Bcl-2 is a highly significant prognostic marker of hormone-receptor-positive, human epidermal growth factor receptor-2-negative breast cancer

Seong, Min Ki; Lee, Ju Young; Byeon, Jangmoo; Sohn, Yeun Ju; Seol, Hyesil; Lee, Jin Kyung; Kim, Eun‐Kyu; Kim, Hyun Ah; Noh, Woo Chul

doi:10.1007/s10549-015-3305-7

Cited by 23 publications

(29 citation statements)

References 27 publications

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“…The present study reveals high expression levels of Bcl-2 in the luminal A and luminal B subtypes of breast cancer in comparison with that in the HER2 + and triple-negative molecular subtypes. These results are concordant with those from Seong et al (53), which also described a significant association between Bcl-2-positive tumors, and a younger patient age, early stage, lower grade, positive expression of ER and PR, and negative expression of HER2. Patients with Bcl-2/ER/PR-positive and HER2-negative tumors in this previous study also exhibited an improved prognosis (53).…”

Section: Discussionsupporting

confidence: 92%

“…These results are concordant with those from Seong et al (53), which also described a significant association between Bcl-2-positive tumors, and a younger patient age, early stage, lower grade, positive expression of ER and PR, and negative expression of HER2. Patients with Bcl-2/ER/PR-positive and HER2-negative tumors in this previous study also exhibited an improved prognosis (53). A significant correlation between Bcl-2 expression levels and hormone receptor status demonstrates that Bcl-2 is a potential effective marker of hormonal responsiveness in patients with ER/PR positive breast cancer.…”

Section: Discussionsupporting

confidence: 92%

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Age-associated prognostic and predictive biomarkers in patients with breast cancer

et al. 2017

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To date, no comprehensive prognostic or predictive marker profiling analysis has been performed in association with the age of patients with breast cancer. In the present study, 632 breast cancer tissue samples were analyzed for expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), B-cell lymphoma (Bcl)-2 protein, HER2 gene amplification, proliferation [as evaluated by proliferating cell nuclear antigen (PCNA) and Ki-67 index], tumor grade, histological type and molecular subtype. The data revealed correlations with the age of patients. A statistically significant positive correlation was identified between patient age and expression of ER (P<0.0001). There was no significant association between patient age and PR, HER2 protein expression, HER2 gene amplification or PCNA. A significant negative correlation between age and Ki-67 expression (P<0.0001) as well as grade of tumor (P=0.007) was identified. The spectrum of molecular subtypes differed according to age (P=0.0003). The highest incidence of aggressive triple-negative and HER2-positive breast cancer was present in patients aged between 20 and 39 years. Luminal A subtype was the most frequent cancer subtype in patients from age 40 onwards, where proliferation activity declined with age and expression of hormone receptors increased along with Bcl-2 expression. Aggressive forms of breast cancer were more common in younger patients. Prognostic and predictive markers have a complex age-specific distribution. The findings of less aggressive luminal A and B subtypes in older patients, and the positive correlation with ER, PR and Bcl-2 expression reveal the potential efficacy of Bcl-2 as a marker of hormone responsiveness in these patients.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Age-associated prognostic and predictive biomarkers in patients with breast cancer

et al. 2017

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“…Although they reported that BCL2 was a favorable prognostic factor regardless of ER, PR, and HER2, BCL2 was not analyzed according to the combination of HR(+) and HER2(−). Seong et al [24] reported that BCL2 expression was an independent, favorable prognostic factor only in breast cancer patients with the HR(+)/HER2(−) subtype and that BCL2 was not a significant prognostic factor in the other subtypes, including HR(+)/HER2(+), HR(−)/HER2(+), and HR(−)/HER2(−) subtypes.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Influence of BCL2 on Molecular Subtypes of Breast Cancer

et al. 2017

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PurposeWe aimed to reveal the prognostic influence of B-cell CLL/lymphoma 2 (BCL2) on molecular subtypes of breast cancer.MethodsWe 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.ResultsRegarding 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.ConclusionThe 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.

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“…In addition to demographic and basic clinical information, an increasing number of novel prognostic markers have been explored and identified 10 – 12 . However, the main problem for most of these studies is that biomarkers rely on sophisticated molecular and/or genetic tests 11 , 13 – 16 . The practical application of the novel tests is inevitably restricted by its cost and complexity.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of routine laboratory variables in prediction of breast cancer recurrence

Zhu

et al. 2017

Sci Rep

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The prognostic value of routine laboratory variables in breast cancer has been largely overlooked. Based on laboratory tests commonly performed in clinical practice, we aimed to develop a new model to predict disease free survival (DFS) after surgical removal of primary breast cancer. In a cohort of 1,596 breast cancer patients, we analyzed the associations of 33 laboratory variables with patient DFS. Based on 3 significant laboratory variables (hemoglobin, alkaline phosphatase, and international normalized ratio), together with important demographic and clinical variables, we developed a prognostic model, achieving the area under the curve of 0.79. We categorized patients into 3 risk groups according to the prognostic index developed from the final model. Compared with the patients in the low-risk group, those in the medium- and high-risk group had a significantly increased risk of recurrence with a hazard ratio (HR) of 1.75 (95% confidence interval [CI] 1.30–2.38) and 4.66 (95% CI 3.54–6.14), respectively. The results from the training set were validated in the testing set. Overall, our prognostic model incorporating readily available routine laboratory tests is powerful in identifying breast cancer patients who are at high risk of recurrence. Further study is warranted to validate its clinical application.

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Bcl-2 is a highly significant prognostic marker of hormone-receptor-positive, human epidermal growth factor receptor-2-negative breast cancer

Cited by 23 publications

References 27 publications

Age-associated prognostic and predictive biomarkers in patients with breast cancer

Age-associated prognostic and predictive biomarkers in patients with breast cancer

Prognostic Influence of BCL2 on Molecular Subtypes of Breast Cancer

Prognostic value of routine laboratory variables in prediction of breast cancer recurrence

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