Ms. A was diagnosed with HER-2 positive breast cancer after an unintentional finding of a mass in her left breast and armpit, and Dr. B recommended targeted therapy.
What are the options for targeted therapy?
Targeted therapy is a treatment that uses drugs that bind to tumor-specific targets to specifically kill tumor cells while protecting surrounding normal tissue cells as much as possible. These patients account for about 15% to 30% of breast cancers and often have poor outcomes. Anti-HER-2 targeted drugs can specifically treat HER-2-positive invasive breast cancer and include monoclonal antibody classes (trastuzumab, patuximab, T-DM1) and small molecule inhibitor classes (lapatinib).
- Trastuzumab is indicated for postoperative adjuvant therapy and can also be used alone or in combination with paclitaxel and docetaxel in advanced breast cancer.
- The dual-targeted combination chemotherapy regimen of patuximab with trastuzumab and docetaxel is recommended as the standard of care for HER-2-positive advanced breast cancer that was once treated with surgery only, to slow progression. Dual-targeted therapy may also be used as preoperative neoadjuvant therapy in HER-2-positive, locally advanced, inflammatory, or early-stage breast cancer.
- T-DM1 combines trastuzumab with a chemotherapy drug given intravenously every 3 weeks to treat advanced breast cancer that has received trastuzumab and chemotherapy, and to slow progression.
- Lapatinib is an oral agent that can be used in advanced breast cancer, and may be effective when changed to lapatinib after resistance to trastuzumab therapy.
What are the adverse effects of targeted therapy and how are they managed?
Cardiac toxicity
It may cause palpitations, shortness of breath, arrhythmias, and in severe cases, heart failure. Before treatment, the physician will take a complete medical history, paying special attention to the presence of underlying cardiac disease, perform a physical examination, and complete an electrocardiogram and echocardiogram left ventricular ejection fraction (LVEF) assessment. During treatment, the infusion rate is usually slowed down and continuous cardiac monitoring is performed until the targeted drug infusion is completed. Cardiac function is generally monitored regularly during drug administration, and treatment doses may also be reduced or even permanently discontinued at the physician’s discretion if impaired cardiac function occurs.
Infusion-related reactions
Infusion reactions occur in about 40% of first-time users and usually occur during the infusion or within 24 hours of treatment, and are usually slowed or temporarily interrupted by the physician. During treatment, it is important to monitor changes in vital signs. Those with fever should rest in bed, drink plenty of fluids, keep warm, and take antipyretic or antiallergic medications to relieve symptoms. If respiratory distress or a significant decrease in blood pressure occurs, the doctor will stop the targeted therapy and treat the symptoms, and continue to observe until the symptoms disappear completely.
Diarrhea
We recommend adjusting the diet, paying attention to dietary cleanliness and hygiene, avoiding cold, greasy, gas-producing foods, and advocating a light, easily digestible, less residue, low-fiber diet with fewer meals and hydration. If the diarrhea is severe, the doctor will consider suspending the targeted drugs or lowering the dose appropriately, while treating with antidiarrheal medication.
Rash
Some patients may develop a rash after dosing, which can usually be continued with targeted therapy. The doctor may recommend corticosteroid ointment, for example, for the rash, or antibiotics for co-infection. If the rash continues to worsen or does not improve significantly, your doctor may consider suspending targeted therapy or discontinuing it.
Hepatotoxicity
Manifesting as a temporary elevation in serum transaminases, physicians will test liver function before starting treatment and before each dose, and targeted drugs are generally not recommended for patients with active hepatitis B or C. The physician will usually permanently discontinue treatment if serum aminotransferases are elevated more than 3 times normal and total bilirubin is elevated more than 2 times normal.
Thrombocytopenia
Test platelets before starting treatment and before each dose. If the platelet count is low, the doctor will suspend treatment and continue at the original dose after the platelets have recovered to a certain level. If platelets are too low, treatment will usually be suspended and continued at the appropriate reduced dose after platelets have recovered to a certain level. Because of the risk of bleeding, care should be taken to prevent falls and bed falls. It is advisable to eat a cold-leaning diet and keep the bowels open.
Pulmonary toxicity
Doctors will stop treatment if interstitial pneumonia or acute respiratory distress syndrome occurs.
What to look for when neoadjuvant targeted therapy?
Because Ms. A has a large breast mass and she wants the opportunity to preserve her breast, Dr. B suggests neoadjuvant therapy first to help shrink the tumor, create an opportunity for surgery or breast conservation, and to see how effective the treatment plan is.
The doctor advised that neoadjuvant targeted therapy is not acceptable if the following conditions exist:
- unconfirmed by biopsy;
- In early pregnancy;
- Ageing and frail with severe heart disease that is not expected to be tolerated;
- In the middle to late stages of pregnancy, also with caution.
Before neoadjuvant targeted therapy, doctors advise the following preparations are needed.
- Physical examination and imaging to assess the status of the pre-treatment lesion as a reference for subsequent assessment of efficacy;
- Biopsy of the primary lesion to obtain a basis for treatment;
- exclusion of pregnancy and contraception;
- Check cardiac function;
- understand treatment-related adverse effects and sign an informed consent form.
For neoadjuvant targeted therapy regimens, Dr. B recommended trastuzumab in combination with chemotherapy, and the chemotherapy regimen suggested by the physician could be anthracycline sequenced with paclitaxel, paclitaxel plus carboplatin, etc.
What to use for adjuvant targeted therapy?
Ms. A had neoadjuvant targeted therapy to reduce the size of her lump and had breast cancer surgery to remove a tumor larger than 1.0 cm in diameter, and her postoperative biopsy was still positive for HER-2. Dr. B recommended continued targeted therapy after surgery to help control the disease, reduce the risk of recurrence, and improve the cure rate, but cautioned that adjuvant therapy does not completely eliminate the risk of recurrence.
B Physicians caution that targeted therapy is not recommended if the LVEF is less than 50% or if concurrent anthracycline therapy is being administered. Before adjuvant targeted therapy was started, the physician rechecked HER-2 status and checked cardiac function.
The physician recommended that adjuvant therapy be continued with trastuzumab, either once every 3 weeks or once a week, for a full 1 year, and advised that the benefit would be greater if started early. Targeted therapy can be used concurrently with chemotherapy or in sequence, with anthracyclines in pre- and post-sequence. If there is concern about cardiotoxicity of trastuzumab, a non-anthracycline agent may be chosen for combination chemotherapy.
During treatment with trastuzumab, physicians recommend periodic ultrasound examinations.
Can advanced breast cancer receive targeted therapy?
Ms. A successfully completed neoadjuvant and adjuvant targeted therapy, but metastases were found on review several years later, and Dr. B advised that both recurrent and metastatic breast cancer are considered advanced breast cancer and that the goal of treatment is to control the disease, improve quality of life, and extend survival as appropriate.
Dr. B still reviewed cardiac function and fully evaluated Ms. A’s overall condition, including blood work, ECG, etc.
Dr. B noted that a combination regimen centered on anti-HER-2 is still available for advanced breast cancer, including trastuzumab in combination with chemotherapeutic agents, with a choice of paclitaxel (with or without carboplatin), docetaxel, vincristine, capecitabine, etc., but try not to use anthracyclines concurrently, or sequentially if anthracyclines are necessary. For those who develop disease after treatment with trastuzumab, like Ms. A, trastuzumab can be kept but replaced with other chemotherapy drugs, or switched to lapatinib plus other chemotherapy drugs, or choose dual-targeted therapy, or use T-DM1. targeted therapy can be carried out until it is not tolerated or the disease progresses.
After fully understanding the characteristics, uses, and adverse effects of targeted therapy, Ms. A received targeted therapy again, and her disease was effectively controlled with no significant decrease in quality of life, and she continues to cooperate with her physician on targeted drug maintenance therapy.