Relationship between gene status and selected potential biological features related to trastuzumab resistance and its influence on survival of breast cancer patients undergoing trastuzumab adjuvant treatment.

BACKGROUND

The aim of the study was to investigate if parameters associated with human epidermal growth factor receptor type 2 () status ( gene copy number, ratio or polysomy of chromosome 17) are related to various biological features potentially responsible for trastuzumab resistance (PTEN, IGF-1R, MUC4, EGFR, HER3, HER4, and mutation status of ) as well as their influence on survival of HER2-positive breast cancer patients treated with adjuvant chemotherapy and trastuzumab.

PATIENTS AND METHODS

The investigated group consisted of 117 patients with invasive ductal breast cancer (T≥1, N≥0, M0) with overexpression of HER2, who underwent radical surgery between 2007 and 2014. Status of ER, PR, and HER2 expression was retrieved from patients' files. gene copy number was investigated by fluorescence in situ hybridization using PathVysion HER-2 DNA Probe Kit II. Expression of PTEN, IGF-1R, MUC4, EGFR, HER3, and HER4 was assessed immunohistochemically on formalin-fixed paraffin-embedded tissue sections. mutation status was determined by qPCR analysis.

RESULTS

Overexpression of HER2 protein (IHC 3+) and ER negativity corresponded to higher 2 copy number and ratio (.<0.001). Tumors with polysomy were characterized by higher 2 gene copy number but lower ratio (<0.026, <0.001). Patients with tumors featuring HER3 immunonegativity or low ratio (#4) were characterized by 100% metastasis-free survival (.=0.018, =0.062).

CONCLUSION

Presence of both unfavorable factors, ie, HER3 expression and high ratio, allowed to distinguish a group of patients with worse prognosis (.=0.001).