Abstract
The breast cancer (BC) biomarker HER2 (Human Epidermal Receptor 2) is overexpressed in 25% of BC. Only patients with HER2-positive tumors receive HER2-targeting therapies, like trastuzumab (Herceptin). However, some women with a HER2-negative BC could benefit from trastuzumab. This could be explained by the activation/phosphorylation of HER2 that can be recognized by trastuzumab. The aim of this study is to examine trastuzumab effects on HER2 phosphorylation at tyrosine Y877 (pHER2Y877). HER2 and pHER2Y877 status were evaluated in a cohort of BC patients representative of molecular subtypes distribution (n = 497) and in a series of BC cell lines (n = 7). Immunohistochemistry against pHER2Y877 was performed on tissue micro arrays. Cellular proliferation assays were performed on BC cell lines presenting different combinations of HER2 and pHER2Y877 status and treated with increasing doses of trastuzumab (0–150 μg/ml). The prevalence of pHER2Y877 in this cohort was 6%. Nearly 5% of patients with HER2-negative tumors (n = 406, 82%) overexpressed pHER2Y877. Among triple negative BC patients (n = 39, 8%), 7.7% expressed pHER2Y877. Trastuzumab treatment decreased cell proliferation in HER2−/pHER2Y877+ BC cell lines, to an extent comparable to what occurs in HER2+ cell lines, but did not affect HER2−/pHER2Y877− cell lines. Trastuzumab sensitivity in HER2−/pHER2Y877+ cell line is specific to HER2 tyrosine 877 phosphorylation. Hence, with further confirmation in a bigger cohort, trastuzumab treatment could be envisaged as a treatment option to women presenting with HER2−/pHER2+ tumors, representing more than 1000 BC women in Canada in 2019.
Highlights
According to the Public Health Agency of Canada (PHAC), breast cancer (BC) represents 25% of new cases of cancers and 13% of all cancer deaths in women in 2019
To evaluate pHER2Y877 clinical relevance, pHER2Y877 distribution was established in the BC population, as measured by the HER2Y877 prevalence in the BC patient cohort
Even though there is a significant difference between BT-549 and MDA-MB-231 or JIMT-1 overall in their response to trastuzumab (p
Summary
According to the Public Health Agency of Canada (PHAC), breast cancer (BC) represents 25% of new cases of cancers and 13% of all cancer deaths in women in 2019.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have