Assessment of HER2 testing patterns, HER2+ disease, and the utilization of HER2-directed therapy in early breast cancer

Abstract

ContextDetermining human epidermal growth factor receptor 2 (HER2) status is critical for the management of early-stage breast cancer (ESBC). An understanding of HER2 testing practices can provide insight into how test results influence the use of HER2-directed therapy.ObjectiveTo assess HER2 testing, HER2+ disease, and HER2-directed therapy in ESBC at the Huntsman Cancer Institute before and after the 2007 American Society of Clinical Oncology and College of American Pathologist (ASCO/CAP) guidelines on HER2 testing were published.MethodsPatients were identified from an institutional tumor registry. HER2 testing patterns and results were examined using a chart review of pathology and clinical notes. Patient characteristics, HER2+ rate, and trastuzumab use were evaluated descriptively. Discordance rate with reflex testing (immunohistochemistry [IHC]2+ retested by fluorescence in situ hybridization [FISH]) was also evaluated.ResultsA total of 1,459 women were included (mean age: 57 years). The rate of HER2+ disease was 17% (number [N] =245). The discordance rate between IHC2+ and FISH was 10%. After the 2007 ASCO/CAP guidelines, fewer tumors were classified as IHC3+ (16% post- versus 21.9% pre-2007), more tumors were characterized as IHC2+ (26.4% post- versus 20.7% pre-2007), and the overall HER2+ rate was decreased (18.7% versus 21.9%), but this was not statistically significant (P=0.519). Most patients with HER2+ ESBC received HER2-targeted therapy (N=185).ConclusionThe HER2+ rate was 17% and within the range of the reported rates in the literature. Reflex testing identified additional HER2+ tumors by approximately 10%, and should be considered a potential quality indicator. ASCO/CAP HER2 testing guidelines in 2007 appeared to impact the interpretation and classification of HER2+ tumors.

The Global Need for a Trastuzumab Biosimilar for Patients With HER2-Positive Breast Cancer

“…19 Observational studies on real-world treatment patterns in patients diagnosed with and/or treated for HER2 þ EBC between 2005 and 2015 suggest that 19.1% to 59.5% in the United States, Canada, Australia, New Zealand, United Kingdom, The Netherlands, Germany, and China did not receive neoadjuvant or adjuvant trastuzumab (Table 1). [23][24][25][30][31][32][34][35][36][37][39][40][41]44,45 Use of trastuzumab was somewhat less in patients with small ( 1 cm) and/or node-negative HER2 þ tumors, 28,30,40,41,44 in whom the benefits of adjuvant trastuzumab therapy are somewhat controversial. 7,9,10 Several studies conducted between 2006 and 2013 also suggest that older patients with HER2 þ EBC and patients with HER2 þ /hormone receptor (HR)-positive disease were less likely to receive trastuzumabbased therapy (Table 1).…”

“…Few studies in patients with EBC, and none in patients with MBC, reported reasons for patients not receiving anti-HER2 therapy. 23,25,30,32,36,37,40,44 Furthermore, it is not clear how often HER2 blockade is continued in multiple lines of systemic therapy for metastatic disease. In the adjuvant setting (Table 1), trastuzumab was withheld from patients because of advanced age (11%-23%), increased risk of cardiac toxicity (15%-46.4%), or other comorbidities (approximately 12%).…”

Evaluation of Lapatinib and Trastuzumab for Ototoxic Effects

“…Because these two chemotherapy drugs are used sequentially or combined with other chemotherapy drugs, clinical studies have not been planned. In the literature, erlotinib and imatinib dependent ototoxicity have been reported, as they are tyrosine kinase inhibitors that effect ototoxicity along a different pathway [1,6,9] . When we examine the studies relating tyrosine kinase inhibitors to hearing loss, many of them displayed mechanisms related to EGFR and HER [10,11] .…”

“…Trastuzumab is a humanized recombinant monoclonal antibody that acts on the extracellular portion of the HER2 protein [1] . Lapatinib (Tykerb®; Glaxo-Smith Kline) is a tyrosine kinase inhibitor that suppresses epidermal growth factor 1 (EGF-1) and intracellular phosphorylation of the HER-2/neu receptor.…”

Tumor markers currently utilized in cancer care

“…HER2 HER2 is also known as HER2/neu, erbB-2, or EGFR2 [67]. This cellular receptor may contribute to the growth and/or dissemination of certain types of tumors [14,67,68]. HER2 overexpression is found in 20% of patients with breast cancer [13,69,71].…”