American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer

Abstract

The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly available types of brightfield ISH, is proposed. Elements to reliably reduce assay variation (for example, specimen handling, assay exclusion, and reporting criteria) are specified. An algorithm defining positive, equivocal, and negative values for both HER2 protein expression and gene amplification is recommended: a positive HER2 result is IHC staining of 3+ (uniform, intense membrane staining of > 30% of invasive tumor cells), a fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or a FISH ratio (HER2 gene signals to chromosome 17 signals) of more than 2.2; a negative result is an IHC staining of 0 or 1+, a FISH result of less than 4.0 HER2 gene copies per nucleus, or FISH ratio of less than 1.8. Equivocal results require additional action for final determination. It is recommended that to perform HER2 testing, laboratories show 95% concordance with another validated test for positive and negative assay values. The panel strongly recommends validation of laboratory assay or modifications, use of standardized operating procedures, and compliance with new testing criteria to be monitored with the use of stringent laboratory accreditation standards, proficiency testing, and competency assessment. The panel recommends that HER2 testing be done in a CAP-accredited laboratory or in a laboratory that meets the accreditation and proficiency testing requirements set out by this document.

Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma

“…Positive hormonereceptor (HR) status was defined as C10 % of cells stained positive for oestrogen (ER) and/or progesterone receptor (PgR), HER2-receptor was positive if either local or central immunohistochemical staining was 3? or fluorescent in situ hybridization was amplified (ratio of HER2/CEP17 [ 2.2) [13]. Central assessment was used whenever available.…”

Long non‐coding RNA SNHG14 induces trastuzumab resistance of breast cancer via regulating PABPC1 expression through H3K27 acetylation

“…About 15%‐20% of breast cancer patients are accompanied with overexpression of human epidermal growth factor receptor 2 (HER2), ended up with poorer prognosis and survival 3, 4. Currently, therapy with anti‐HER2 mono‐antibody such as trastuzumab is applied to treat HER2‐positive breast cancer patients 5, 6. Trastuzumab is designed to target HER2 and silence its function, and is mostly used for early stage or metastatic gastric and breast cancer patients with positive HER2 mutations.…”

Genomic profiling identifies GPC5 amplification in association with sarcomatous transformation in a subset of uterine carcinosarcomas

“…Adapting the conservative cut‐off values established for scoring HER2 FISH in breast carcinoma, as per the 2007 ASCO/CAP Guidelines 7 ( GPC5/CEP13 ratio ≥ 2.2 for high‐copy gain, and ≥ 1.5 but < 2.2 for low‐copy gain), amplification of GPC5 was detected exclusively in the sarcoma component in five cases (Cases #1,2, 3, 6, and 9; Table 2 and Figure 3D,F). In addition, one case harboured high‐copy amplification throughout the tumour (Case #5).…”