Verification of the effects of calcium channel blockers on the immune microenvironment of breast cancer

BMC Cancer. 2019 Jun 24;19(1):615. doi: 10.1186/s12885-019-5828-5.

Abstract

Background: A higher density of tumor-infiltrating lymphocytes (TILs) can lead to greater therapeutic effects and improved prognoses in cancer treatment. Similar results have been observed in breast cancer, particularly in triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2-enriched breast cancer. Calcium channel blockers (CCBs) are antihypertensive drugs (AHTs) that have also been reported to suppress the functions of T cells and macrophages. In this study, we evaluated TILs before pre-operative chemotherapy (POC) in breast cancer and retrospectively analyzed the correlation between CCBs and TILs or prognosis.

Methods: Of the patients treated with POC, 338 who had evaluable TILs were enrolled in this study. The correlations among TILs were evaluated according to standard methods, and CCB use and prognosis were investigated retrospectively.

Results: Before POC, 65 patients (19.2%) took AHTs (CCBs: 41/338, 12.1%). The TIL density was significantly lower among patients administered CCBs for the group of all patients and for patients with TNBC (p = 0.040, p = 0.009, respectively). Additionally, patients with TNBC who were administered CCBs showed significantly lower response rates for POC (p = 0.040). In all patients receiving POC, no significant differences in disease-free survival (DFS) or overall survival (OS) were observed in patients administered CCBs (p = 0.712, p = 0.478, log-rank tests, respectively). Furthermore, no significant differences were found, even in patients with TNBC (DFS: p = 0.441, OS: p = 0.727, log-rank tests, respectively).

Conclusions: In patients with TNBC undergoing treatment for hypertension with CCBs, TILs in the needle biopsy specimens before treatment were significantly lower, and the response rate of POC was not sufficient. Thus, the immunosuppressive effects of CCBs may also affect the immune microenvironment.

Keywords: Breast cancer; Calcium channel blockers; Immune microenvironment; Pre-operative chemotherapy; Tumor-infiltrating lymphocytes.

MeSH terms

  • Adult
  • Aged
  • Biopsy, Needle
  • Calcium Channel Blockers / therapeutic use*
  • Cell Count
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Middle Aged
  • Multivariate Analysis
  • Neoadjuvant Therapy
  • Prognosis
  • Retrospective Studies
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Microenvironment / drug effects*
  • Tumor Microenvironment / immunology*
  • Young Adult

Substances

  • Calcium Channel Blockers
  • Immunosuppressive Agents