Five-year survival in luminal breast cancer patients: relation with intratumoral activity of proteasomes

Abstract

Background: The purpose of the study was to analyze the relationship between the caspase-like (CL) and chymotrypsin-like (ChTL) activities of proteasomes and the 5-year overall and metastasis-free survival rates in patients with luminal breast cancer.

Methods: The study included 117 patients with primary operable invasive breast cancer (T_1-2N_0-1M₀). Tissue samples from breast cancer patients were obtained as a result of the radical mastectomy or breast conserving surgery, which was a first line of therapy. The ChTL and CL proteasomes activities in the tumor tissue and in the surrounding adjacent breast tissues were assessed using the fluorometric method. The coefficients of ChTL (cChTL) and CL (cCL) proteasomes activities were also determined. The coefficients were calculated as the ratio of the corresponding proteasomes activity in the tumor tissue to the surrounding adjacent breast tissues. Within 5 years of follow-up, hematogenous metastases occurred in 14% of patients with luminal A breast cancer, in 31% of patients with luminal B human epidermal growth factor receptor-2 (HER-2) negative and in 23% of patients with luminal B HER-2 positive breast cancers. The study protocol was approved by the Local Ethics Committee of the Cancer Research Institute of Tomsk National Research Medical Center. Written informed consent was obtained from all patients.

Results: An increase in the ChTL and CL proteasomes activities was shown in all studied molecular subtypes of breast cancer compared to adjacent tissues. It was found that the cChTL of >35.9 U/mg protein and the cCL of >2.21 in breast cancer patients were associated with the development of distant metastases. In patients with luminal A breast cancer, the 5-year metastasis-free survival rates were associated only with the value of cCL of proteasomes (log-rank test: P=0.008). In patients with luminal B HER-2 negative breast cancer, the 5-year metastasis-free survival rates were associated with the levels of ChTL and cCL proteasomes activities (log-rank test: P=0.02 and P=0.04, respectively).

Conclusions: The data obtained on the correlation of 5-year metastasis-free survival rates with the level of proteasomes activities indicate the possibility of their use as additional prognostic criteria for breast cancer.

Keywords: Luminal breast cancer; hematogenous metastases; long-term outcome; prognosis; proteasomes activity.

Figure 1

Kaplan-Meier curves of metastasis-free survival depending on (A) the value of ChTL proteasomes activity in the tumor and (B) the cCL proteasomes activity in luminal breast cancer patients. ChTL, chymotrypsin-like; cCL, coefficient of caspase-like.

Figure 2

Kaplan-Meier curves of overall survival (A) and metastasis-free survival (B) of breast cancer patients in different molecular subtypes. Disease progression (development of hematogenous metastases) at 5 years of follow-up occurred in 31% patients with luminal B HER-2 negative breast cancer; in 23% of patients with luminal B HER-2 positive breast cancer and in 16% of patients with luminal A breast cancer. BC, breast cancer; HER-2, human epidermal growth factor receptor-2.

Figure 3

Kaplan-Meier curves of metastasis-free survival depending on the cCL proteasomes activity in patients with luminal A breast cancer. cCL, coefficient of caspase-like.

Figure 4

Kaplan-Meier curves of metastasis-free survival depending on (A) the values of ChTL proteasomes activity and (B) depending on the level of the cCL proteasomes activity in patients with luminal B HER-2 negative breast cancer. ChTL, chymotrypsin-like; cCL, coefficient of caspase-like; HER-2, human epidermal growth factor receptor-2.