Background: Chemokines (chemotactic cytokines) are key regulators of the immune response, attracting immune cells to sites of inflammation, activating adhesion molecules, promoting extravasation and influencing T-cell subset polarization. Recent clinical data has shown a strong correlation between tumor infiltrating lymphocytes (TILs) and response to T therapy in HER2+ BC while the combination of chemotherapy, T and L has proven superior to chemotherapy and T alone in the neo-adjuvant setting (NeoALTTO). This preliminary study examines the levels of 40 circulating chemokines in 32 HER2+ BC patient plasma samples from ICORG 10-05 (neo-adjuvant DCT, DCL or DCTL) to investigate differences in chemokine profiles between treatment arms and patient's response to treatment.

Methods: Pre-treatment blood samples were collected before commencement of chemotherapy; post-treatment samples were collected two weeks prior to surgery. All patients received G-CSF concurrent with treatment. A panel of 40 chemokines and chemokine-associated cytokines were assessed by Luminex xMAP multiplex assay. Matched patient samples were run in single replicates and analysed together (n=32) or by comparing DCT (n=12) and DCTL (n=14) treatment arms (using a paired Mann-Whitney test and adjusting for multiple testing using Bonferroni correction). DCL (n=6) was omitted from the arm comparison due to low numbers. In addition, principle components analysis (PCA) was used to explore any trends within the data based on patient response (pathological complete response (pCR, n=15), partial response (PR, n=12), and non-response (NR, n=4)). 12 non-age matched healthy volunteer controls were also included in the PCA.

Results: PCA shows a clear separation between pre- and post-treatment samples. 30 of the 40 chemokines examined were significantly differentially expressed (adjusted p-value of <0.05) post-treatment across all treatment arms. When comparing DCT and DCTL, nine chemokines were significantly altered post-therapy in both arms with two chemokines, CCL24 (p=0.039) and IL-16 (p=0.039), increased in DCT only and ten chemokines, CCL11 (p=0.009), CX3CL1 (p=0.004), CXCL1 (p=0.009), CCL1 (p=0.024), IL-2 (p=0.043), IL-6 (p=0.034), IL-8 (p=0.004), CXCL11 (p=0.004), CXCL16 (p=0.004) and TNF-alpha (p=0.004) altered in DCTL only. PCA identified no trend between pre- and post-treatment chemokine levels and response.

Conclusions: DCT and DCTL produce statistically different alterations in the plasma chemokine profiles of HER2+ BC patients. Pre- or post-treatment levels of the chemokines examined are not collectively predictive of patient response to treatment. Further work is required to elucidate the relevance of DCT- and DCTL-specific chemokine alterations to response.

Citation Format: Collins DM, Madden SF, Gaynor N, Gallagher WM, O'Donovan N, Crown J. Plasma chemokine profile of HER2+ breast cancer (BC) patients treated with docetaxel (D) and carboplatin (C) in combination with trastuzumab (T) and/or lapatinib (L) in the neo-adjuvant setting [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-27.