TY - JOUR
T1 - Improved outcome of high-risk early HER2 positive breast cancer with high CXCL13-CXCR5 messenger RNA expression
AU - Razis, Evangelia
AU - Kalogeras, Konstantine T.
AU - Kotoula, Vassiliki
AU - Eleftheraki, Anastasia G.
AU - Nikitas, Nikitas
AU - Kronenwett, Ralf
AU - Timotheadou, Eleni
AU - Christodoulou, Christos
AU - Pectasides, Dimitrios
AU - Gogas, Helen
AU - Wirtz, Ralph M.
AU - Makatsoris, Thomas
AU - Bafaloukos, Dimitrios
AU - Aravantinos, Gerasimos
AU - Televantou, Despina
AU - Pavlidis, Nicholas
AU - Fountzilas, George
PY - 2012/6
Y1 - 2012/6
N2 - Background: Chemokines are important in cell migration and are thought to play a key role in metastasis. We explored the prognostic significance of C-X-C ligand-motif (CXCL) 12, CXCL13, and receptor (CXCR) 5 on disease-free survival (DFS) and overall survival (OS) in early breast cancer. Methods: A total of 595 patients at high risk for early breast cancer were treated in a 2-arm trial (HE10/97) with dose-dense sequential epirubicin followed by cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) with or without paclitaxel. RNA was extracted from 321 formalin-fixed paraffin-embedded primary tumor tissue samples and quantitative reverse-transcriptase polymerase chain reaction was used to assess messenger RNA (mRNA) expression of CXCL12, CXCL13, and CXCR5; estrogen receptor; progesterone receptor (PgR); microtubule-associated protein tau and human epidermal growth factor receptor 2 (HER2). Results: CXCL13 and CXCR5 were found to be negatively associated with estrogen receptor and microtubule-associated protein tau mRNA expression and with dense lymphocytic infiltration, and were positively associated with nuclear grade. Only CXCL13 was positively associated with HER2. Multivariate analysis revealed an association between high CXCL13 mRNA expression and improved DFS (hazard ratio [HR] 0.48 [95% CI, 0.25-0.90]; Wald, P =.023) but not OS; whereas high CXCL12 expression was significantly associated with increased OS (HR 0.53 [95% CI, 0.33-0.85]; Wald, P =.009). In the HER2 mRNA overexpressing subgroup, high CXCL13 mRNA expression was associated with improved DFS (P <.001), whereas high CXCR5 was associated with increased DFS and OS (P =.004 and P =.049, respectively). Conclusions: The CXCL13-CXCR5 axis is associated with classic determinants of poor prognosis, such as high grade, hormone receptor negativity, and axillary node involvement. Interestingly, this chemokine axis seems to be strongly associated with improved outcome in patients with HER2+ disease.
AB - Background: Chemokines are important in cell migration and are thought to play a key role in metastasis. We explored the prognostic significance of C-X-C ligand-motif (CXCL) 12, CXCL13, and receptor (CXCR) 5 on disease-free survival (DFS) and overall survival (OS) in early breast cancer. Methods: A total of 595 patients at high risk for early breast cancer were treated in a 2-arm trial (HE10/97) with dose-dense sequential epirubicin followed by cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) with or without paclitaxel. RNA was extracted from 321 formalin-fixed paraffin-embedded primary tumor tissue samples and quantitative reverse-transcriptase polymerase chain reaction was used to assess messenger RNA (mRNA) expression of CXCL12, CXCL13, and CXCR5; estrogen receptor; progesterone receptor (PgR); microtubule-associated protein tau and human epidermal growth factor receptor 2 (HER2). Results: CXCL13 and CXCR5 were found to be negatively associated with estrogen receptor and microtubule-associated protein tau mRNA expression and with dense lymphocytic infiltration, and were positively associated with nuclear grade. Only CXCL13 was positively associated with HER2. Multivariate analysis revealed an association between high CXCL13 mRNA expression and improved DFS (hazard ratio [HR] 0.48 [95% CI, 0.25-0.90]; Wald, P =.023) but not OS; whereas high CXCL12 expression was significantly associated with increased OS (HR 0.53 [95% CI, 0.33-0.85]; Wald, P =.009). In the HER2 mRNA overexpressing subgroup, high CXCL13 mRNA expression was associated with improved DFS (P <.001), whereas high CXCR5 was associated with increased DFS and OS (P =.004 and P =.049, respectively). Conclusions: The CXCL13-CXCR5 axis is associated with classic determinants of poor prognosis, such as high grade, hormone receptor negativity, and axillary node involvement. Interestingly, this chemokine axis seems to be strongly associated with improved outcome in patients with HER2+ disease.
KW - Chemokines
KW - CXCL12
KW - CXCL13
KW - CXCR5
KW - Estrogen receptor
KW - Human epidermal growth factor receptor 2
KW - Progesterone receptor
UR - http://www.scopus.com/inward/record.url?scp=84861111629&partnerID=8YFLogxK
U2 - 10.1016/j.clbc.2012.03.006
DO - 10.1016/j.clbc.2012.03.006
M3 - Article
C2 - 22607768
AN - SCOPUS:84861111629
SN - 1526-8209
VL - 12
SP - 183
EP - 193
JO - Clinical Breast Cancer
JF - Clinical Breast Cancer
IS - 3
ER -