Human epidermal growth factor receptor 2 (HER2)

Human epidermal growth factor receptor 2 (HER2)

The history behind the antibody

The concept behind the use of HER2 was first developed at the start of 1982, and it became confirmed in 1984. The initial discovery was a result of the effort of American-based scientists who work tirelessly at the Robert Weinberg Group. The group was divided into three based on the geographical location. One group was based in the Massachusetts university, another group was based in the University of, and the last group of the Robert Weinberg was situated at the Harvard University.  The Robert Weinberg group performed lab works and categorized all breast cancers as either HER2 positive or negative. The categories that were known to be HER2 positive tested positive in the presence of protein HER2 while the HER2 negatives tested negative in the presence of protein HER2. The protein HER2 is responsible for promoting growth in tumor cells. The focus of the lab works performed by the group was to interlink four vital disciplines that contributed greatly to the field of oncology. Among the four disciplines that were united by the group included immunology, genetics, pathology as well as the pharmacological aspect. This explains the success route taken by the integration of the interrelated disciplines, which has been termed as the interdisciplinary integration. Through their works, the field of oncology has improved both pathologically and pharmacologically (Jordan et al., 102-106).

An isolated monoclonal antibody form the HER2 protein was identified as viable after several kinds of research peaked in 1998. The studies conducted in 1998 identified the need for targeted therapy for cancer patients. As a result, a counter HER2 was developed and named trastuzumab, which was an anti-HER2. The later was developed by scientists from Genentech Inc. based in California. The discovery paved the way for numerous approaches to tumor management, including a deeper analysis of tumor biology.

A protocol on using the antibody

Guidelines on the clinical use of HER2 had been developed by pathology and oncology experts to promote clarity in the test results. The following protocols apply when it comes to the use of HER in cancer therapy.

1. Initially, a repeat of the HER2 test for all biopsies that tested negative was mandatory. However, the new guideline states that a HER2 test may or may not be ordered for specimens that tested negative except for advanced tumors such as grade 3.
2. There should be an in-depth, rigorous interpretation of the less common patterns that tend to emerge with HER2 tests. About five percent of all HER2 test cases exhibit less common scenarios and patterns that need rigorous analysis and interpretation. The unique patterns are evident when then HER2 status performed in breast tumors are evaluated through the use of the common ISH tests. The emerging groups have been categorized into groups 2,3, and 4. A proposed assessment criterion for the emerging patterns is through the use of reviewed IHC tests. Such an approach will be vital in assisting the pathologist in determining whether an excised tumor biopsy is either HER2-positive or negative.
3. The oncology and pathology experts proposed the use of a dual probe at the expense of single-probe ISH tests. The experts further made it known that the single-probe ISH has regulatory principles regarding its use in most countries across the world. Therefore, pathologists and oncologists should not rely too much on it, but rather on the dual-probe.

Use in current day pathology

Knowledge of HER2 contributed to the development of drugs that targets the receptor. Hence stopping the aggressive multiplication of HER2 positive tumors. One of the drugs that target the HER2 is the trastuzumab commonly widely known as the Herceptin. The drug is active against all the HER2-positive tumors, and it works by blocking the breast cancer cells from receiving growth signals. As a result, the cells are unable to multiply rapidly, as in the case with HER2 positive cancers. Oncologists have demonstrated that drugs that target the HER2 are effective in managing HER2 positive tumors and has proved effective for breast cancer patients all over the world (Loibl and Luca, 2415-2429).

Due to the decreased effectiveness of the trastuzumab, another drug known as pertuzumab was developed. Just like the trastuzumab, pertuzumab is less effective on its own. As a result, the oncologist suggested a combination of the two drugs in the management of HER2 positive cancers, which they identified to be more effective as compared to individual therapy.  A further report indicated that a combination of trastuzumab, pertuzumab, and chemotherapy yielded a profound effect on cancer management. However, pertuzumab has a slightly distinct domain compared to the trastuzumab. What is common between the two antibodies is that they both target the HER2, which is the core determinant of cancer growths. Oncologists determine cancer subtypes by measuring the amount of estrogen content that is present in the HER2 so that to develop an appropriate therapy. Both hybridization and immunohistochemistry have been identified as an effective method for measuring HER2 in cancerous cells (Von Minckwitz, Gunter, et al., 122-131).

Pictures of antibody histology

Works cited

Von Minckwitz, Gunter, et al. “Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer.” New England Journal of Medicine 377.2 (2017): 122-131.

Loibl, Sibylle, and Luca Gianni. “HER2-positive breast cancer.” The Lancet 389.10087 (2017): 2415-2429.

Jordan, Nicole Vincent, et al. “HER2 expression identifies dynamic functional states within circulating breast cancer cells.” Nature 537.7618 (2016): 102-106.