Abstract P4-06-26: High expressions of CXCR4 and CCR5 are associated with poor prognosis in triple negative breast cancer resistant to neoadjuvan chemotherapy
Authors: Cabioglu N , Onder S , Oner G , Karatay H , Tukenmez M , Muslumanoglu M , Igci A , Dinççag A , Aydiner A , Saip P , Ozmen V , Yavuz E 
Published: May 2019

Background: Novel systemic therapies are under investigation for patients with triple negative breast cancer who are resistant to neoadjuvant chemotherapy or having a partial response to neoadjuvant chemotherapy. Immune check point inhibition or blocking other immunologic markers such as chemokine receptors might be alternative pathways for these chemotherapy-resistant patients. Therefore, we investigated various immune check point receptor expressions along with different chemokine receptors.

Method:

Expressions of immunological markers were examined immunohistochemically by staining archival tissue of mastectomy specimen (n=56) using specific monoclonal antibodies for PDL-1 (Ventana SP263 clone kit), CXCR4, CXCR5, CCR5, CCR7, CD73, and CD155. PDL-1 positivity was defined as membranous staining &gt;1% in either tumor and /or stromal lymphocytes, whereas positivity of chemokine receptors and CD155 and CD73 were considered as cytoplasmic staining &gt;50% and &gt;5%, and &gt;1%, respectively.

Results: Median age was 47 (24-76) years. Of those, 31 were clinically T3-4 (55%), whereas almost all of them were N1-3 (96.4%) before neoadjuvant chemotherapy. All patients received anthracyclines&paclitaxel containing regimens, whereas 3 patients received additional carboplatin before definitive surgery.

Of those, 30 patients (58%) were detected to be positive for PDL1 in tumor site and intratumoral lmyphocytes, whereas CXCR5 (41.1%, 23/56) , CCR5 (48.2%, 27/56), CCR7 (41.1%, 23/56), CD155 (30/56, 58%) and CD73 (44.6%, 25/56) were found to be highly expressed in tumors. However, 12.5% of patients have shown high expression of CXCR4. Patients with CXCR5, CCR5, CCR7, CD73, CD155 positivity were more likely found to give a worse chemotherapy response as measured by “Residual Cancer Burden Index”.

Table 1.Associations between MD Anderson Residual Cancer Burden Index and Immunological Biomarker ExpressionsTumor characteristicsClass IClass 2&3P-valueCXCR4-negative8.3%91.7%0.999CXCR4-positive0%100% CXCR5-negative12.5%87.5%0.131CXCR5-positive0%100% CCR5-negative14.3%85.7%0.111CCR5-positive0%100% CCR7-negative12.5%87.5%0.131CCR7-positive0%100% CD73-negative13.3%86.70.117CD73-positive0%100% CD155-negative16%84%0.037CD155-positive0%100% PDL1-negative4.895.20.999PDL1-positive3.396.7% 

Median follow-up time was 36 months (7-177). Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were found to be decreased in patients with CXCR4 (DFS: negative, 55% vs positive, 23%; p= 0.079 and DSS: negative, 52% vs positive, 23%; p=0.034) and CCR5 positivity(DFS: negative, 63.5% vs positive, 26%; p= 0.037 and DSS: negative, 61% vs positive, 25%; p=0.047), while no significant difference could be found in DFS and DSS rates in regards to PDL1, CXCR5, CCR7, CD73 and CD155 positivity.

Conclusion: These results demonstrate that PDL-1, CD73, CD155 and chemokine receptors are highly expressed in patients with partial response to neoadjuvant chemotherapy. Furthermore, expressions of CXCR4 and CCR5 were found to be associated with poor prognosis in this cohort with triple negative breast cancer resistant to chemotherapy that would justify an addititional chemokine receptor inhibitor therapy.

Citation Format: Cabioglu N, Onder S, Oner G, Karatay H, Tukenmez M, Muslumanoglu M, Igci A, Dinççag A, Aydiner A, Saip P, Ozmen V, Yavuz E. High expressions of CXCR4 and CCR5 are associated with poor prognosis in triple negative breast cancer resistant to neoadjuvan chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-26.