Predictive significance of DNA damage and repair biomarkers in @entity0 XXXX treated with neoadjuvant chemotherapy: An exploratory analysis.

@entity15126 @entity1 @entity0 @entity5 @entity23902 @entity5282 @entity6714 @entity9516
UNASSIGNED: Response of @entity5 cells to chemotherapy-induced DNA damage is regulated by the ATM- @entity9516 and @entity15126 - @entity23902 pathways. We investigated the association between phosphorylated @entity6714 ( @entity6714 ), a marker of DNA double-strand breaks that trigger the ATM- @entity9516 cascade, and phosphorylated @entity23902 (pChk1), with pathological complete response (pCR) in @entity0 ( @entity0 ) @entity1 treated with neoadjuvant chemotherapy. @entity6714 and pChk1 were retrospectively assessed by immunohistochemistry in a series of pretreatment biopsies related to 66 @entity1 . In fifty-three @entity5 @entity5282 status was negative in both the diagnostic biopsies and @entity5 , whereas in 13 cases there was a slight @entity5282 expression that changed after chemotherapy. Internal validation was carried out. In the entire cohort elevated levels of @entity6714 , but not pChk1, were associated with reduced pCR rate (p = 0.009). The association tested significant in both uni- and multivariate logistic regression models (OR 4.51, 95% CI: 1.39-14.66, p = 0.012, and OR 5.07, 95% CI: 1.28-20.09, p = 0.021, respectively). Internal validation supported the predictive value of the model. The predictive ability of @entity6714 was further confirmed in the multivariate model after exclusion of @entity5 that underwent changes in @entity5282 status during chemotherapy (OR 7.07, 95% CI: 1.39-36.02, p = 0.018). Finally, in residual diseases a significant decrease of @entity6714 levels was observed (p < 0.001). Overall, @entity6714 showed ability to predict pCR in @entity0 and deserves larger, prospective studies.
