The Prognostic Value of the Proliferation Marker Phosphohistone H3 (PPH3) in Luminal, Basal-Like and Triple Negative Phenotype Invasive Lymph Node-Negative Breast Cancer

Ivar Skaland,Jan P A Baak,Einar Gudlaugsson,Emiel A M Janssen,Lydia Hui Ru Guo

doi:10.1155/2009/676721

Abstract

Purpose: Prognostic comparison of phosphohistone-H3 (PPH3) with Cytokeratin 5/6 and/or 14 positive (= basal-CK), triple (ER, PR, HER2)-negative (= TNP) and basal-like (= TNP and basal-CK positive) phenotype in invasive breast cancers.Patients and Methods: Classical variables, PPH3, ER, PR, basal-CK and HER2 in 240 T1–2N0M0 patients under 71 years.Results: TNP and basal-like cancers had higher PPH3 expression than the other cancers (mean 48 versus 11, P < 0.001). Fifteen percent of the patients in the whole group, but 32–38% of TNP and basal-like cancers recurred.With multivariate analysis, PPH3 < 13 (n = 156) versus ≥ 13 (n = 84 = 35% of all cases) was the strongest and only prognosticator (10-year survival 96% and 64%, P ≤ 0.001, Hazard ratio = 9.0).Conclusion: PPH3 is the strongest prognosticators in luminal, Triple negative and basal-like T1–2N0M0 invasive breast cancers.

Highlights

Breast cancer is a heterogeneous disease, encompassing a number of distinct biological entities
Invasive lymph node negative breast carcinomas are treated according to tumor size, grade, lymph and blood vessel invasion, age, HER2 and/or hormone receptor status
Cancers are classified as Luminal when ER and or PR is expressed with or without expression of HER2, as triple negative when ER, PR, and HER2 are all negative, as basal-like (= BLC) when TNP and basal cytokeratin (= basal-CK) and/or EGFR is expressed, and as HER2 positive when ER and PR are negative and HER2 is overexpressed

Summary

Introduction

Breast cancer is a heterogeneous disease, encompassing a number of distinct biological entities. Recent gene expression studies have shown that breast cancers can be classified into five main groups with prognostic and predictive value; Luminal A and B, Normal breast-like, HER2 positive, and basal-like [20,29,30,31]. Cancers are classified as Luminal when ER and or PR is expressed with or without expression of HER2, as triple negative (triple negative profile = TNP) when ER, PR, and HER2 are all negative, as basal-like (= BLC) when TNP and basal cytokeratin (= basal-CK) and/or EGFR is expressed, and as HER2 positive when ER and PR are negative and HER2 is overexpressed. The normal-like breast cancers do not express basal cytokeratins, EGFR or HER2 but a TNP without expression of these markers is not necessarily a normal-like tumor as classified by gene expression arrays [1,8,19,23]

Methods

Results

Conclusion