Survival Analysis of Skeletal Related Events in HR+ Breast Cancer Patients Based on Single NucleotidePolymorphism of ERα Gene

Abstract

Purpose/Aims

To investigate the correlation between the occurrence of G and C alleles at rs9340799 and rs2234693 of the ERα gene and the occurrence and development of bone metastasis and skeletal related events (such as bone pain, pathological fracture and osteoporosis) in HR+ breast cancer patients.

Rationale/Background

Endocrine therapy is the mainstay of treatment in HR+ breast cancers, accounting for about 70% of all breast cancers. The current literature identifies the most common metastatic site of HR+ breast cancer as the skeletal system (59.2%). A series of skeletal related events, such as bone pain, osteoporosis, hypercalcemia, and pathological fracture, have a significant impact on the life quality of breast cancer patients.However, there has been little progress in the diagnosis and treatment.ERα gene is related to the risk of breast cancer and advanced metastasis. Our previous studies showed that SNPs of the ERα gene indicated that patients with G and C alleles at rs9340799 and rs2234693 had a high incidence of abnormal bone metabolism. The effect of ERα SNPs on susceptibility to abnormal bone metabolism suggests that different gene subtypes lead to abnormal estrogen receptor function and destroy the balance of the microenvironment in bone. It is simply a natural attraction for tumor cells to induce the colonization of circulating tumor cells in bone tissue.

Methods

All subjects took AIs and came from Longhua Hospital affiliated with Shanghai University of Traditional Chinese Medicine (2016.1-2017.12). Whole blood samples were collected for ERα gene DNA sequence information. Those who simultaneously contained G and C alleles were defined as group A, and those who did not contain G and C alleles or only contained a single site were defined as group B. Survival status, disease progression, and appearance time were recorded for both groups. Finally, 71 patients were followed up. Kaplan-Meier survival curves were drawn for the results and a single factor COX risk regression analysis was performed.

Results

Total follow-up duration was up to 182 months, and median follow-up was 89 months.① The K-M curve with skeletal related events as the primary endpoint was drawn for survival analysis, and the difference was statistically significant by Log-Rank test (P < 0.05). Median survival without skeletal related events in group A was 96.00 ± 12.53 months and 149.00 ± 40.92 months lower than in group B; there was no statistical difference in single factor COX risk assessment (P > 0.05). ② The K-M curve plotted with the occurrence of bone metastasis or disease progression as the primary endpoint showed a statistically significant difference by Log-Rank test (P < 0.05). The mean progression-free survival time in group A was shorter than in group B, 103.73 ± 5.23 months and 153.83 ± 12.65 months, respectively. The single factor COX risk assessment showed a statistically significant difference (P < 0.05).

Implications

Patients with HR+ breast cancer with G and C alleles are more likely to have bone pain, osteoporosis and bone metastases. SNPs of ERα gene may be an independent risk factor for bone metastasis progression in HR+ patients. We propose a prospective study with a larger sample size.