Abstract P5-17-03: How is inflammatory breast cancer (IBC) different? Integration of clinico-pathological features and circulating tumor cells (CTCs)-based biomarkers for disease and prognostic assessment
Authors: Gerratana L , Zhang Q , Wang C , Shah A , Davis AA , Ye Z , Zhang Y , Abu-Khalaf M , Flaum L , Strickland K , Rossi G , Behdad A , Gradishar W , Platanias L , Yang H , Cristofanilli M 
Published: May 2019

Background: Since IBC is rare and burdened by a particularly unfavorable prognosis, biomarkers able to enhance diagnosis and risk assessment are of pivotal importance and a current unmet need. The aim of this study is to integrate standard clinico-pathological features with CTCs-based biomarkers for a more objective and detailed characterization of IBC.

Methods: This study analyzed retrospectively 251 Advanced Breast Cancer (BC) patients (pts) longitudinally characterized for CTCs and CTCs-based biomarkers at Thomas Jefferson University (Philadephia, PA) and Northwestern University (Chicago. IL). CTCs were enumerated through the CellSearch system (Menarini Silicon Biosystems), and characterized for HER2 expression using the CellSearch CXC Kit. Pts were defined as stage IV aggressive based on the previously reported ≥5 CTCs cut-off (Davis et al. 2018). Associations between clinical features, CTC-derived biomarkers and IBC were tested through uni and multivariate logistic regression. Survival was tested though log-rank test.

Results: Within the analyzed cases, 46% were diagnosed with IBC and among them, 38% was stage IV aggressive. CTC clusters (CTC_CL) were detectable in 12.5% of pts and HER2 positive CTCs (HER2_CTC) in 29.5%. Notably, IBC patients (pts) had a significantly lower CTC count with respect to non-IBC (median 2.5 vs 0 respectively for non-IBC and IBC; P=0.019). BC subtype (HER2 positive BC: OR 2.97; Triple negative BC: OR 2.13), liver and bone involvement (liver: OR 0.46; bone involvement: OR 0.31) were the only significant clinico-pathological features associated with IBC at univariate logistic regression. Interestingly, a marginal significance was observed for soft tissue involvement (OR 1.65, 95%CI 0.95 - 2.87, P=0.07). Stage IV aggressive and presence of HER2_CTC at baseline were moreover inversely associated with IBC. The multivariate model confirmed the significant association between IBC and HER2 positive BC subtype (OR 2.64, 95%CI 1.08 - 6.48, P=0.034), absence of bone involvement (OR 0.31, 95%CI 0.14 - 0.68, P=0.003) and absence of HER2_CTC (OR 0.38, 95%CI 0.15 - 0.98, P=0.045). The baseline detection of CTC_CL was a strong predictor of prognosis for OS in IBC pts (median OS (mOS) 7.6 months (mts) vs not reached (NR) respectively for detectable vs non-detectable CTC_CL; P&lt;0.0001), while a trend was observed for HER2_CTC (mOS 9.9 mts vs NR respectively for detectable vs non-detectable HER2_CTC; P&lt;0.082). Pts negative for CTC_CL at baseline had higher odds of developing CTC_CL in later time-points if stage IV aggressive (OR 12.27, 95%CI 2.10 - 71.57, P=0.005). Despite no baseline factors were significantly associated with the onset of HER2_CTC in later time-points, a trend (P=0.05) was observed for patients without lymph node involvement (OR: 5) and with bone involvement (OR: 4.3).

Conclusion: HER2_CTC and in particular CTC_CL are promising prognostic predictors in IBC. Stage IV aggressive IBC pts could benefit from a longitudinal CTCs assessment, being more prone to develop CTC_CL and therefore at higher risk of rapid disease progression. Probably due to the tropism for soft tissue, IBC is characterized by a lower number of HER2_CTC.

Citation Format: Gerratana L, Zhang Q, Wang C, Shah A, Davis AA, Ye Z, Zhang Y, Abu-Khalaf M, Flaum L, Strickland K, Rossi G, Behdad A, Gradishar W, Platanias L, Yang H, Cristofanilli M. How is inflammatory breast cancer (IBC) different? Integration of clinico-pathological features and circulating tumor cells (CTCs)-based biomarkers for disease and prognostic assessment [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 P5-17-03.