What Is HER-2 Positive Breast Cancer?
HER2-positive breast cancer is a type of breast cancer where the cells have higher levels of a protein called HER2. This protein normally helps regulate cell growth, but when there are too many HER2 proteins, it can cause the cancer cells to grow and divide more quickly. This type of breast cancer tends to be more aggressive and faster-growing compared to other types. HER2-positive breast cancer can also occur in other types of cancers, such as bladder, gastrointestinal, ovarian, and stomach cancers. About 20 % of all breast cancer cases fall under this subtype, which has a worse prognosis and a higher chance of recurrence.
What Is the Pathogenesis of HERS-2 Positive Breast Cancer?
The pathogenesis of HER2-positive breast cancer involves the overexpression or amplification of the human epidermal growth factor receptor 2 (HER2) gene, which leads to the production of excessive HER2 protein on the surface of cancer cells. This abnormality in the HER2 gene is usually acquired during the development of breast cancer cells.
The HER2 protein is essential for cell survival, division, and growth. The amount of HER2 protein is strictly controlled in healthy cells. The HER2 gene is amplified or overexpressed in HER2-positive breast cancer, which results in an excess of HER2 protein. As a result, the HER2 pathway receives more signals, which encourages the unregulated growth and division of cancer cells.
How Is HERS-2 Positive Breast Cancer Diagnosed?
The most commonly used diagnostic test is immunohistochemistry (IHC), which assesses the protein expression of HER2 on tumor cells. Another test is fluorescent in situ hybridization (FISH), which detects HER2 gene amplification. Both tests provide essential information to classify breast cancer as HER2-positive or HER2-negative. Early diagnosis and appropriate treatment interventions contribute to better prognosis and quality of life for patients with HER2-positive breast cancer.
1. Immunohistochemistry (IHC):
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Procedure: Immunohistochemistry is a technique that utilizes specific antibodies to detect and visualize proteins within tissue samples. For the diagnosis of HER2-positive breast cancer diagnosis, IHC involves staining breast cancer tissue sections with an antibody against HER2. The intensity of staining and distribution of HER2 protein is assessed microscopically, providing information on HER2 status.
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Result: A standardized scoring system, often based on the HercepTest or the Dako scoring criteria, is used to interpret IHC data for HER2 testing. The scoring system divides Results into four groups: 0, 1+, 2+, and 3+. A score of 3+ denotes the presence of the HER2 protein, which is strongly and consistently expressed. Scores of 0 and 1+ indicate a negative HER2 status, whereas 2+ suggests an equivocal or borderline status that needs further investigation.
2. Fluorescent in Situ Hybridization (FISH):
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Procedure: Fluorescent in Situ Hybridization is a molecular cytogenetic technique that uses fluorescently labeled DNA probes to detect and visualize specific DNA sequences within individual cells. FISH uses DNA probes that target the HER2 gene area in the context of HER2 testing, enabling the evaluation of HER2 gene amplification in breast cancer cells.
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Result: FISH results are interpreted by examining the ratio of HER2 gene copies to a reference gene (usually chromosome 17 centromere) within tumor cells. The HER2 gene-to-reference gene ratio determines the HER2 status. Ratios greater than a predefined threshold indicate HER2 gene amplification, indicative of HER2-positive status.
How Is HERS-2 Positive Breast Cancer Treated?
The precise course of treatment for HER2-positive breast cancer will depend on a number of variables, including the disease's stage, the patient's general health, and other particular considerations. Finding the best course of therapy for a person's unique circumstances necessitates consultation with a medical staff with breast cancer expertise. Combinations of medicines are frequently used to treat HER2-positive breast cancer in order to target the cancer cells efficiently. The therapy strategy could consist of the following:
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Targeted Therapy: Trastuzumab, Pertuzumab, and Ado-trastuzumab emtansine are commonly used drugs that target the HER2 protein. These drugs work to stop the development and spread of cancer cells by blocking the HER2 protein or interfering with its signaling pathways. They have significantly improved outcomes for individuals with HER2-positive breast cancer by specifically targeting and blocking the effects of HER2 overexpression.
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Chemotherapy: To eliminate cancer cells throughout the body, chemotherapy medications may be used with targeted therapy. Commonly given chemotherapy medications include Docetaxel, Doxorubicin, and Cyclophosphamide.
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Hormone Therapy: When a malignancy has a positive hormone receptor (either an estrogen or progesterone receptor), hormone therapy may be suggested. Drugs like Tamoxifen and aromatase inhibitors can aid in preventing the impact of hormones on the development of cancer cells.
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Surgery: Surgical options include mastectomy (removal of the entire breast) and lumpectomy (removal of the tumor plus a small quantity of surrounding tissue). In order to determine whether the cancer has progressed to neighboring lymph nodes, lymph node excision may also be necessary.
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Radiation Therapy: Following surgery, radiation therapy is often carried out to target any cancer cells that are still present in order to lower the likelihood of a recurrence. It includes employing high-energy lasers to either kill or stop the development of cancer cells.
Our comprehension of HER2-positive breast cancer is being improved, and clinical studies are being conducted to create more efficient therapies. To possibly lessen the need for chemotherapy and its attendant adverse effects, one emphasis is investigating the use of newer antibodies as a stand-alone therapy. In addition, measures are being taken to deal with potential treatment resistance.
Future Directions:
Combination HER2-Directed Therapy:
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The combination of Lapatinib and Trastuzumab has shown synergistic effects and improved progression-free survival in HERS-2-positive breast cancer.
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Combination therapies targeting different pathways are also being investigated.
mTOR Inhibition:
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mTOR inhibitors, such as Rapamycin in combination with Trastuzumab, have clinical activity in combination with anti-HER2 agents. Agents like PI3K inhibitors and Metformin are also being evaluated for mTOR inhibition.
Conclusion:
Advancements in research and personalized medicine continue to expand treatment options and improve the prognosis for patients with HER2-positive breast cancer. By tailoring treatment strategies to individual patients and ensuring ongoing monitoring and follow-up, we can enhance the management and overall outcomes of this challenging disease. Additionally, advancements in precision medicine and personalized treatment approaches hold great promise for further improving outcomes for patients with HER2-positive breast cancer.
