Pertuzumab Therapy and ERBB2 Genotype

Review
In: Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012.
[updated ].

Excerpt

Pertuzumab (brand name, Perjeta) is a monoclonal antibody used in the treatment of breast cancer. Pertuzumab was designed to target an epidermal growth factor receptor encoded by the ERBB2 gene, commonly referred to as the HER2 gene.

The ERBB2 gene is overexpressed in 15–20% of breast cancers and is also overexpressed in some cases of other cancer types (gastric, colon, head, and neck). Historically, “HER2-positive” tumors are associated with a faster rate of growth and a poorer prognosis than other breast cancer subtypes. The use of pertuzumab in treatment regimens improves outcomes, with limited adverse effects that include cardiac toxicity.

Pertuzumab is used with other drugs as an advanced breast cancer treatment, a neoadjuvant treatment, and an adjuvant treatment for HER2-positive breast cancer. In the advanced/metastatic setting, pertuzumab added to trastuzumab and a taxane is used to increase long-term progression-free and overall survival when administered in the first line setting. As neoadjuvant treatment, pertuzumab is given with trastuzumab and chemotherapy before surgery in individuals with early breast cancer to increase pathologic complete response rates. And as an adjuvant treatment, pertuzumab is given with trastuzumab and chemotherapy to reduce the risk of cancer reoccurrence in individuals with early breast cancer (Table 1).

The 2020 FDA-approved drug label states that pertuzumab should only be used to treat individuals with tumors that have either HER2 protein overexpression or ERBB2 gene amplification, as determined by an accurate and validated FDA-approved assay. This is because these are the only individuals studied for whom benefit has been shown (1).

The most recent update (2018) American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) guidelines continue to state that all newly diagnosed individuals with breast cancer must have an HER2 test performed. Individuals who then develop metastatic disease must have an HER2 test performed in a metastatic site, if a tissue sample is available (2).

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