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. 2010 Jan;119(2):379-90.
doi: 10.1007/s10549-009-0575-y.

"V体育官网入口" Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer

Matthew J Ellis  1 , Li Lin, Robert Crowder, Yu Tao, Jeremy Hoog, Jacqueline Snider, Sherri Davies, Katherine DeSchryver, Dean B Evans, Jutta Steinseifer, Raj Bandaru, WeiHua Liu, Humphrey Gardner, Vladimir Semiglazov, Mark Watson, Kelly Hunt, John Olson, José Baselga
Affiliations

Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer

Matthew J Ellis et al. Breast Cancer Res Treat. 2010 Jan.

Abstract

Mutations in the alpha catalytic subunit of phosphoinositol-3-kinase (PIK3CA) occur in approximately 30% of ER positive breast cancers. We therefore sought to determine the impact of PIK3CA mutation on response to neoadjuvant endocrine therapy. Exons 9 (helical domain) and 20 (kinase domain-KD) mutations in PIK3CA were determined samples from four neoadjuvant endocrine therapy trials VSports手机版. Interactions with clinical, pathological, and biomarker response parameters were examined. A weak negative interaction between PIK3CA mutation status and clinical response to neoadjuvant endocrine treatment was detected(N = 235 P < or = 0. 05), but not with treatment-induced changes in Ki67-based proliferation index (N = 418). Despite these findings, PIK3CA KD mutation was a favorable prognostic factor for relapse-free survival (RFS log-rank P = 0. 02) in the P024 trial (N = 153). The favorable prognostic effect was maintained in a multivariable analysis(N = 125) that included the preoperative endocrine prognostic index, an approach to predicting RFS based on post neoadjuvant endocrine therapy pathological stage, ER, and Ki67 levels (HR for no PIK3CA KD mutation, 14, CI 1. 9-105 P = 0. 01). PIK3CA mutation status did not strongly interact with neoadjuvant endocrine therapy responsiveness in estrogen receptor-positive breast cancer. Nonetheless, as with other recent studies, a favorable interaction between PIK3CA KD mutation and prognosis was detected. The mechanism for the favorable prognostic impact of PIK3CA mutation status therefore remains unexplained. .

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Figures

Figure 1A, B, C
Figure 1A, B, C
Remark diagrams for the P024 trial (A), the RAD2222 trial (B) and POL (C) indicating the distribution of specimens in the various analyses reported in the paper.
Figure 1A, B, C
Figure 1A, B, C
Remark diagrams for the P024 trial (A), the RAD2222 trial (B) and POL (C) indicating the distribution of specimens in the various analyses reported in the paper.
Figure 1A, B, C
Figure 1A, B, C
Remark diagrams for the P024 trial (A), the RAD2222 trial (B) and POL (C) indicating the distribution of specimens in the various analyses reported in the paper.
Figure 2A and 2B
Figure 2A and 2B
A. The effect of BEZ235 on pAKT levels in Jurkat cells prepared as either as a lysate and estimated by immunoblotting, or as a cell block and estimated by the semi-quantitative immunohistochemical technique used for the breast tumor analysis. B. A comparison of pAKT levels according to PIK3CA mutation status in samples from the letrozole alone arm of the RAD2222 trial. The Kruskal-Wallis test was used to compare the difference of cytoplasmic pAKT histology score amongst the three groups degrees of freedom (DF)=2 P=0.0453. The Mann-Whitley test was applied to compare PIK3CA wt group to PIK3CA mutant group when KD and HD mutation groups are combined DF=1, P=0.0135.
Figure 3A–E
Figure 3A–E
Interactions between PIK3CA mutations status and RFS in the P024 trial in subgroups defined by the PEPI score (15). Panel A: PIK3CA KD mutation positive cases versus other cases P=0.025 (log rank test). In Panel B–D: effect of PIK3CA status examined within the context of PEPI group 1 (B), group 2 (C) and group 3 (D). In PEPI group 3, the favorable effect of PIK3CA mutation status was significant P=0.007. Panel E: Cox proportional Hazards model that contains the four components of the PEPI model with the addition of PIK3CA KD mutation status.
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References

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    1. Saal LH, Holm K, Maurer M, et al. PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res. 2005;65(7):2554–9. - PubMed
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