Dkk1 as a Prognostic Marker for Neoadjuvant Chemotherapy Response in Breast Cancer Patients

Cancers (Basel). 2024 Jan 18;16(2):419. doi: 10.3390/cancers16020419.

Abstract

Purpose: To investigate the role of Dkk1 as a predictor of response to NACT in BC patients.

Methods: This retrospective monocentric study included 145 women who had undergone NACT followed by breast surgery. Dkk1 protein expression was assessed using immunohistochemistry staining in core needle biopsies and mammary carcinoma specimens.

Results: Dkk1 levels were lower in treated BC tumours than in untreated tumours. The outcomes of 68 matched pre- and post-therapy tissues showed that Dkk1 levels in mammary carcinoma tissues were significantly predicted by levels in core needle biopsies and that Dkk1 expression was reduced in 83% of cases. Smaller cT stage, positive Her2 expression, and decreased Dkk1-IRS in core needle biopsy tissues were all independent predictors of regression grade (R4), according to Sinn. However, the percentage of Dkk1 expression differences prior to and following NACT had no effect on PFS or OS.

Conclusions: In this study, we demonstrated for the first time that Dkk1 could be identified as an independent predictor of NACT response in BC patients, particularly those with TNBC. Further research with a multicentric expanded (pre-/post-therapy) sample set and better-defined populations in terms of molecular subtypes, therapy modality, and long-term follow-up is recommended to obtain more solid evidence.

Keywords: Dickkopf-1; breast cancer; immunohistochemistry; neoadjuvant therapy; personalised treatment; therapy response.

Grants and funding

This work was supported by the Department of Gynaecology, Obstetrics and Reproductive Medicine at the University Medical School of Saarland.