Could HER2 Amplification Aid in the Prognosis of HER2-Positive Breast Cancer?

The presence of HER3 expression and a high HER2/CEP17 ratio distinguish a group of invasive HER2-positive ductal breast cancer patients who have a worse prognosis, according to a new study.

Trastuzumab can be effective in some HER2-positive breast cancer patients, but response rates of only 15%–26% suggest the presence of mechanisms that determine trastuzumab resistance, wrote study authors led by Agnieszka Adamczyk, MD, of the Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology in Krakow, Poland. The factors affecting resistance could include overexpression of the MUC4 protein, activation of HER2 signaling cascades, and downregulation of PTEN protein expression.

The new study’s goal was to analyze the relationship between HER2 status-based on the HER2/CEP17 ratio, gene copy number, and polysomy of chromosome 17-and factors related to trastuzumab resistance. They included a group of 117 patients with invasive ductal breast cancer overexpressing HER2 who underwent surgery between 2007 and 2014; the results were published in Oncotargets and Therapy.

The median age of patients in the study was 56 years, and all received adjuvant trastuzumab therapy; those with estrogen/progesterone receptor–positive disease also received hormone therapy.

Overexpression of HER2 protein (IHC 3+ based on immunohistochemistry analysis) was found to be associated with higher HER2 copy number (mean per cell of 19.53 vs 7.32 for IHC 2+; P < .001), as well as with HER2/CEP17 ratio (7.87 for IHC 3+ vs 3.17 for IHC 2+; P < .001). Estrogen receptor negativity also corresponded with both those measures (P < .001). Tumors with chromosome 17 polysomy had higher HER2 copy numbers per cell than those in which polysomy was absent (mean per cell of 19.20 vs 15.53; P = .026), but they also had a lower HER2/CEP17 ratio (4.62 vs 7.53; P < .001).

A survival analysis of the cohort covered a mean follow-up period of 54.8 months. Patients with HER3 immunonegativity or with a low HER2/CEP17 ratio (≤ 4) had a 100% metastasis-free survival rate. Patients with a ratio of 4 or higher had a metastasis-free survival rate of 85.5%.

“Although the degree of HER2 amplification might not be a decisive factor for survival of HER2-positive breast cancer patients, it probably could be analyzed with other parameters and help in distinguishing patients with worse prognosis,” the authors concluded.