In the year 2020, 2.3 million women were diagnosed with breast cancers around the world with over 685,000 fatalities reported worldwide. (WHO report). The incidence of breast cancer has increased almost by 50% between 1965 and 1985.
Being the most widely prevalent malignancy among women in India, the surge of breast cancer cases in India make it one of the leading causes of premature death in the country. Chemotherapy, radiation therapy and surgery are the three cancer modalities that have formed the cornerstone for breast cancer treatment across the world and are deemed to be the standard lines of treatment for this cancer type.
Over the past decade, a new group of treatments have come to the forefront of treating cancer and they are targeted therapy drugs. Targeted therapy drugs employ pharmacologically induced substances that result in cell death and inhibit cancer cell growth. Targeted therapy for breast cancer employs substances or drugs which block the growth of cancer by interfering with operations of specific molecules and receptors which are responsible for cell proliferation and survival.
Patients whose breast cancer cells overexpress certain characteristic proteins on their surface, allowing an abnormal growth pattern may benefit from targeted therapy drugs. The most commonly employed and deemed to be the most efficient targeted therapy is the one targeting the HER2 protein on the surface of breast cancer cells.
In HER2 positive breast cancers, the HER2 (human epidermal growth factor receptor 2) gene doesn’t work correctly and ends up making too many copies of itself. These extra HER2 genes make too many proteins known as HER2 receptors. These HER2 receptors receive signals that stimulate a cell to proliferate and grow.
However, breast cancer cells with too many HER2 receptors can pick up excessive growth signals thereby resulting in breast cells to grow and divide in an uncontrolled manner.
Anti HER2 drugs or HER2 targeted therapies, attach themselves to the HER2 receptor proteins on the surface of breast cancer cells. These drugs then block the HER2 receptors from receiving the growth signals in HER2 positive breast cancer. By putting a halt on these growth signals HER2 targeted therapies slow down or stop the growth of HER2-positive and HER2- low breast cancer.
Factors To Consider For Anti HER2- Therapy
Many HER2 targeted therapy drugs are administered in combination with other lines of treatment such as chemotherapy. Some of these HER2 drugs carry chemotherapeutic agents directly to the HER2 positive cancer cells, which can help to protect the healthy cells from the toxic effects of chemotherapy drugs.
There are various factors that oncologists consider before deciding whether a patient will truly benefit from this targeted therapy. Some of these factors include –
- The stage and size of the cancer.
- Whether the cancer is HER2- positive or HER2- low.
- Any previous treatments availed.
- The status of the cancer after previous treatment availed.
- The side effects associated with HER2 targeted therapy drugs.
Along with this it is recommended that women who are pregnant or have future plans regarding pregnancy should not consider targeted therapies as a line of treatment for their cancer.
Drugs That Target The HER2 Receptor
Monoclonal Antibodies
Developed in the lab, monoclonal antibodies work like the antibodies made naturally by the immune system in our body. Along with targeting the HER2 receptor, these medications combat the malignant breast cancer cells by alerting the immune system and its responses to get rid of the cancer in the body.
Due to this function, they are also referred to as immune targeted therapies. These drugs are administered through intravenous infusion and allow them to directly enter the bloodstream. Trastuzumab is a monoclonal antibody that is commonly used to treat early stage and advanced HER2 positive breast cancer and can be administered in combination with chemotherapy and another targeted therapy drug known as Pembrolizumab.
Margetuximab is used in combination with chemotherapy to treat people diagnosed with metastatic HER2-positive breast cancer who have been treated previously with 2 or more anti-HER2 regimens. Pertuzumab is used in combination with Trastuzumab and other chemotherapy drugs to treat HER2- positive metastatic breast cancer that has not been treated with Trastuzumab or chemotherapy yet.
Antibody Drug Conjugates
Antibody-drug conjugates (ADCs) is a pharmaceutical product in which a monoclonal antibody is engineered to utilize the capability of monoclonal antibodies by combining them to cytotoxic agents. Chemotherapy with its poor specificity towards tumor tissues is often associated with a poor therapeutic response and can cause substantial damage to the healthy tissues of the body.
However, unlike chemotherapy, ADCs specifically target and attack the cancer cells without harming the healthy cells of the body by integrating the antigen specificity of the monoclonal antibodies with antibody fragments. There are 3 ADCs that include trastuzumab that can be employed for the treatment of breast cancer.
Enhertu (chemical name: am-trastuzumab-derux tecan-ki), can be employed for the treatment unresectable or metastatic HER2-positive breast cancer in patients who have previously received an anti-HER2 medication for metastatic disease or before or early stage disease that has recurred within 6 months of completing treatment.
Summary
Targeted therapy for cancer treatment is a rapidly growing field of research and has shown great promise over the last 20 years. By targeting proteins that control how cancer cells grow, divide and spread, targeted therapy specifically attacks cancer cells as opposed to the one-size-fits-all approach seen in conventional lines of treatment for cancer.
