab:
- Allergic reaction
- Lung inflammation
Some people experience heart side effects such as weakness of the heart muscle, known as cardiomyopathy, due to trastuzumab. This is monitored using tests that image the heart: either an echocardiogram or a multigated angiogram (MUGA scan). These tests are performed before starting treatment to make sure there are no underlying heart issues. After that, the tests are done about every three months. Decreases in heart function usually recover after stopping trastuzumab.
Trastuzumab and hyaluronidase-oysk:
- Heart problems
- Allergic reaction
- Lung inflammation
Phesgo:
- Heart problems
- Birth defects and miscarriage, if given during pregnancy
- Allergic reaction
- Lung inflammation
You should not take trastuzumab if you are pregnant. You can read more about heart, lung, pregnancy, and breastfeeding risks in the sections below.
Before starting trastuzumab, tell your doctor about any medicines you are taking, including vitamins, herbal supplements, and over-the-counter medicines.
Your doctor, pharmacist, or nurse can help you manage side effects. You can also visit our section on side effects for more information.
Trastuzumab and alcohol use
Having an occasional alcoholic drink while taking trastuzumab is OK for most people. However, heavy drinking can increase the risk of heart problems because it raises your blood pressure.
Trastuzumab and pregnancy or breastfeeding
Trastuzumab can harm a developing fetus and may cause miscarriage. Doctors do not recommend treatment with trastuzumab if you’re pregnant. If you recently gave birth and plan to breastfeed, know that there is little research on the safety of taking trastuzumab while nursing. Right now, the medicine’s manufacturer recommends not taking trastuzumab while you breastfeed and avoiding breastfeeding for seven months after ending treatment with trastuzumab.
Trastuzumab and heart problems
If you had a history of heart issues before being diagnosed with breast cancer, trastuzumab may not be an option for you, because it can lead to heart failure. If you have a known heart issue, talk to your doctor about other cancer treatments that are safe and available to you.
The idea of heart issues can be scary, but research shows most heart problems caused by trastuzumab are not permanent or long-term. Though it’s unlikely you’ll have serious heart problems while taking trastuzumab, it’s important that your doctor closely monitor your heart health while you take this medicine.
Before you start trastuzumab and throughout treatment, your healthcare team will monitor your heart health using a test called an echocardiogram (sometimes called an echo). If your first echo suggests you have heart problems, trastuzumab may not be the right treatment for you. Talk with your healthcare team about other options.
Trastuzumab and lung issues
Although rare, trastuzumab can cause serious lung problems. Lung issues can include shortness of breath, fluid buildup in the lungs, and inflammation of the lungs. If you have a history of lung issues, let your healthcare team know before starting trastuzumab.
Other HER2-targeting therapies
Targeted therapies are treatments that target specific parts of cancer cells that help the cells to grow and multiply. There are many targeted therapies available to treat HER2-positive breast cancer. They include:
Monoclonal antibodies:
- Trastuzumab and its biosimilars
- Pertuzumab (Perjeta)
- Margetuximab (Margenza)
Antibody-drug conjugates:
- Ado-trastuzumab emtansine (Kadcyla)
- Trastuzumab deruxtecan (Enhertu)
Tyrosine kinase inhibitors (TKIs):
Trastuzumab FAQs
How much does Herceptin cost? Is it covered by insurance?
In the United States, insurance coverage of prescription medications varies widely. Some plans may cover significant portions of the cost of treatments, while other plans may cover very little.
For biosimilar versions of trastuzumab, individual insurance companies can determine which ones will be covered and which won’t. The best way to find out if your insurance plan covers trastuzumab (completely or partially) is to call your insurance provider and ask for a list of covered drugs, sometimes called a formulary.
Trastuzumab’s manufacturer, Genentech, offers some financial assistance programs to help make the medicine more affordable. You can find out more about their programs here.
Why is trastuzumab given every three weeks?
Trastuzumab can be given weekly with chemotherapy, or, if given after surgery, can be given every three weeks or every week (at one-third of the dose given every three weeks). Your doctors will decide which schedule to use, and it’s OK to ask why. Know that both schedules have been shown to work equally well.
How long do trastuzumab side effects last?
Each person taking trastuzumab will have their own individual experience of side effects, including how long they last. Talk with your doctor about your unique health history and what to expect with trastuzumab. You may also want to keep a daily log of any side effects you experience to share with your healthcare team. If you experience side effects that interfere with your daily activities or quality of life, your team can help you find ways to manage them.
How long does trastuzumab stay in your system?
Research has shown that trastuzumab can take up to 18 weeks to completely leave the body.
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- noninvasive
- nonmalignant
- nonmetastatic
- nonprescription
- nonrandomized clinical trial
- nonsteroidal anti-inflammatory drug
- nonsteroidal aromatase inhibitor
- nontoxic
- normal range
- normative
- NP
- NPO
- NSAID
- nuclear grade
- nuclear magnetic resonance imaging
- nuclear medicine scan
- nurse
- nurse practitioner
- nutrition
- nutrition therapy
- nutritional counseling
- nutritional status
- nutritional supplement
- nutritionist
- obese
- objective improvement
- objective response
- observation
- observational study
- obstruction
- off-label
- olaparib
- oncologist
- oncology
- oncology nurse
- oncology pharmacy specialist
- oncolysis
- ondansetron
- onset of action
- oophorectomy
- open biopsy
- open label study
- open resection
- operable
- opiate
- opioid
- opportunistic infection
- oral
- organ
- orthodox medicine
- osteolytic
- osteonecrosis of the jaw
- osteopenia
- osteoporosis
- OTC
- out of network
- outcome
- outpatient
- ovarian
- ovarian ablation
- ovarian cancer
- ovarian suppression
- ovary
- over-the-counter
- overall survival rate
- overdose
- overexpress
- overweight
- ovulation
- PA
- paclitaxel
- paclitaxel albumin-stabilized nanoparticle formulation
- paclitaxel-loaded polymeric micelle
- Paget disease of the nipple
- pain threshold
- palliation
- palliative care
- palliative therapy
- palmar-plantar erythrodysesthesia
- palonosetron hydrochloride
- palpable disease
- palpation
- palpitation
- pamidronate
- panic
- papillary tumor
- Paraplatin
- parenteral nutrition
- paroxetine hydrochloride
- PARP
- PARP inhibitor
- partial-breast irradiation
- partial mastectomy
- partial oophorectomy
- partial remission or partial response
- pastoral counselor
- paternal
- pathologic fracture
- pathological stage
- pathological staging
- pathologist
- pathology report
- patient advocate
- Paxil
- peau d'orange
- pedigree
- peer-review process
- peer-reviewed scientific journal
- perfusion magnetic resonance imaging
- perimenopausal
- periodic neutropenia
- perioperative
- peripheral neuropathy
- peripheral venous catheter
- personal health record
- personal medical history
- personalized medicine
- Pertuzumab
- PET scan
- pharmacist
- phase I/II trial
- phase I trial
- phase II/III trial
- phase II trial
- phase III trial
- phase IV trial
- phlebotomy
- photon beam radiation therapy
- phyllodes tumor
- physical examination
- physical therapist
- physical therapy
- physician
- physician assistant
- physiologic
- PI3 kinase inhibitor
- pilocarpine
- pilot study
- placebo
- placebo-controlled
- plastic surgeon
- plastic surgery
- population study
- positive axillary lymph node
- positive test result
- positron emission tomography scan
- post-traumatic stress disorder
- postmenopausal
- postoperative
- postremission therapy
- potentiation
- power of attorney
- PR
- PR+
- PR-
- practitioner
- preauthorization
- precancerous
- preclinical study
- predictive factor
- pregabalin
- premalignant
- premature menopause
- premenopausal
- premium
- prescription
- prevention
- preventive
- preventive mastectomy
- primary care
- primary care doctor
- primary endpoint
- primary therapy
- primary treatment
- primary tumor
- Principal investigator
- prochlorperazine
- progesterone
- progesterone receptor
- progesterone receptor-negative
- progesterone receptor-positive
- progesterone receptor test
- progestin
- prognosis
- prognostic factor
- progression
- progression-free survival
- progressive disease
- Prolia
- proliferative index
- promegapoietin
- prophylactic
- prophylactic mastectomy
- prophylactic oophorectomy
- prophylactic surgery
- prophylaxis
- prospective
- prospective cohort study
- prosthesis
- protective factor
- protein
- protein-bound paclitaxel
- protein expression
- protein expression profile
- protocol
- proton
- proton magnetic resonance spectroscopic imaging
- pruritus
- psychiatrist
- psychological
- psychologist
- psychosocial
- psychotherapy
- PTSD
- pump
- punch biopsy
- qi
- qigong
- quadrantectomy
- quality assurance
- quality of life
- radiation
- radiation brachytherapy
- radiation dermatitis
- radiation fibrosis
- radiation necrosis
- radiation nurse
- radiation oncologist
- radiation physicist
- radiation surgery
- radiation therapist
- radiation therapy
- radical lymph node dissection
- radical mastectomy
- radioactive
- radioactive drug
- radioactive seed
- radioisotope
- radiologic exam
- radiologist
- radiology
- radionuclide
- radionuclide scanning
- radiopharmaceutical
- radiosensitization
- radiosensitizer
- radiosurgery
- radiotherapy
- raloxifene
- raloxifene hydrochloride
- randomization
- randomized clinical trial
- receptor
- RECIST
- reconstructive surgeon
- reconstructive surgery
- recreational therapy
- recurrence
- recurrent cancer
- referral
- reflexology
- refractory
- refractory cancer
- regimen
- regional
- regional anesthesia
- regional cancer
- regional chemotherapy
- regional lymph node
- regional lymph node dissection
- registered dietician
- regression
- rehabilitation
- rehabilitation specialist
- relapse
- relative survival rate
- relaxation technique
- remission
- remission induction therapy
- remote brachytherapy
- research nurse
- research study
- resectable
- resected
- resection
- residual disease
- resistant cancer
- resorption
- respite care
- response rate
- retrospective cohort study
- retrospective study
- risk factor
- Rubex
- salpingo-oophorectomy
- salvage therapy
- samarium 153
- sargramostim
- scalpel
- scan
- scanner
- scintigraphy
- scintimammography
- sclerosing adenosis
- screening
- screening mammogram
- second-line therapy
- second-look surgery
- second primary cancer
- secondary cancer