Plasma human mammaglobin mRNA associated with poor outcome in patients with breast cancer

Abstract

ABSTRACT. Different treatment outcomes and prognoses in patients with breast cancer can be observed with similar clinical predictors; this is because the biology of breast cancer is complex and heterogenous, involving multiple unknown contributing factors. We looked for plasma human mammaglobin (hMAM) mRNA by RT-PCR in 82 Korean patients with breast cancer to determine if there is an association Plasma mammaglobin mRNA and prognostic factors between the presence of plasma hMAM mRNA in these patients and known prognostic factors. The prognostic usefulness of detection of plasma hMAM mRNA expression in these patients was also evaluated by determining overall survival and event-free survival. A significant difference was observed in the rate of positivity of plasma hMAM mRNA between the early stages of cancer (stages I-II, 23.4%) and advanced stages (stages III-IV, 82.9%). The expression rates of estrogen receptor, progesterone receptor, and HER-2/neu in the breast tissue of these patients, by immunohistochemistry, were 69.5, 75.6, and 20.7%, respectively. In the univariate analysis, plasma hMAM expression was significantly correlated with high histological and nuclear grades, nodal metastasis, and negative estrogen receptor and progesterone receptor status. Patients negative for plasma hMAM mRNA had significantly higher rates of event-free survival compared to the patients positive for plasma hMAM mRNA. However, no significant association with overall survival was observed for expression of plasma hMAM mRNA (P = 0.16). Qualitative detection of plasma hMAM mRNA appears to be associated with unfavorable prognostic factors and lower rates of event-free survival in patients with breast cancer.

Relationship between Human Mammaglobin mRNA in Peripheral Blood and Overall Survival in Breast Cancer Patients: A Systematic Review and Meta-Analysis

“…Increased mammaglobin expression in breast cancer was associated with clinical and biologic features characteristic of a less aggressive phenotype as expression was significantly higher in estrogen receptor (ER)-positive tumors [23,24]. A small number of reports has shown that expression of mammaglobin affects disease (or event) free survival (DFS or EFS) and OS, in agreement with numerous studies showing that mammaglobin is one of the most promising markers for breast cancer diagnosis [25][26][27][28][29][30]. However, the relationship between mammaglobin and OS, a gold standard primary end point to evaluate the outcome of any drug, biologic, intervention or procedure that is assessed in oncologic clinical trials [31], is controversial among researchers.…”

“…The percentage of mammaglobin expression in peripheral blood ranged 8.0% to 48.8% in breast cancer patients. Four studies included sample obtained from patients with metastatic breast cancer [25][26][27]29].…”

“…In addition, they did not show EFS data [29]. We judged risk of bias in the assessment of study confounding as moderate because OS data were analyzed by only univariate analysis [25][26][27].…”

“…Of the six publications, four studies analyzed DFS/EFS using univariate and/or multivariate analyses [26][27][28]30]. Univariate analysis showed shorter DFS/EFS in patients with expression of mammaglobin in peripheral blood than in patients without expression of mammaglobin [26,27,30].…”

“…However, the relationship between mammaglobin and OS, a gold standard primary end point to evaluate the outcome of any drug, biologic, intervention or procedure that is assessed in oncologic clinical trials [31], is controversial among researchers. Some reports demonstrate that high expression of mammaglobin in peripheral blood decreases OS of breast cancer patients and some reports find the opposite [25][26][27][28][29][30].…”