HER2-Positive Breast Cancer

The subtype of breast cancer that is HER2-positive breast cancer (or simply HER2+ breast cancer) marks a more advanced and aggressive type of breast cancer owing to the human epidermal growth factor receptor 2 (HER2) gene overexpression or amplification. At Protheragen, we offer comprehensive preclinical development services for HER2-positive breast cancer diagnostics and therapeutics.

Overview of HER2-Positive Breast Cancer

HER2-positive breast cancer is a form of breast cancer induced by the overexpression of the human epidermal growth factor receptor 2 (HER2) gene. Overexpression of the gene results in uncontrolled cell division, movement, and survival, which worsens the prognosis of the patients. HER2-positive breast cancer patients represent nearly 20% of the total breast cancer patients, as well they carry a greater risk of having recurrences and poor prognosis than the other subtypes of breast cancer. The diagnosis of HER2 as a target vulnerable to therapeutic intervention has made it possible to utilize targeted therapies for this subtype with the use of monoclonal antibodies, antibody-drug conjugates, which have largely benefited these patients.

Fig.1 Mechanism of action of HER2 tyrosine kinase inhibitors. (Schlam I., et al., 2021)

Pathogenesis of HER2-Positive Breast Cancer

Amplification of the HER2 gene, leading to increased expression of the receptor on the cell surface, is the most important reason for the development of breast cancer with HER2 positivity. Such overexpression results in the tumor growth, movement, and survival by activating peripheral signaling pathways like PI3K/Akt, ERK (p42/p44 MAPK), and NF-κB, which are dominantly activated. Dimerization of HER2 receptors with other members of the HER family (HER1/EGFR, HER3, HER4) also contributes more to signaling activity. The absence of a known HER2 ligand means that its activity is mostly controlled through dimerization, which makes dimerization a highly prospective target for therapy.

Diagnostics Development for HER2-Positive Breast Cancer

Fluorescence In Situ Hybridization (FISH)

Fluorescence in situ hybridization is regarded as the most definitive method for determining a patient's HER2 status. In FISH, probes that emit light are utilized to identify the increased copies of the HER2 gene within the cell nuclei. If the number of signals for HER2 relative to the centromeres of chromosome 17 is greater than 2, the test result for HER2 amplification is considered positive. FISH has greater sensitivity and specificity than IHC.

Immunohistochemistry (IHC)

Immunohistochemistry is one of the most common diagnostic methods used to assess HER2 status in breast cancer. This method utilizes antibodies to ascertain whether there is an overexpression of the HER2 protein in the tissue. The output is scored from zero to three, with three indicating overexpression or, rather, overexpression in the tissue examined. IHC is not very complicated and is possible in most surgical pathology laboratories.

Therapeutics Development for HER2-Positive Breast Cancer

Monoclonal antibodies, such as trastuzumab (Herceptin) and pertuzumab (Perjeta), are fundamental to HER2-targeted therapy, inhibiting HER2 activity and preventing receptor dimerization, often used in combination with chemotherapy. Antibody-drug conjugates (ADCs) like T-DM1 (Kadcyla) and T-DXd (Enhertu) deliver cytotoxic drugs specifically to cancer cells, showing significant efficacy, especially in patients resistant to other HER2-targeted therapies. Tyrosine kinase inhibitors (TKIs), including lapatinib (Tykerb) and tucatinib (Tukysa), block HER2 kinase activity and downstream signaling, with tucatinib demonstrating efficacy in brain metastases. Bispecific antibodies, such as zanidatamab (ZW25), target multiple epitopes on HER2, enhancing therapeutic efficacy. CAR-T cell therapy, which engineers T cells to target HER2-positive cancer cells, has shown promise in preclinical and early-phase clinical trials, offering a potent immune response and potential to overcome resistance.

Table 1. Bispecific antibodies for HER2+ breast cancer in clinical trials. (Mercogliano M. F., et al., 2023)

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

Protheragen offers comprehensive diagnostics and therapeutics development services for HER2-positive breast cancer. Our services include the development and validation of diagnostic assays, preclinical research, and customized solutions tailored to meet the specific needs of our clients. We leverage cutting-edge technologies and scientific expertise to accelerate the development of innovative therapeutics and diagnostics for this aggressive subtype of breast cancer.

Diagnostics Development

• Karyotype Analysis Service
• Omics Analysis Service
• Biomarker Development Service
• Artificial Intelligence Service
• Customized Diagnostics Development

Therapeutic Development

• Anticancer Peptide
• Gene Therapy
• Immunotherapy
• Monoclonal Antibody
• Phytotherapy
• Small Molecule Drug
• Therapeutic Cancer Vaccine

Disease Models

• SK-BR-3 Cell-Derived Xenografts (CDX) Models
• MDA-MB-453 Cell-Derived Xenografts (CDX) Models
• MMTV-Neu Transgenic Mouse Models
• MMTV-PyMT Transgenic Mouse Models

Protheragen offers customized services to meet the unique requirements of our clients. Our team works closely with clients to develop tailored solutions, from designing specific diagnostic assays to conducting bespoke preclinical studies. If you are interested in our services, please feel free to contact us.

References

• Schlam, Ilana, and Sandra M. Swain. "HER2-positive breast cancer and tyrosine kinase inhibitors: the time is now." NPJ breast cancer 7.1 (2021): 56.
• Mercogliano, María Florencia, et al. "Emerging targeted therapies for HER2-positive breast cancer." Cancers 15.7 (2023): 1987.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.