title: CD24 Ala57Val polymorphism predicts pathologic complete response to sequential anthracycline- and taxane-based neoadjuvant chemotherapy for primary breast cancer.
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.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital, University of Heidelberg and National Center for Tumor Diseases, Voßstr. 9, 69115 Heidelberg, Germany. Frederik.Marme@med.uni-heidelberg.de
authors.forename: Frederik
authors.initials: F
authors.lastname: Marmé
authors.forename: Wiebke
authors.initials: W
authors.lastname: Werft
authors.forename: Anne
authors.initials: A
authors.lastname: Walter
authors.forename: Sascha
authors.initials: S
authors.lastname: Keller
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
authors.forename: Peter
authors.initials: P
authors.lastname: Sinn
authors.forename: Sarah
authors.initials: S
authors.lastname: Hug
authors.forename: Christof
authors.initials: C
authors.lastname: Sohn
authors.forename: Niko
authors.initials: N
authors.lastname: Bretz
authors.forename: Gerhard
authors.initials: G
authors.lastname: Moldenhauer
authors.forename: Christian
authors.initials: C
authors.lastname: Rupp
authors.forename: Anne-Kathleen
authors.initials: AK
authors.lastname: Rupp
authors.forename: Mikhail Y
authors.initials: MY
authors.lastname: Biakhov
authors.forename: Alberto
authors.initials: A
authors.lastname: Bottini
authors.forename: Kay
authors.initials: K
authors.lastname: Friedrichs
authors.forename: V A
authors.initials: VA
authors.lastname: Khailenko
authors.forename: Georgiy M
authors.initials: GM
authors.lastname: Manikhas
authors.forename: Amparo
authors.initials: A
authors.lastname: Ruiz
authors.forename: Pedro
authors.initials: P
authors.lastname: Sánchez-Rovira
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Segui
authors.forename: Carlos
authors.initials: C
authors.lastname: Villena
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Peter
authors.initials: P
authors.lastname: Altevogt
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
mesh_terms: D019943:Amino Acid Substitution; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051927:CD24 Antigen / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005838:Genotype; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D000068437:Pemetrexed; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; D005971:Glutamates; D043823:Taxoids; D000068437:Pemetrexed; D000077143:Docetaxel; D006147:Guanine; D004317:Doxorubicin; D003520:Cyclophosphamide; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human