Prognostic significance of the primary tumor site and immune indexes in patients with estrogen receptor-positive, human epidermal growth factor receptor-2-negative breast cancer

Abstract

Background: The ability to predict high risk factors for recurrence after neoadjuvant chemotherapy (NAC) is controversial. The purpose of the present study was to investigate the prognostic significance of tumor location, tumor-infiltrating lymphocyte (TIL) level, and pretreatment lymphocyte-to-monocyte ratio (LMR) in determining the survival of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer after treatment with NAC.

Methods: The clinical data of 285 ER-positive, HER2-negative patients with clinical stage II-III breast cancer were analyzed from January 2009 to January 2015. To explore the prognostic factors for ER-positive, HER2-negative patients, we combined the conventional clinicopathological prognostic factors with tumor location, pretreatment LMR, and TIL. In addition, samples from 79 patients, who did not achieve pathological complete response (pCR) testing after NAC, were selected for hematoxylin-eosin (HE) staining to analyze the effect of TIL on prognosis.

Results: An LMR >5.2 was correlated with better 5-year disease-free survival (DFS) and overall survival (OS; P<0.001 and P<0.001, respectively). Patients with lower-inner/central quadrant tumors had lower 5-year DFS and OS than patients with tumors in the other quadrants (P=0.012 and P=0.048). Patients with a lower TIL level (≤10%) had better 5-year DFS than patients with a higher TIL level (P=0.010). According to the results of the multivariate analyses, tumor location was an independent prognostic factor for 5-year DFS (P=0.021). Pretreatment LMR was associated with both 5-year DFS and OS (P<0.001 and P<0.001, respectively). In the subgroup analysis stratified by TIL level, the TIL level and the initial clinical stage were associated with 5-year DFS (P=0.027 and P<0.001, respectively).

Conclusions: We explored the prognostic significance of the tumor site, TIL level, and pretreatment LMR level for ER-positive, HER2-negative patients. We concluded that the lower-inner/central quadrant tumors, TIL >10%, and pretreatment LMR level ≤5.2 were correlated with a poor prognosis. More aggressive NAC and/or endocrine therapy with internal mammary node radiotherapy (IMN-RT) should be administered to address the relatively poor prognosis of patients with breast carcinoma presenting the aforementioned adverse factors.

Keywords: Breast cancer; estrogen receptor (ER); human epidermal growth factor receptor-2 (HER2); lymphocyte-to-monocyte ratio (LMR); neoadjuvant chemotherapy (NAC); tumor site; tumor-infiltrating lymphocyte (TIL).

Figure 1

Receiver-operator curve and area under the curve (AUC) for lymphocyte-to-monocyte ratio.

Figure 2

Receiver-operator curve and area under the curve (AUC) for tumor-infiltrating lymphocytes.

Figure 3

Survival curves for patients stratified according to lymphocyte-to-monocyte ratio. (A) Five-year disease-free survival (DFS); (B) overall survival (OS).

Figure 4

Survival curves according to tumor location. (A) Five-year disease-free survival (DFS); (B) overall survival (OS).

Figure 5

Survival curves according to tumor-infiltrating lymphocytes (TIL). (A) Five-year disease-free survival (DFS); (B) overall survival (OS).

Figure 6

Representative hematoxylin-eosin staining of the tumor-infiltrating lymphocytes (TIL) of breast cancer patients (200×). (A) TIL expression: 4%; (B) TIL expression: 12%; (C) TIL expression: 20%.