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Bcl2 and Ki67 refine prognostication in luminal breast cancers

Significance statement

Invasive breast cancer is a heterogeneous disease with multiple subtypes that differ in histology and biologic features. Despite the great development in risk stratification, the outcome still varies among patients within the same prognostic group, especially in patients with luminal cancers. Bcl2 and Ki67 have emerged as important prognostic markers, but their use as standard prognostic markers is still controversial. It could partly due to their relatively limited prognostic value when using alone. The varied methodologies for their evaluation may also contribute to their limited usage. Bcl2 has been evaluated for its staining intensity or percentage alone. Our findings demonstrated a greater efficacy when evaluating Ki67 and Bcl2 expression using a combined approach for the prognostication of luminal breast cancers. Using this approach, Ki67low/Bcl2high phenotype predicted the best outcome while  Ki67high/Bcl2low phenotype was the worst.  Importantly, the prognosis of the ‘mixed-bag’ category of grade/stage2 luminal cancers could be further stratified by this combined analysis. Furthermore, this approach, when added with PR expression, could also refine luminal A cancers outcome prediction. These results highlighted the potential clinical value for this combined analysis in the management of breast cancer patients, particularly those with luminal cancers.

Bcl2 and Ki67 refine prognostication in luminal breast cancers. Global Medical Discovery





Journal Reference

Chen LY, Tsang JY, Ni YB, Chan SK, Chan KF, Zhang S, Tse GM. Breast Cancer Res Treat. 2015;149(3):631-43.

Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.


Combined B-cell lymphoma 2 (Bcl2) and Ki67 expression for breast cancer prognostication has been proposed recently. However, the combinatorial  relationship with patient outcome, clinico-pathologic features, and various biomarkers has not been fully explored. Bcl2 and Ki67 expression were examined in a large cohort of breast cancers. Differential  Bcl2 and Ki67 combinatorial analysis, particularly in luminal cancers, were evaluated with respect to the clinico-pathologic features, biomarkers profile and outcome. Combined Bcl2/Ki67 phenotypes classified by Bcl2 and  Ki67 cutoffs showed a better correlation with outcome. Multivariate analysis revealed  this to be an independent prognostic factor in luminal cancers. Both Ki67and Bcl2 contributed to the prognostic implications of different subgroups defined by Bcl2/Ki67 combination phenotypes with clinico-pathologic features and biomarkers profile. Ki67low/Bcl2high cases showed better DFS (HR = 2.17, P = 0.015) and OS (HR = 3.217, P = 0.015) compared to Ki67high/Bcl2low cases. Interestingly, Ki67low/Bcl2 high cases also showed better outcome than other phenotypes in grade 2 cancers (log-rank = 4.844, P = 0.028) and TNM stage 2 cancers (log-rank = 8.161, P = 0.004). This classification by Bcl2/Ki67 combination phenotypes, together with PR expression, can also refine luminal A cancers prognostication. Not all PR low luminal A cases had poorer outcome compared to the PR high luminal A cases; poor prognosis was only limited to those with also low Bcl2 (log-rank = 23.568, P < 0.001 compared to PR high Bcl2 high cases). The combined Ki67/Bcl2 phenotyping was useful in luminal cancers  prognostication. It also refined prognostication in intermediate groups (grade 2 and stage 2 cancers) of luminal cancers; and aided in further classification of luminal A cancers.

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