HER2 Positive Breast Cancer is a form of breast cancer that is caused by a mutation of a gene called the HER2. The mutation causes the cancer cells to become a particular type of cancer called HER2 Positive Breast Cancer. There are several different treatments for this cancer, such as chemotherapy and radiation therapy. However, there are some things that you need to know about this type of cancer before you decide to get treated for it.
Radiation therapy
HER2-positive breast cancer is one of the most common forms of breast cancer. It accounts for 20-25% of newly diagnosed breast cancer cases. This form of breast cancer is usually treated with chemotherapy, surgery, or a combination of both. Some women will also receive a targeted drug like Herceptin, T-DM1, or Perjeta.
One of the most common types of radiation therapy used to treat breast cancer is called external beam radiation. It uses protons, X-rays, or other particles to kill cancer cells. It can be given as a treatment for several weeks or as an outpatient procedure.
Other types of radiation therapy include brachytherapy, which involves placing a device with radioactive seeds in breast tissue. This type of treatment has fewer side effects than external beam radiation.
One of the best things about radiation therapy is that it’s painless. In fact, it can reduce the risk of cancer returning by a considerable amount. It also can help relieve symptoms of an advanced form of the disease.
Some women also receive chemotherapy in conjunction with radiation therapy. This can help kill cancer cells that remain after surgery or after a mastectomy. The combination can reduce the risk of cancer recurrence by up to 67%.
One study found that patients who received radiation therapy followed by chemotherapy had a better chance of survival five years after treatment. This study was based on data from 103 patients.
The best abscopal effect was achieved with a 24-Gy dose administered in three fractions of eight Gy. This was the largest dose delivered in a study.
HER2-positive breast cancer patients may also receive brachytherapy, which uses radioactive pellets to kill cancer cells. Brachytherapy is usually given through small tubes in the breast.
Chemotherapy
HER2-positive breast cancer is a subtype of breast cancer that is more aggressive than other types. While some people with HER2-positive breast cancer may receive HER2-directed therapy along with chemotherapy, most people will receive chemotherapy alone.
HER2-positive breast cancer is diagnosed when a patient’s breast cancer cells produce too much of the growth-promoting protein HER2 or human epidermal growth factor receptor 2. These cancer cells grow faster than other cancer cells and have a higher risk of recurrence and death. This protein controls the growth of cancer cells, so blocking it can help treat cancer.
The most common chemotherapy treatment for HER2 positive breast cancer is neoadjuvant chemotherapy. This treatment reduces the size of the tumor before surgery. It can be given as early as four to six weeks after surgery.
Another treatment for HER2 positive breast cancer is targeted treatment, which uses monoclonal antibodies to attach to HER2 proteins on cancer cells. These antibodies can help prevent cancer from growing. These monoclonal antibodies work by blocking the HER2 protein from doing its job, causing cancer cells to die.
Other treatments include immunotherapy, which works by activating the immune system to fight cancer. Some breast cancer patients may also receive hormone therapy, which lowers estrogen levels. Other forms of treatment include surgery, which is less common than chemotherapy, and HER2-directed therapy. Depending on the stage of cancer, a patient’s health and desire to continue treatment may also factor into their treatment options.
If cancer has spread beyond the breast, some patients may have to undergo chemotherapy. This treatment may help slow the growth of cancer, but it can also have some nasty side effects. These side effects may increase as the treatment progresses. Typically, chemotherapy is given in cycles, so that the body can get rid of the harmful effects of the chemotherapy.
Trastuzumab
HER2-positive breast cancer is an aggressive form of cancer with a high rate of recurrence. There are two main types of treatment for HER2-positive breast cancer: neoadjuvant chemotherapy and HER2-targeted therapy. Both of these treatments can be very effective. But the decision to use these treatments is based on the individual patient’s medical history, the stage of cancer, and personal preferences.
Most people with HER2-positive breast cancer receive neoadjuvant chemotherapy. This is a treatment where the cancer is treated with chemo that kills cancer cells and then the body can recover from side effects. After chemo, some patients may take a daily pill called hormone-driven therapy. Another treatment for HER2-positive breast cancer is the use of a monoclonal antibody, called trastuzumab, which is given after chemo.
Trastuzumab is an antibody that blocks the action of HER2, one of four tyrosine kinases that play a role in the growth of cancer cells. It is used to treat early-stage breast cancer and advanced HER2-positive cancers.
In the HERA trial, patients who had been treated with trastuzumab had a 46% reduction in recurrences after two years. The study used the IQVIA Oncology Electronic Medical Records database, which included patients with at least 60 days of follow-up. The data included information on age, gender, disease stage, and nodal status.
The HERA trial was not the only study to evaluate HER2-targeted therapy. Two other studies have shown similar results but with significantly higher ER-positive rates. Regardless of the results, the study highlights the need for more effective treatments for HER2-positive metastatic breast cancer.
The study found that trastuzumab is associated with a lower rate of recurrences, as well as a lower cost. However, there were no significant differences between the groups in tpCR, distant recurrence, or local recurrence.
BiTE approach
HER2+ breast cancer has historically been an aggressive subtype of the disease. However, in recent years, the landscape of HER2+ early-stage breast cancer has changed dramatically. The use of novel anti-HER2 therapies has greatly improved the survival of patients with HER2+ breast cancer.
The current standard of care is to tailor the intensity of adjuvant treatment to the individual patient’s risk. The decision to escalate or de-escalate treatment depends on the tumor stage, the presence of a pCR, and the patient’s medical history.
In the early stages of breast cancer, neoadjuvant therapy is often given to reduce the size of the tumor before surgery. HER2-targeted therapy is frequently used in conjunction with chemotherapy. Currently, the most common drugs used in the treatment of HER2+ breast cancer are pertuzumab (Perjeta) and trastuzumab (Herceptin).
The most important clinical question is whether to de-escalate therapy. In low-risk patients, de-escalation strategies can produce excellent long-term outcomes. Despite these benefits, the risk of overtreatment is still significant. This may be because of the heterogeneity of tumors. Fortunately, there are several strategies for de-escalation, including ctDNA testing, which may be less invasive and less expensive.
De-escalation strategies for HER2+ breast cancer have been studied in several clinical trials. These studies have shown that the de-escalation of adjuvant therapy can lead to a decrease in toxicity. Moreover, a reduction in tumor burden has been shown to reduce the risk of recurrence.
De-escalation strategies for T1b HER2+ breast cancer have been studied through the use of taxane emtansine (T-DM1). The use of T-DM1 has led to a strong rationale for neoadjuvant therapy, though it must be balanced against the risk of overtreatment.
Downstream signaling pathways
HER2 activates several downstream signaling pathways to initiate cellular processes such as cell proliferation, migration, and apoptosis. However, the exact role of HER2 in oncogenesis is unclear. In breast cancer, HER2 is overexpressed in 25-30% of tumors. Amplification of the HER2 gene has been shown to be associated with poor prognosis in BC patients.
HER2 plays a key role in activating MAPK pathways. Its protein kinase activity is similar to that of EGFR. It contains a Src homology 2 (SH2) domain that recognizes tyrosine-phosphorylated sites on receptors. When phosphorylated, HER2 provides docking sites for downstream effectors such as phosphoinositide 3-kinase/AKT (PI3K/AKT) and mitogen-activated protein kinase (MAPK). In HER2-positive breast cancer, overexpression of HER2 leads to ligand-independent dimerization and constitutive activation of several downstream signaling pathways.
In addition, HER2 has been reported to enhance EGFR activity. However, the mechanism of HER2-induced EGFR activation is unclear. In vivo studies have shown that inhibition of HER2 dimerization reduces the activity of PI3K/AKT. HER2 is naturally prepared for dimerization. The phosphorylation of HER2 results in the activation of downstream signaling pathways and increases cell survival. It also enhances drug delivery to tumors.
In addition to regulating HER2, TRAF4 also plays a critical role in regulating the stability of HER2. TRAF4 binds to the intracellular domain of the HER2 receptor. The binding of TRAF4 to HER2 inhibits the binding of SMURF2 to HER2. TRAF4 and SMURF2 also possess E3 ligase activities, which stabilize the target molecule. When SMURF2 ubiquitinates HER2, the receptor becomes dephosphorylated and degraded. This may also play a role in regulating the HER family.
Inhibition of HER2 dimerization has also been shown to suppress HER2-mediated cell signaling. Inhibition of HER2 signaling also contributes to the development of drug resistance.
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