Delay to Formalin Fixation (Cold Ischemia Time) Effect on Breast Cancer Molecules

Objectives: The gold standard of examining breast biomarkers, including estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2)/Ki-67, is to perform these assays on formalin-fixed, paraffin-embedded tissue. However, preanalytical variables may confound these assays. One of these factors is delay to formalin fixation (DFF). The purpose of this review is to evaluate each study that investigated the effect of DFF on breast biomarkers and other molecules.

Methods: Thirteen primary research articles were identified by the literature search. The credibility of the studies was judged based on the degree of controlling other confounding factors. Nine studies had a prospective design with a high number of controlled variables.

Results: Most of the studies concluded that DFF had an effect on ER/PR/HER2. Some of these studies showed that DFF had negative effect on other markers used either clinically or for research purposes.

Conclusions: The vast majority of the studies agree that DFF has negative effect on breast biomarkers.