Prognostic and Predictive Value of Tumor-Infiltrating Lymphocytes in a Phase III Randomized Adjuvant Breast Cancer Trial in Node-Positive Breast Cancer Comparing the Addition of Docetaxel to Doxorubicin With Doxorubicin-Based Chemotherapy: BIG 02-98

Abstract

In node-positive, ER-negative/HER2-negative BC, increasing lymphocytic infiltration was associated with excellent prognosis. Further validation of the clinical utility of tumor-infiltrating lymphocytes in this context is warranted. Our data also support the evaluation of immunotherapeutic approaches in selected BC subtypes.

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

“…109 In the Breast International Group 2-98 trial, retrospective-prospective analyses detected a positive correlation between the number of TILs and survival in TNBC. 110 The presence of TILs is also associated with increased pathological complete response (pCR) rates. The first randomized controlled trial indicated that a relationship exists between increased numbers of TILs and pCR rates.…”

Basal‐like breast cancer engages tumor‐supportive macrophages via secreted factors induced by extracellular S100A4

“…TME can influence both cancer progression and therapeutic responses (McMillin et al ., 2013; Quail and Joyce, 2013), and tumor‐related inflammation is now recognized as a hallmark of cancer (Hanahan and Weinberg, 2011). The tumor's immunological portrait – the presence of tumor‐infiltrating leukocytes, their nature, and the profile of regulatory cytokines – is determinative for BC outcome and therapeutic response (Fridman et al ., 2012; Loi et al ., 2013). Good outcome/response is associated with a high fraction of cytotoxic T cells and assisting T‐helper 1 cells, whereas poor outcome/resistance is linked to the dominance of T‐helper 2 cells and tumor‐associated macrophages (TAMs) (Savas et al ., 2016).…”

Predictive and Prognostic Role of Tumor-Infiltrating Lymphocytes for Early Breast Cancer According to Disease Subtypes: Sensitivity Analysis of Randomized Trials in Adjuvant and Neoadjuvant Setting

“…1) [16-18, 21-23, 33, 34]. Of these, 4 RCTs (1,694 patients) [21][22][23]33] were conducted in the neoadjuvant setting and 4 RCTs (3,820 patients) [16][17][18]34] were conducted in the adjuvant setting. Selected arms of neoadjuvant trials and their characteristics are listed in Table 1.…”

“…Three RCTs (2,132 patients) [17,18,34] included an arm with luminal disease subtype, 3 RCTs (618 patients) [17,18,34] included an arm with HER2-positive disease, and 4 RCTs (1,070 patients) [16][17][18]34] included an arm with TNBC.…”

“…In this regard, large series of data suggest that tumors with higher TIL counts are associated with good prognosis in contrast with those with lower TILs [13][14][15]. However, in single studies, the prognostic effect was mostly robust in triple-negative BC (TNBC) and less well-established in other subtypes [16][17][18][19].…”