J Breast Cancer.  2017 Mar;20(1):54-64. 10.4048/jbc.2017.20.1.54.

Prognostic Influence of BCL2 on Molecular Subtypes of Breast Cancer

• Hwang KT
• Han W
• Kim J
• Moon HG
• Oh S
• Song YS
• Kim YA
• Chang MS
• Noh DY

• KMID: 2379399
• DOI: http://doi.org/10.4048/jbc.2017.20.1.54

Abstract

PURPOSE
We aimed to reveal the prognostic influence of B-cell CLL/lymphoma 2 (BCL2) on molecular subtypes of breast cancer.
METHODS
We analyzed 9,468 patients with primary breast cancer. We classified molecular subtypes according to the National Comprehensive Cancer Network (NCCN) and St. Gallen guidelines, mainly on the basis of the expression of hormonal receptor (HR), human epidermal growth factor receptor 2 (HER2), and Ki-67.
RESULTS
Regarding NCCN classification, BCL2 was a strong favorable prognostic factor in the HR(+)/HER2(-) subtype (p<0.001) and a marginally significant favorable prognosticator in the HR(+)/HER2(+) subtype (p=0.046). BCL2 had no prognostic impact on HR(-)/HER2(+) and HR(-)/HER2(-) subtypes. In relation to St. Gallen classification, BCL2 was a strong favorable prognosticator in luminal A and luminal B/HER2(-) subtypes (both p<0.001). BCL2 was a marginally significant prognosticator in the luminal B/HER2(+) subtype (p=0.046), and it was not a significant prognosticator in HER2 or triple negative (TN) subtypes. The prognostic effect of BCL2 was proportional to the stage of breast cancer in HR(+)/HER2(-), HR(+)/HER2(+), and HR(-)/HER2(-) subtypes, but not in HR(-)/HER2(+) subtype. BCL2 was not a prognostic factor in TN breast cancer regardless of epidermal growth factor receptor expression.
CONCLUSION
The prognostic influence of BCL2 was different across molecular subtypes of breast cancer, and it was largely dependent on HR, HER2, Ki-67, and the stage of cancer. BCL2 had a strong favorable prognostic impact only in HR(+)/HER2(-) or luminal A and luminal B/HER2(-) subtypes, particularly in advanced stages. Further investigations are needed to verify the prognostic influence of BCL2 on molecular subtypes of breast cancer and to develop clinical applications for prognostication using BCL2.

Keyword

Bcl-2; Breast neoplasms; Prognosis; Survival analysis; Triple negative breast neoplasms

MeSH Terms

B-Lymphocytes
Breast Neoplasms*
Breast*
Classification
Humans
Phenobarbital
Prognosis
Receptor, Epidermal Growth Factor
Survival Analysis
Triple Negative Breast Neoplasms
Phenobarbital
Receptor, Epidermal Growth Factor

Figure

• 

  Figure 1 Overall survival curves according to the expression of B-cell CLL/lymphoma 2 (BCL2) in each subtype regarding National Comprehensive Cancer Network classification. Survival curves in HR(+)/HER2(−) (A), HR(+)/HER2(+) (B), HR(−)/HER2(+) (C), and HR(−)/HER2(−) (D) subtypes.HR=hormonal receptor; HER2=human epidermal growth factor receptor 2.

• 

  Figure 2 Overall survival curves according to the expression of B-cell CLL/lymphoma 2 (BCL2) in the subgroups regarding the expression of HR, HER2, and Ki-67. Survival curves in HR(−) (A), HR(+) (B), HER2(+) (C), HER2(−) (D), Ki-67 >14% (E), and Ki-67 ≤14% (F) subgroups.HR=hormonal receptor; HER2=human epidermal growth factor receptor 2.

• 

  Figure 3 Overall survival curves according to the expression of B-cell CLL/lymphoma 2 (BCL2) in each stage. Survival curves in stage I (A), stage II (B), stage III (C), and stage unknown (D) subgroups.

• 

  Figure 4 Overall survival curves according to the expression of B-cell CLL/lymphoma 2 (BCL2) in each subtype classified by each stage. Survival curves for HR(+)/HER2(−) in stage I (A), stage II (B), stage III (C), for HR(+)/HER2(+) in stage I (D), stage II (E), stage III (F), for HR(−)/HER2(+) in stage I (G), stage II (H), stage III (I), and for HR(−)/HER2(−) in stage I (J), stage II (K), stage III (L) subgroups.HR=hormonal receptor; HER2=human epidermal growth factor receptor 2.

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