Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial

Poor survival outcomes in HER2-positive breast cancer patients with low-grade, node-negative tumours

“…The persistence of a reduction in survival in our HER2positive or ER-positive subgroup despite endocrine therapy is in keeping with the recent trans-ATAC (Arimidex, Tamoxifen, Alone or in Combination) and BIG1 -98 analysis based on HER2 status (Ranganathan et al, 2007) (Rasmussen et al, 2008) and suggests that we cannot rely solely on adjuvant endocrine therapy (tamoxifen or aromatase inhibitor) in these largely ER-positive patients.…”

Breast cancer cells can switch between estrogen receptor α and ErbB signaling and combined treatment against both signaling pathways postpones development of resistance

“…In concert, development of acquired resistance to antiestrogen therapy is often accompanied with changes resulting in increased signaling through the ErbB system, e.g., increased expression of ligands, receptors, or downstream effector molecules [5][6][7][8][9][10][11]15]. In the clinic, response to endocrine therapy is found to be reduced in patients with high expression of TGFa or EGFR [43,44], and ERa/ErbB2 positive tumors are less sensitive to both antiestrogen and aromatase inhibitor therapy than ERa positive/ErbB2 negative tumors [23]. In our cell culture model system comprising MCF-7 breast cancer cell lines with acquired resistance toward treatment with the antiestrogen fulvestrant, changes in the ErbB signaling pathway were evident at ligand, receptor, and downstream effector levels [8,11].…”

“…Furthermore, preclinical data have suggested that increased growth factor expression and signaling through the ErbB receptors or downstream effectors may repress ERa expression and function [16][17][18][19], potentially making breast cancer cells less sensitive to endocrine therapy. Also, clinical data have indicated an inverse relationship between expression of at least the EGFR and ErbB2 receptors with ERa and their overexpression has been correlated to decreased antiestrogen sensitivity [20][21][22][23].…”

High concordance between HercepTest immunohistochemistry and ERBB2 fluorescence in situ hybridization before and after implementation of American Society of Clinical Oncology/College of American Pathology 2007 guidelines

“…3 Subsequent studies, however, have displayed a lower percentage of HER2-positive cases, from 15-25% of breast cancers to as low as 7%. 22,23 A small number of our cases were rated as negative by HercepTest immunohistochemistry and yet demonstrated amplification by PathVysion fluorescence in-situ hybridization, thus considered as a false-negative result. Using a stepwise algorithm of performing immunohistochemistry first, then subsequent fluorescence in-situ hybridization testing based on immunohistochemistry results, a small percentage of samples would inevitably be scored as falsely negative, thereby inappropriately excluding these patients from trastuzumab (Herceptin) therapy.…”