Getting deep in the luminal B breast cancer subtype and its ki67 cut-off value

Introduction

Inside the luminal breast cancer (BC) group, the B subclass carries a worse prognosis and is less responsive to hormonal treatment. Identification of the luminal B group, by Sørlie and colleagues [1], has been less consistent than other subclasses; and gene signatures based in estrogen-related genes or proliferation are better to identify this BC subclass. Cheang and colleagues genetically evaluated 144 luminal ER-positive HER2-negative tumors by IHC; they found a ki67 cutoff value of 13.25% to differentiate B from A subclasses [2]. No differentiation for PR status was done. The luminal B subgroup is usually defined as ki67 >13 if ER-positive, as well as HER2-positive or PR-negative. The target of this abstract is to evaluate behavior of different luminal B subsets.

Methods

We reviewed early BC cases evaluated at Hospital 12 de Octubre between 1995 and 2007 and selected 710 initially operated luminal B BC. We divided this group into four subsets as shown in Table 1 and analyzed their clinical-pathologic features and outcomes. Additionally, we evaluated the prognostic behavior of lowering the ki67 cutoff in the ER⁺PR⁺HER2^- group (820 patients).

Table 1

Results

The median ki67 value for the ER⁺PR^- group was 17%. A ki67 cutoff at 14% discerns two groups of different prognosis inside the luminal group (extracting HER2⁺ and PR^-); and comparison of ki67 cutoff between 14 and 11% found overlapped CI (median: 6.31 (5.99 to 6.62) vs. 6.49 (6.21 to 6.78)). Table 1 summarizes different characteristics and prognosis based on molecular features (statistical comparisons exclude the ER^-PR⁺ subgroup).

Conclusion

Subsets inside the luminal B subtype according to expression of HER2, ER, PgR and ki67 have different features and behaviors. In the ER⁺PR⁺HER2^- subgroup, ki67 cutoff should be re-evaluated in order to avoid misclassification and subsequent under-treatment of poorer prognosis tumors as luminal A hormono-sensitive phenotype.