Abstract P1-07-14: Rates of immune infiltration in patients with triple-negative breast cancers by molecular subtype and in patients with inflammatory and non-inflammatory breast cancers
Authors: Harano K , Wang Y , Lim B , Seitz RS , Morris SW , Bailey DB , Hout DR , Skelton RL , Ring BZ , Masuda H , Rao AUK , Woodward WA , Reuben JM , Ueno NT 
Published: March 2017

Abstract
Background
In patients with triple-negative breast cancer (TNBC), tumor-infiltrating lymphocytes (TILs) have been reported to be associated with improved survival. Lehmann et al. identified 6 molecular subtypes of TNBC [basal-like (BL) 1, BL2, mesenchymal (M), mesenchymal stem like (MSL), immunomodulatory (IM), and luminal androgen receptor (LAR)], and we previously reported that TNBC subtype is a predictor of pathologic complete response (pCR). Recently, the IM gene expression signature has been shown to be indicative of the presence of TILs and has been incorporated into TNBC subtyping as a modifier of the other groups rather than a separate subtype. However, the association between TNBC subtype and the presence of TILs is not known. We hypothesized that the BL2 and LAR subtypes, which have low pCR rates, have low rates of immune infiltration. Inflammatory breast cancer (IBC) is an aggressive cancer that is frequently triple-negative. The association between IBC and the presence of TILs also is not known. In this study, we analyzed the association between TNBC molecular subtype and the IM signature and determined whether the IM signature differed between patients with IBC and non-IBC.
Methods
We retrospectively analyzed 88 patients with TNBC from the World IBC Consortium dataset for whom IBC status was known (IBC, n=39; non-IBC, n=49) and tumor gene expression data were available. TNBC specimens were classified using the TNBCtype algorithm (Insight Genetics, Inc., TN, USA), which uses a 101-gene signature. For each tumor, the TNBCtype algorithm reports the TNBC molecular subtype (BL1, BL2, M, MSL, or LAR) and the IM status, which is described as positive (IM+) or negative (IM-). Recently, Fisher's exact test was used to analyze differences in subtype distribution between the IM+ and IM- tumors.
Results
The subtype distribution differed significantly between the IM+ and IM- tumors
IM signature in TNBC subtypesSubtypeTotal (n=88)IM+ (n=32)IM- (n=56)BL13015 (50)15 (50)BL2202 (100)M808 (100)MSL3113 (42)18 (58)LAR121 (8)11 (92)Not determined53 (60)2 (40) (p=0.0087). The majority of IM+ cases occurred in the BL1 and MSL subtypes. No IM+ cases were observed in the BL2 or M subtypes, and only 1 was observed in the LAR subtype. IM+ cases occurred at roughly the same frequency in patients with IBC (33%) and non-IBC (37%, p=0.73).
Conclusions
TNBC molecular subtypes differ in their degree of immune infiltration, and most IM+ TNBCs are of the BL1 and MSL subtypes. Our finding that the proportion of IM+ cases was not different between IBC and non-IBC indicates that TILs are recruited to the tumor microenvironment similarly in IBC and non-IBC tumors. Further, Pietenpol et al recently showed that the MSL signature represents normal stromal cells rather than tumor cells by performing laser-capture microdissection of TNBC specimen. Validation studies are needed to corroborate and further expand upon our findings.
Citation Format: Harano K, Wang Y, Lim B, Seitz RS, Morris SW, Bailey DB, Hout DR, Skelton RL, Ring BZ, Masuda H, Rao AUK, Woodward WA, Reuben JM, Ueno NT. Rates of immune infiltration in patients with triple-negative breast cancers by molecular subtype and in patients with inflammatory and non-inflammatory breast cancers [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 P1-07-14.