Elevated Levels of Serum Tumor Markers CEA and CA15-3 Are Prognostic Parameters for Different Molecular Subtypes of Breast Cancer

<div><p>Background & Aims</p><p>The utility of measuring carcinoembryonic antigen(CEA) and cancer antigen 15-3 (CA15-3) levels in patients with breast cancer remains controversial. The present study aims to investigate the prognostic value of preoperative serum CEA and CA15-3 levels in breast cancer patients.</p><p>Methods</p><p>Serum preoperative CEA and CA 15-3 concentration levels were measured in a total of 432 breast cancer patients. The association of tumor markers levels with clinicopathological parameters and outcomes were analyzed.</p><p>Results</p><p>Elevated serum levels of CEA and CA15-3 were identified in 47 (10.9%) and 60(13.9%) patients, respectively. Larger tumor size, advanced axillary lymph nodal and TNM stage exhibited higher proportion of elevated CEA and CA15-3 levels. The elevation of CEA levels was significantly greater in patients with HER2 positive tumors, and the elevation of CA15-3 levels was significantly greater in ER negative breast patients. Univariate and multivariate Cox’s regression analysis revealed that elevated preoperative CEA and CA 15-3 levels were independent prognostic factors for DFS and OS. When considering the combination of both markers levels, patients with both elevated markers presented the worst survival. Independent prognostic significance of elevated preoperative serum CEA and CA15-3 levels were reconfirmed in Luminal B breast cancer.</p><p>Conclusions</p><p>Preoperative serum levels of CEA and CA15-3 are independent prognostic parameters for breast cancer.</p></div

Kaplan-Meier survival curves of Luminal B breast patients with normal or elevated CEA and CA15-3 levels.

<p>DFS according to CEA(A) and CA15-3(B), OS according to CEA(C) and CA15-3(D).</p

Multivariate Cox’s regression analysis according to tumor size,nodal status, stage, HER2 status, and serum tumor markers.

<p>TNM tumor-node-metastasis, HER2 human epidermal growth factor receptor 2, CA 15–3 cancer antigen 15–3, CEA carcinoembryonic angigen, DFS disease-free survival; OS overall survival, HR, Hazard ratio, CI, Confidence interval.</p><p>*P < 0.05 indicates a significant difference.</p><p>Multivariate Cox’s regression analysis according to tumor size,nodal status, stage, HER2 status, and serum tumor markers.</p

Univariate analysis of prognostic factors for survival time of breast cancer patients.

<p>TNM tumor-node-metastasis, ER estrogen receptor, PR progesterone receptor, HER2 human epidermal growth factor receptor 2, CA 15–3 cancer antigen 15–3, CEA carcinoembryonic angigen, TNBC triple-negative breast cancer, DFS disease-free survival, OS overall survival.</p><p>*P < 0.05 indicates a significant difference.</p><p>Univariate analysis of prognostic factors for survival time of breast cancer patients.</p

Clinicopathological characteristic of subjects and correlation between serum CA 15–3 and CEA level and clinicopathological factors.

<p>TNM tumor-node-metastasis, ER estrogen receptor, PR progesterone receptor, HER2 human epidermal growth factor receptor 2, CA 15–3 cancer antigen 15–3, CEA carcinoembryonic angigen, TNBC triple-negative breast cancer.</p><p>*P < 0.05 indicates a significant difference.</p><p>Clinicopathological characteristic of subjects and correlation between serum CA 15–3 and CEA level and clinicopathological factors.</p

Kaplan-Meier survival curves of patients with normal or elevated CEA and CA15-3 levels.

<p>Disease-free survival (DFS) according to carcinoembryonic antigen (CEA) (A) and cancer antigen 15–3 (CA15-3) (B). Overall survival (OS) according to CEA(D) and CA15-3(E). DFS according to the combination of both marker levels(C) and OS according to the combination of both marker levels (F).</p