Research Papers:

Intratumoral expression of CCR3 in breast cancer is associated with improved relapse-free survival in luminal-like disease

Di-He Gong _, Lei Fan, Hai-Yan Chen, Ke-Feng Ding and Ke-Da Yu

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Oncotarget. 2016; 7:28570-28578. https://doi.org/10.18632/oncotarget.8680

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Di-He Gong1,2,*, Lei Fan1,*, Hai-Yan Chen3, Ke-Feng Ding3, Ke-Da Yu1

1Department of Breast Surgery, Shanghai Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, 200032, P. R. China

2Department of Thyroid and Breast Surgery, Affiliated Cixi Hospital, Wenzhou Medical University, Cixi Zhejiang, 315300, P. R. China

3Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou Zhejiang, 310009, P. R. China

*These authors have contributed equally to this work

Correspondence to:

Di-He Gong, e-mail: [email protected]

Ke-Da Yu, e-mail: [email protected]

Keywords: CCR3, breast cancer, peritumoral, luminal-like, relapse-free survival

Received: December 21, 2015    Accepted: March 28, 2016    Published: April 11, 2016


Purpose: The association chemokine receptor CCR3 with breast cancer subtypes and relapse-free survival is unknown.

Results: The overall expression (either intratumoral or peritumoral) of CCR3 was not associated with tumor size, lymph node status, age, and subtype. When we confined the analysis in samples without peritumoral stromal CCR3 expression, intratumoral expression of CCR3 was associated with breast cancer subtype (P=0.04). Tumors with high expression of CCR3 were more likely to be luminal-like rather than TNBC or HER2-enriched cancers. Moreover, high mRNA expression of CCR3 was related with improved relapse-free survival in luminal-A/B (P<0.001). The subsequent sensitivity analysis using the systemically untreated patients confirmed that higher mRNA expression of CCR3 was a robust prognostic factor for luminal-A (P=0.0025) and luminal-B (P=0.088), but not for HER2-enriched (P=0.21) and TNBC (P=0.86). In the independent cohort, the positive association between increased expression of CCR3 and improved distant relapse-free survival was also observed.

Methods: We determined the expression level of CCR3 in 150 cases with breast cancer by using immunohistochemistry (IHC) assay, for both intratumoral and peritumoral stroma, and investigated the effect of CCR3 expression on relapse-free survival according to subtype using cases from publicly available datasets, in the whole group (N=3557) and in the patients without adjuvant systemic treatment (N=1005), respectively. Moreover, the survival outcomes were validated in another independent cohort including 508 breast cancer patients treated with neoadjuvant chemotherapy.

Conclusions: Our data indicate that intratumoral expression of CCR3 in breast cancer is associated with improved relapse-free survival in patients with luminal-like disease.

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