Breast cancer, locally advanced Poster lunch Poster Display session

81P - Quantitation of cell loss in breast cancer during neoadjuvant treatment (NACT) assessed by serum thymidine kinase protein concentration (sTK1) (ID 1693)

Presentation Number
81P
Presentation Topic
Breast cancer, locally advanced
Lecture Time
13:00 - 13:00
Speakers
  • B. Tribukait
Authors
  • B. Tribukait
  • K. Jagarlamudi
  • J. Bergh
  • T. Hatschek
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

NACT of early breast cancer (BC) is intended to facilitate less extensive surgery by downstaging and provides the opportunity to study tumor response due to treatment. TK1 has a key function in DNA synthesis and repair responsible for maintaining the nucleoid pool balance by salvage and recycle thymidine from extracellular sources. Normally, TK1 is synthesized during S-phase, inactivated at mitosis and not leaked in connection with cell death. In contrast, release of TK1 into blood by necrosis or apoptosis is typical in malignancies.

Methods

We quantified cell loss using TK210 ELISA® for serial measurements of sTK1 in blood from 145 BC patients undergoing epirubicin/docetaxel +bevacizumab NACT therapy. sTK1 was related to clinical/radiological response after cycle (Cy) 2, 4 and 6, pathologic response, and disease free survival.

Results

Base-line sTK1 3-doubles 48h after treatment to plateau levels but declines during the 3 weeks rest between courses. sTK1 measured after treatment arrest periods correlated, after 4 cycles of treatment, significantly with clinical/radiological response during treatment and pathologic response at surgery. Surprisingly, the 48 h plateau values are highest in pT0, followed by pT3, pT2 and lowest in pT1. Disease free survival (median follow-up 49 mo.) ranged between 29.7% in pT0 and 5.7% in pT1 and is significantly related to sTK1.

Conclusions

Proliferation and cell loss are responsible for tumor growth and response to therapy. By now, no quantitation methods for cell loss are available. In this study TK1 has been proven to be a significant predictor of treatment response in NACT. sTK1 is a promising method for treatment related response and clinical drug development.

Clinical trial identification

EudraCT Number: 2007-005858-23

Legal entity responsible for the study

Karolinska Institute

Funding

Karolinska Institute

Disclosure

B. Tribukait: The author has stocks in AroCell. K.K. Jagarlamudi: I am working at AroCell AB.

All other authors have declared no conflicts of interest.

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