Rates of immune cell infiltration in patients with triple-negative breast cancer by molecular subtype

Kenichi Harano (1, 2) , Ying Wang (1) , Bora Lim (1) , Robert S. Seitz (3) , Stephan W. Morris (3) , Daniel B. Bailey (3) , David R. Hout (3) , Rachel L. Skelton (3) , Brian Z. Ring (3, 4) , Hiroko Masuda (5) , Arvind U. K. Rao (1) , Steven van Laere (6) , Francois Bertucci (7, 8) , Wendy A. Woodward (1) , James M. Reuben (1) , Savitri Krishnamurthy (1) , Naoto T. Ueno (9, 1)

1 The University of Texas M.D. Anderson Cancer Center [Houston]
2 Nippon Medical School
3 Insight Genetics
4 HUST - Huazhong University of Science and Technology [Wuhan]
5 Showa University
6 UA - University of Antwerp
7 Département d’Oncologie Médicale [IPC, Marseille]
8 CRCM - Centre de Recherche en Cancérologie de Marseille
9 Department of Breast Medical Oncology [Houston]

In patients with triple-negative breast cancer (TNBC), tumor-infiltrating lymphocytes (TILs) are associated with improved survival. Lehmann et al. identified 4 molecular subtypes of TNBC [basal-like (BL) 1, BL2, mesenchymal (M), and luminal androgen receptor (LAR)], and an immunomodulatory (IM) gene expression signature indicates the presence of TILs and modifies these subtypes. The association between TNBC subtype and TILs is not known. Also, the association between inflammatory breast cancer (IBC) and the presence of TILs is not known. Therefore, we studied the IM subtype distribution among different TNBC subtypes. We retrospectively analyzed patients with TNBC from the World IBC Consortium dataset. The molecular subtype and the IM signature [positive (IM+) or negative (IM-)] were analyzed. Fisher's exact test was used to analyze the distribution of positivity for the IM signature according to the TNBC molecular subtype and IBC status. There were 88 patients with TNBC in the dataset, and among them 39 patients (44%) had IBC and 49 (56%) had non-IBC. The frequency of IM+ cases differed by TNBC subtype (p = 0.001). The frequency of IM+ cases by subtype was as follows: BL1, 48% (14/29); BL2, 30% (3/10); LAR, 18% (3/17); and M, 0% (0/21) (in 11 patients, the subtype could not be determined). The frequency of IM+ cases did not differ between patients with IBC and non-IBC (23% and 33%, respectively; p = 0.35). In conclusion, the IM signature representing the underlying molecular correlate of TILs in the tumor may differ by TNBC subtype but not by IBC status.

Keywords: Gene expression; Breast cancer; Cancer chemotherapy; Inflammation; Immune cells; Androgens; Consortia; Immune receptors

Domains: Life Sciences [q-bio]

Kenichi Harano, Ying Wang, Bora Lim, Robert S. Seitz, Stephan W. Morris, et al.. Rates of immune cell infiltration in patients with triple-negative breast cancer by molecular subtype. PLoS ONE, 2018, 13 (10), pp.e0204513. ⟨10.1371/journal.pone.0204513⟩. ⟨hal-02143557⟩