Abstract P2-08-59: Different predictive and prognostic impact of intra-tumor heterogeneity, tumor biology, and microenvironment in triple negative breast cancer
Authors: Hayashi N , Nakamura M , Kobayashi D , Suzuki K , Yamauchi H 
Published: May 2019

Abstract
Background
Intra-tumor heterogeneity, tumor biology, and microenvironment in triple negative breast cancer (TNBC) has been reported to be predictive and prognostic factors. However, it is not well known how these factors are correlated each other according to response to chemotherapy and their prognosis. The aim of this study was to assess the predictive and prognostic impact of these factors in TNBC.
Method
Biopsy samples before neoadjuvant chemotherapy (NAC) from 59 TNBC patients who underwent surgery after NAC from 2001 to 2007 were retrospectively assessed. For tumor biology, tumors were classified as Hormonal related luminal androgen receptor (LAR) if &gt;10% staining of AR, Basal-like if positive for cytokeratin 5/6 and EGFR, and Others. Claudin 1 and p16 expression levels were assessed for intra-tumor heterogeneity. and stromal tumor-infiltrating lymphocytes (Str-Tils) levels for tumor-microenvironment were also assessed as low for ≤10%, Intermediate for 10-49%, and high for &gt;50%.The predictive and prognostic impact of clinicopathological factors including age, nuclear grade (NG), lymph node status, were also assessed. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method and were compared between groups using the log-rank test.
Results
A median overall survival period of the 59 patients was 98 month(6 -172 month).Eighteen (30.5%) were classified in LAR, 16 (27.1%) in Basal-like, and 25 (42.4%) in Others. According to response to NAC, 10 patients (16.9%) achieved pathologic complete response (pCR). These biological classifications were not associated with pCR rate (p=0.135). high-p16 had significantly high pCR rate (p=0.046).However, Str-Tils level was not associated with pCR rate. Patients with lymph node metastasis had significantly low pCR rate (p=0.017).In terms of their prognosis, age&lt;50 had significantly shorter OS and DFS than that of age&gt;50 (OS: p=0.023, DFS: p=0.027). NG3 had a trend of short OS compared to NG 1 or 2 (NG 1 vs 3, OS: p=0.053, and NG 2 vs 3, OS: p=0.073). There were no difference of their prognosis among three tumor biology classifications except Basal-like had significantly shorter OS than that of LAR (LAR vs Basal OS:p=0.041, DFS:p=0.574, LAR vs Others OS:p=0.407, DFS:p=0.866, Basal vs Others OS:p=0.162, DFS:p=0.713).Claudin 1 and p16 expression levels were not associated with OS and DFS. Low-Str-Tils had a trend of shorter OS and DFS than that of intermediate- or high-Str-Tils (low vs int; OS:p=0.085, DFS:p=0.026, low vs high; OS:p=0.062, DFS:p=0.055).In multivariate analysis, age&lt;50 was only independent prognostic factor (p&lt;0.05).
Conclusion
We showed that intra-tumor heterogeneity, tumor biology, and microenvironment had different predictive and prognostic impact in TNBC. These results might suggest the strategy of additional targeting treatment to non-pCR patients.
Citation Format: Hayashi N, Nakamura M, Kobayashi D, Suzuki K, Yamauchi H. Different predictive and prognostic impact of intra-tumor heterogeneity, tumor biology, and microenvironment in triple negative breast cancer [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 P2-08-59.