Abstract P2-02-12: Association of inflammatory and tumor markers with circulating tumor cells in metastatic breast cancer
Authors: Lohmann AE , Chang M , Dowling RJO , Ennis M , Amir E , Elser C , Brezden-Masley C , Vandenberg T , Lee E , Fazae K , Stambolic V , Goodwin PJ 
Published: May 2016

Background: Circulating tumor cells (CTCs) are associated with prognosis in metastatic breast cancer (BC). We evaluated the association of inflammatory/tumor markers and CTCs in women with progressing metastatic breast cancer prior to commencing a new line of systemic therapy.

Methods: From February 2013 to April 2015, 96 patients with metastatic BC about to start a new treatment (due to progression), without current diabetes or use of anti-inflammatory agents, were recruited from four Ontario cancer hospitals. Women provided fasting blood for inflammatory and tumor markers and CTC measurement; CTCs were assayed within 72 hours of collection using CellSearch. Blood was frozen at -80C until assays were performed in a single batch (C-reactive protein (CRP), IL-6, PAI-1, Ca15-3, Ca125, VEGF, TNFa). Associations of CTCs with blood factors were evaluated using Pearson correlation coefficients after transforming the variables to normality. For CTCs the transformation log(x+0.5) was used. Associations with categorical variables were tested using one-way analysis of variance. P values &lt;0.05 were significant.

Results: Median age of patients was 60.5 years, 87 (90.6%) were post-menopausal, 83 (86.5%) had hormone receptor positive BC, 16 (16.7%) HER2 positive BC, 10 (10.4%) triple negative; 75 (78.1%) grade II/III. At the time of CTC measurement, bone, lung, liver and brain metastases were present in 79%, 44%, 40% and 6% of patients respectively, with 54%, 37%, 35% and 3% having progression at these sites respectively. PAI-1 and CA15-3 exceeded the limit of the assay in 11 and 5 cases respectively (the upper limit of the assay was used in the analysis). 33.4% of patients were starting first line therapy, 25% second line and 16.7% third line. CTC counts (per 7.5cc) ranged from 0 to 1238 (median 2, geometric mean 3.63); none were detected in 29 (30.2%) patients, 1 to 4 in 25 (26%) and 5 or more in 42 (43.8%) patients. CTCs were not associated with age, estrogen receptor, progesterone receptor, HER2, line of treatment, lymph-vascular invasion or tumor grade. Compared to metastatic disease at other sites, CTCs were higher in the presence of bone (p=0.027) and liver metastases (p=0.002) and with progressing bone (p=0.018) and liver (p=0.012) metastases. CTCs were significantly associated with CRP (R =0.25, p=0.014), IL-6 (R=0.31, p=0.002), PAI-1 (R=0.31, p=0.002), Ca15-3 (R=0.44, p=&lt;0.0001) and Ca 125 (R=0.21, p=0.04) but not with VEGF and TNFa (R = 0.11, p= 0.29 and R = 0.16, p=0.11, respectively).

Conclusion: CTCs were associated with bone and liver metastases and with higher levels of inflammatory and tumor markers, potentially reflecting tumor burden. Additional inflammatory marker assays are underway. Future studies are warranted to confirm these findings.

Citation Format: Lohmann AE, Chang M, Dowling RJO, Ennis M, Amir E, Elser C, Brezden-Masley C, Vandenberg T, Lee E, Fazae K, Stambolic V, Goodwin PJ. Association of inflammatory and tumor markers with circulating tumor cells in metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-02-12.