Clinical verification of body mass index and tumor immune response in patients with breast cancer receiving preoperative chemotherapy

Abstract

Purpose: The body mass index (BMI) is commonly used as a simple indicator of obesity; patients with early-stage breast cancer who are obese (OB) per BMI measurements have been shown to have high postoperative recurrence and low survival rates. On the other hand, it has been shown that lymphocytes present in the vicinity of malignant growths that are involved in the tumors' immune responses influence the efficacy chemotherapy. Therefore, we hypothesized that OB patients with breast cancer have a lower density of tumor-infiltrating lymphocytes (TILs), which may influence the therapeutic effect of preoperative chemotherapy (POC). In this study, we measured pretreatment BMI and TILs in patients with breast cancer who underwent POC, examined the correlations between these two factors, and retrospectively analyzed their therapeutic outcomes and prognoses.

Methods: The participants in this study were 421 patients with breast cancer who underwent surgical treatment after POC between February 2007 and January 2019. The patient's height and weight were measured before POC to calculate the BMI (weight [kg] divided by the square of the height [m²]). According to the World Health Organization categorization, patients who weighed under 18.5 kg/m² were classified as underweight (UW), those ≥18.5 kg/m² and > 25 kg/m² were considered normal weight (NW), those ≥25 kg/m² and < 30 kg/m² were overweight (OW), and those ≥30 kg/m² were OB. The TILs were those lymphocytes that infiltrated the tumor stroma according to the definition of the International TILs Working Group 2014.

Results: The median BMI was 21.9 kg/m² (range, 14.3-38.5 kg/m²); most patients (244; 64.5%) were NW. Among all 378 patients with breast cancer, the TIL density was significantly lower in OB than in NW and OW patients (vs. NW: p = 0.001; vs. OW: p = 0.003). Furthermore, when examining patients with each breast cancer type individually, the OS of those with TNBC who had low BMIs was significantly poorer than that of their high-BMI counterparts (log rank p = 0.031).

Conclusions: Our data did not support the hypothesis that obesity affects the tumor immune microenvironment; however, we showed that being UW does affect the tumor immune microenvironment.

Keywords: Body mass index; Breast cancer; Preoperative chemotherapy; Tumor immune microenvironment; Tumor-infiltrating lymphocytes.

Fig. 1

Comparison of tumor-infiltrating lymphocytes (TILs) density by differences in BMI categorized (UW; underweight, NW; normal weight, OW; overweight, OB; obese) by box-plot diagrams. X indicates the average value. All two groups were analyzed by Student’s t-test. Between the two groups not shown is p > 0.1. The p-value between the two groups without the p-value is greater than 0.1. A all case, B hormone receptor positive breast cancer (HRBC), C HER2-enriched breast cancer (HER2BC), D triple-negative breast cancer (TNBC)

Fig. 2

Kaplan-Meier stratification curve based on BMI categorized (UW; underweight, NW; normal weight, OW; overweight, OB; obese) for disease- free survival (DFS). A all case, B hormone receptor positive breast cancer (HRBC), C HER2-enriched breast cancer (HER2BC), D triple-negative breast cancer (TNBC)

Fig. 3

Kaplan-Meier stratification curve based on BMI categorized (UW; underweight, NW; normal weight, OW; overweight, OB; obese) for overall survival (OS). A all case, B hormone receptor positive breast cancer (HRBC), C HER2-enriched breast cancer (HER2BC), D triple-negative breast cancer (TNBC)

Fig. 4

Kaplan-Meier stratification curve based on BMI categorized (UW; underweight, NW; normal weight, OW; overweight, OB; obese) for disease-specific survival (DFS). A all case, B hormone receptor positive breast cancer (HRBC), C HER2-enriched breast cancer (HER2BC), D triple-negative breast cancer (TNBC)