Tumor-infiltrating lymphocytes are correlated with response to neoadjuvant chemotherapy in triple-negative breast cancer

Abstract

The purpose of the present study was to identify histological surrogate predictive markers of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC). Among 474 patients who received NAC and subsequent surgical therapy for stage II-III invasive breast carcinoma between 1999 and 2007, 102 (22%) had TNBC, and 92 core needle biopsy (CNB) specimens obtained before NAC were available. As controls, CNB specimens from 42 tumors of the hormone receptor-negative and HER2-positive (HR-/HER2+) subtype and 46 tumors of the hormone receptor-positive and HER2-negative (HR+/HER2-) subtype were also included. Histopathological examination including tumor-infiltrating lymphocytes (TIL) and tumor cell apoptosis, and immunohistochemical studies for basal markers were performed, and the correlation of these data with pathological therapeutic effect was analyzed. The rates of pCR at the primary site were higher for TNBC (32%) and the HR-/HER2+ subtype (21%) than for the HR+/HER2- subtype (7%) (P = 0.006). Expression of basal markers and p53, histological grade 3, high TIL scores, and apoptosis were more frequent in TNBC and the HR-/HER2+ subtype than in the HR+/HER2- subtype (P = 0.002 for TIL and P < 0.001 for others). In TNBC, the pCR rates of tumors showing a high TIL score and of those showing a high apoptosis score were 37 and 47%, respectively, and significantly higher or tended to be higher than those of the tumors showing a low TIL score and of the tumors showing a low apoptosis score (16 and 27%, respectively, P = 0.05 and 0.10). In a total of 180 breast cancers, the pCR rates of the tumors showing a high TIL score (34%) and of those showing a high apoptosis score (35%) were significantly higher than those of the tumors showing a low TIL score (10%) and those of the tumors showing a low apoptosis score (19%) (P = 0.0001 and 0.04, respectively). Histological grade and basal marker expression were not correlated with pCR. Although the whole analysis was exploratory, the degree of TIL correlated with immune response appear to play a substantial role in the response to NAC in TNBC.

Effect of neoadjuvant chemotherapy in patients with triple-negative breast cancer: A meta-analysis

“…A total of 480 studies were first identified for evaluation. Based on the criteria described in the methods, 19 publications were eligible for inclusion in the present meta-analysis (10,12,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). The bibliographies of these 19 publications were also searched, but this did not provide further studies for inclusion.…”

“…A total of 13 stu dies (10,(15)(16)(17)(18)(19)(20)24,25,(27)(28)(29)(30) reported the pCR rates in patients with TNBC and non-TNBC who received NAC. There was no heterogeneity between the results of different studies (I 2 =23%, P=0.21), so the fixed-effects model was applied for data analysis.…”

“…7). In addition, two pooled analyses of p53 (18,26,28) and CK5/6 (12,20,26) levels revealed no association between these molecules and pCR rate (P>0.05; Figs. 8 and 9).…”

Pathologic complete response after neoadjuvant therapy of breast cancer: pitfalls and shortcomings

“…A multitude of markers has been proposed to better predict outcome of neoadjuvant chemotherapy, reports on another 4 of these markers are published in this issue of the journal [10][11][12][13]. Therefore, some general prerequisites should be described for the development and validation of such new markers: preferably markers should be searched for separately in cohorts with either HR?/HER-, HER2?, or triple-negative tumors; new markers should be immediately validated on independent data sets before their release; and markers should not only be correlated with the occurrence of a pCR but also with survival.…”

Using neoadjuvant therapy for breast cancer in clinical practice: when and how?

“…This issue also contains reports of novel predictive markers such as p53 mutation status, the extent tumor infiltrating lymphocyte and the cell death pathway mediator Serpin3 [16][17][18]. However, markers predictive of specific agents and regimens are needed for clinical decisionmaking and will require further evaluation in both neoadjuvant and adjuvant trials.…”