The chemokine CCL5 as a potential prognostic factor predicting disease progression in stage II breast cancer patients.
OBJECTIVE
The aim of this study was to determine the prognostic value of the chemokine CCL5, considered as a promalignancy factor in breast cancer, in predicting breast cancer progression and to evaluate its ability to strengthen the prognostic significance of other biomarkers.


METHODS
The expression of CCL5, alone and in conjunction with estrogen receptor (ER)-alpha, ER-beta, progesterone receptor (PR), and HER-2/neu (ErbB2), was determined in breast tumor cells by immunohistochemistry. The study included 142 breast cancer patients, including individuals in whom disease has progressed.


RESULTS
Using Cox proportional hazard models, univariate analysis suggested that, in stage I breast cancer patients, CCL5 was not a significant predictor of disease progression. In contrast, in stage II patients, the expression of CCL5 (CCL5(+)), the absence of ER-alpha (ER-alpha(-)), and the lack of PR expression (PR(-)) increased significantly the risk for disease progression (P = 0.0045, 0.0041, and 0.0107, respectively). The prognostic strength of CCL5, as well as of ER-alpha(-), improved by combining them together (CCL5(+)/ER-alpha(-): P = 0.0001), being highly evident in the stage IIA subgroup [CCL5(+)/ER-alpha(-) (P = 0.0003); ER-alpha(-) (P = 0.0315)]. In the stage II group as a whole, the combinations of CCL5(-)/ER-alpha(+) and CCL5(-)/PR(+) were highly correlated with an improved prognosis. Multivariate analysis indicated that, in stage II patients, ER-alpha and CCL5 were independent predictors of disease progression.


CONCLUSIONS
CCL5 could be considered as a biomarker for disease progression in stage II breast cancer patients, with the CCL5(+)/ER-alpha(-) combination providing improved prediction of disease progression, primarily in the stage IIA subgroup.
Yaal-Hahoshen
Neora
N
Department of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Shina
Sima
S
Leider-Trejo
Leonor
L
Barnea
Itay
I
Shabtai
Esther L
EL
Azenshtein
Elina
E
Greenberg
Iulia
I
Keydar
Iafa
I
Ben-Baruch
Adit
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D018946:Chemokine CCL5 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis
D014408:Biomarkers, Tumor; C483024:CCL5 protein, human; D018946:Chemokine CCL5