Prognostic significance of apoptosis and cell proliferation in breast cancer

Introduction

Breast cancer development is the result of an impaired balance between cell proliferation and programmed cell death. While proliferative factors are often considered in the assessment of biological aggressiveness, apoptosis is often overlooked. The aim of this study is to assess the impact of apoptosis on survival and on the risk of relapse in breast cancer.

Methods

Retrospective cohort analysis of operated breast cancer patients in the north of Sweden from January 1st, 1998, to December 29th 2001. Data about TNM stage, S-phase fraction, Ki-67, TILs, PD-L1 expression were collected, and the number of apoptotic cells was assessed using a TUNEL assay and classified as high or low based on the median value.

Results

Baseline tumor characteristics were broadly comparable between groups, with differences mainly observed in the distribution of TILS, HER2 status, and tumor subtype. High TUNEL expression was significantly associated with HER2 positivity (P = 0.019), grade 3 tumors (P = 0.013), and an elevated S-phase fraction (P = 0.002). High-TUNEL tumors displayed slightly higher proportions of high TILS and HER2-positive disease whereas triple-negative tumors were more common in the low-TUNEL group. Overall, the two TUNEL groupsdemonstrated similar tumor biology at baseline.

Breast cancer–specific death occurred more frequently in the high-TUNEL group, although the difference did not reach statistical significance (P = 0.056).

Discussion

High TUNEL levels were associated with negative prognostic markers such as high proliferation rate, grade 3 tumors, and lymph node metastasis. Overall, TUNEL covaried with several key tumor characteristics, indicating that apoptosis assessment may add prognostic value beyond traditional markers.