Bcl2 and Ki67 refine prognostication in luminal breast cancers

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 Ki67 and 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/Bcl2high 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.