J Breast Cancer.  2016 Sep;19(3):252-260. 10.4048/jbc.2016.19.3.252.

BCL2 as a Subtype-Specific Prognostic Marker for Breast Cancer

• Eom YH
• Kim HS
• Lee A
• Song BJ
• Chae BJ

• KMID: 2413949
• DOI: http://doi.org/10.4048/jbc.2016.19.3.252

Abstract

PURPOSE
B-cell lymphoma 2 (BCL2) is an antiapoptosis protein and an important clinical breast cancer prognostic marker. As the role of BCL2 is dependent on the estrogen receptor (ER) status, this effect might differ according to molecular subtypes. The aim of this study was to evaluate the relationship between the prognostic outcomes and BCL2 expression among the molecular subtypes.
METHODS
We retrieved the data of 1,356 patients who were newly diagnosed with malignant breast cancer between November 2006 and November 2011. Immunohistochemistry was used to measure ER, progesterone receptor, human epidermal growth factor receptor 2 (HER2), Ki-67, and BCL2 expression. We classified breast cancer into five molecular subtypes based on the 13th St. Gallen International Expert Consensus, including luminal A, luminal B (HER2-negative), luminal B (HER2-positive), HER2-overexpression, and triple-negative subtypes. We analyzed the clinicopathological features and assessed the correlation between BCL2 expression and clinical outcomes, such as relapse-free survival (RFS) and disease-specific survival (DSS) according to the five molecular subtypes.
RESULTS
A total of 605 cases of breast cancer (53.8%) showed BCL2 expression. BCL2-positive expression was associated with young age (<50 years, p=0.036), lower histological grade (p<0.001), low Ki-67 level (<14%, p<0.001), hormone receptor positivity (p<0.001), HER2 negativity (p<0.001), luminal breast cancer (p<0.001), and low recurrence rate (p=0.016). BCL2-positive expression was also associated with favorable 5-year RFS (p=0.008, 91.4%) and DSS (p=0.036, 95.6%) in all the patients. BCL2-positive expression in luminal A breast cancer resulted in significantly favorable 5-year RFS and DSS (p=0.023 and p=0.041, respectively). However, BCL2 expression was not associated with the prognosis in the other subtypes.
CONCLUSION
The prognostic role of BCL2 expression in breast cancer is subtype-specific. BCL2 expression differs according to the molecular subtype and is a good prognostic marker for only luminal A breast cancer.

Keyword

B-cell lymphoma 2 protein; Breast neoplasms; Prognosis; Tumor biomarkers

MeSH Terms

Biomarkers, Tumor
Breast Neoplasms*
Breast*
Consensus
Estrogens
Humans
Immunohistochemistry
Lymphoma, B-Cell
Phenobarbital
Prognosis
Receptor, Epidermal Growth Factor
Receptors, Progesterone
Recurrence
Weights and Measures
Biomarkers, Tumor
Estrogens
Phenobarbital
Receptor, Epidermal Growth Factor
Receptors, Progesterone

Figure

• 

  Figure 1 Flowchart of the patient cohort included in this study. Exclusion criteria was noninvasive carcinoma (e.g., ductal carcinoma in situ), distant metastasis at diagnosis, and any other malignancy. Different frequency of BCL2 positive expression was observed depending on the molecular subtypes. BCL2=B-cell lymphoma 2; HER2=human epidermal growth factor receptor 2; TNBC=triple-negative breast cancer.

• 

  Figure 2 Kaplan-Meier analysis of 5-year relapse-free survival (RFS) and disease-specific survival (DSS) for B-cell lymphoma 2 (BCL2) positive and BCL2-negative patients. Patients expressing BCL2 have longer 5-year RFS (A) (p=0.008) and 5-year DSS (B) (p=0.036) compared to patients with no BCL2 expression.

• 

  Figure 3 Kaplan-Meier analysis of 5-year relapse-free survival (RFS) and 5-year disease-specific survival (DSS) for B-cell Lymphoma 2 (BCL2)-positive and BCL2-negative luminal A breast cancer patients. Patients expressing BCL2 have longer 5-year RFS (A) (p=0.023) and 5-year DSS (B) (p=0.041).

• 

  Figure 4 Kaplan-Meier analysis of 5-year relapse-free survival (RFS) and 5-year disease-specific survival (DSS) for B-cell lymphoma 2 (BCL2)-positive and BCL2-negative breast cancer patients. BCL2-positive luminal B, human epidermal growth factor receptor 2 (HER2) overexpression, and triple-negative breast cancer (TNBC) breast cancer patients have no longer 5-year RFS (A, C, E, and G) and 5-year DSS (B, D, F, and H) compared to patients with no BCL2 expression.

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