Abstract PD06-04: St. Gallen 2011 clinicopathological subtyping of breast cancer: impact of different proliferation assessment methods

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Abstract Rationale: The St Gallen Consensus 2011 strongly recommends subtyping of breast cancer (BC). However, because there is no data from phase III trials to substanciate adjuvant therapy benefit gene expression arrays were not generally accepted to guide systemic therapy decisions. Instead, the consensus introduced clinicopathological BC subtypes (cpBCST) defined as sets of risk and predictive biomarkers which are established worlwide (Table 1). To discriminate Luminal A vs. Her2 negative Luminal B BCs the St Gallen Consensus recommends Ki67 for defining proliferation. Although, because no standardized methodology or cut-off definition for Ki67 is available so far ‘some alternative measure of proliferation’ was suggested. We analyzed the influence of different proliferation assessment methods on BC subtype distribution. Methods: cpBCST assessment including proliferation measurement by different variants of Ki67-Labeling-Index (KI67LI) was performed on 225 BCs. For comparison we used the Mitotic Activity Index (MAI) as the only prospectively evaluated and best reproducible proliferation measurement (Baak et al 2008). The Ki67-LI was based on counting any nuclear staining of distinctly defined target areas: (1) 100 tumor cells within the hot spot (Ki67-100), (2) 1020 tumor cells in 3 HPF in the tumor periphery including the hot spot (Ki67-1020periphery), and (3) 1020 tumor cells in 3 HPF including hot spot, cold spot, and an intermediate area (Ki67-1020spectrum). Staining quality and counting accuracy was tested as excellent by the 2011 circulation of the German Quality Initiative in Pathology. According to St Gallen, a cut-off <14% was used. The MAI was measured in 10 HPFs with a total area of 1.59 mm2 using a cut-off ≥10 as evaluated by Baak et al. 2008. Results: Conclusions: The delimination of Luminal A and Luminal B Her2 negative BCs according to the St. Gallen Consensus 2011 is highly influenced by the method of proliferation assessment. Using the recommended cut-off <14% all estimations of Ki67LI came out with Luminal A/Luminal B ratios (10–34% vs. 45–69%) which are much lower than those published (44–53% vs. 9–29%). As a consequence, this could lead to more cytotoxic treatment. Therefore, the biological relevance of KI67LI seems to be not unequivocal. Unlike this, proliferation measurement by MAI resulting in a Luminal A/Luminal B ratio of 52% vs. 29% seems more reliable. The differences may be due to the fact that mitotic figures reflect only the M phase, whereas Ki67 stains cells in nearly all phases of the cell cycle. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD06-04.