The effect of prolonged cold ischemia time on breast cancer biomarker expression after neoadjuvant chemotherapy

Abstract

Prolonged cold ischemia time (CIT) and neoadjuvant chemotherapy (NACT) can each independently impact the expression of breast cancer-related biomarkers, but their combined effects are not well studied. Herein, we assessed whether prolonged CIT has a higher modulatory effect on post-NACT biomarker expression in breast cancer specimens than in otherwise similar but non-NACT specimens. Our study cohort included 334 biopsy/resection breast cancer specimen pairs in which immunohistochemistry (IHC for estrogen receptor [ER], progesterone receptor [PR], HER2) and HER2 FISH had been performed on both specimens. These included 209 pairs with a post-NACT resection (NACT[+]), and 125 pairs unassociated with NACT (NACT[-]). Each group was subclassified into prolonged CIT (>1 hr; CITp) and non-prolonged CIT (≤1 hr, CITnp). NACT[+]/CITp (n = 125) and NACT[-]/CITp (n = 84) subgroups showed no statistically significant differences regarding the frequency of biopsy-to-resection change in the final result [i.e. positive versus negative] for any of the 4 biomarkers. Similarly, the NACT[+]/CITp and NACT[+]/CITnp subgroups showed no significant differences regarding the percentage of cases with any biopsy-to-resection change in final result for ER, HER2 (IHC) and HER2 (FISH). For PR, a biopsy-to-resection change in status was more commonly observed in CITnp (44.1 %) as compared to the CITp (19.2 %) subgroup (p = 0.02). In summary, we found no conclusive evidence that prolonged CIT has a more significant modulatory effect on biomarker expression in post-NACT breast cancer resection specimens than their otherwise comparable (i.e. NACT[-], CITp) counterparts regarding the final test result, which suggests that post-NACT specimens do not require more stringent CIT-related handling requirements than NACT[-] specimens.