Investigation of HER-2 status, treatment response and survival analysis in cervical cancer patients

Abstract

Anti-HER2 therapy has shown benefit in breast and gastric cancers that over-express HER2; therefore, it is critical to determine whether HER2 is over-expressed and amplified in cervical cancer with current FDA-approved tests, as previous works have reported frequencies of over-expression varying from 0% to 77%. We analyzed 100 consecutive patients starting in January 2013. Patients were previously untreated and diagnosed with locally advanced cervical cancer. They received chemoradiation as definitive treatment. We analyzed their primary tumors with HercepTest and HER-2/neu FISH probe, observing a strong adherence to the testing and reporting recommendations for HER2 testing in breast cancer by the American Society of Clinical Oncology. Among 100 patients, accrued 88 had both tests performed. We found 26 (29.5%) FISH-positive cases. HercepTest scores rating 0+, 1+, 2+, and 3+ were observed in 65.3%, 11.5%, 7.6% and 15.3% in the 26 FISH-positive. There was no concordance between the results of both tests using Cohen´s Kappa statistics, neither correlation between FISH status with age, FIGO stage, and response. FISH-positive patients had a non-statistical significant trend for worst 4-year survival. The HER2 protein is over-expressed in only a small subset of invasive cervical cancer as analyzed by Hercept test. Unexpectedly, HER2 gene amplification occurred in around 29.5% of cases. We stress that analyzed HER2 status with the validated methods for the procedures and reports used for breast cancer. Our results must be seen with caution and must encourage further testing in a higher number of patients and different populations to confirm our findings.