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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2012

01-04-2012 | Clinical Trial

CD24 Ala57Val polymorphism predicts pathologic complete response to sequential anthracycline- and taxane-based neoadjuvant chemotherapy for primary breast cancer

Authors: Frederik Marmé, Wiebke Werft, Anne Walter, Sascha Keller, Xiaoli Wang, Axel Benner, Barbara Burwinkel, Peter Sinn, Sarah Hug, Christof Sohn, Niko Bretz, Gerhard Moldenhauer, Christian Rupp, Anne-Kathleen Rupp, Mikhail Y. Biakhov, Alberto Bottini, Kay Friedrichs, V. A. Khailenko, Georgiy M. Manikhas, Amparo Ruiz, Pedro Sánchez-Rovira, Armando Santoro, Miguel A. Segui, Carlos Villena, Peter Lichter, Glen Kristiansen, Peter Altevogt, Andreas Schneeweiss

Published in: Breast Cancer Research and Treatment | Issue 3/2012

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Abstract

Overexpression of CD24 is an independent prognostic factor for breast cancer. Recently, two polymorphisms in the CD24 gene were linked to disease risk and progression in autoimmune diseases. Here, we evaluated the clinical relevance of these polymorphisms with respect to their potential to predict a pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) for primary breast cancer (PBC), one of the strongest prognostic factors in this setting. A total of 257 patients were randomized to either doxorubicin/cyclophosphamide (AC) or doxorubicin/pemetrexed (AP), both followed by docetaxel (Doc) as NCT for T2-4 N0-2 M0 PBC as part of an international, multicenter, randomized phase II trial. CD24 polymorphisms were analyzed on germ line DNA and correlated with clinicopathologic variables and pCR. No significant associations were found between either of the polymorphisms and any of the clinicopathologic variables. In a multivariate analysis, CD24 Val/Val genotype was the only significant predictor of pCR (OR: 4.97; P = 0.003). The predictive potential was significant in both treatment arms and in the hormone receptor–positive subgroup. There was no correlation between CD24 3′UTR (TG/Del) genotype and pCR. We did not observe any association between CD24 genotype and CD24 protein expression or in vitro chemosensitivity, but there was a significant correlation between CD24 Val/Val and intratumoral lymphocyte aggregates. In conclusion, CD24 Ala/Val SNP is a strong and independent predictor of pCR after NCT for PBC and may affect immune functions rather than tumor characteristics. Further evaluation of the CD24 function and validation of its predictive potential are clearly warranted.
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Metadata
Title
CD24 Ala57Val polymorphism predicts pathologic complete response to sequential anthracycline- and taxane-based neoadjuvant chemotherapy for primary breast cancer
Authors
Frederik Marmé
Wiebke Werft
Anne Walter
Sascha Keller
Xiaoli Wang
Axel Benner
Barbara Burwinkel
Peter Sinn
Sarah Hug
Christof Sohn
Niko Bretz
Gerhard Moldenhauer
Christian Rupp
Anne-Kathleen Rupp
Mikhail Y. Biakhov
Alberto Bottini
Kay Friedrichs
V. A. Khailenko
Georgiy M. Manikhas
Amparo Ruiz
Pedro Sánchez-Rovira
Armando Santoro
Miguel A. Segui
Carlos Villena
Peter Lichter
Glen Kristiansen
Peter Altevogt
Andreas Schneeweiss
Publication date
01-04-2012
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2012
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-011-1759-9

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