Comparison of molecular phenotypes of ductal carcinoma in situand invasive breast cancer

Laurie Galaburda,Rulla M Tamimi,Laura C Collins,Stuart J Schnitt,James L Connolly,Heather J Baer,Jonathan Marotti,Graham A Colditz,Mark Galan,Yineng Fu,Anne C Deitz

doi:10.1186/bcr2128

Abstract

IntroductionAt least four major categories of invasive breast cancer that are associated with different clinical outcomes have been identified by gene expression profiling: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) and basal-like. However, the prevalence of these phenotypes among cases of ductal carcinoma in situ (DCIS) has not been previously evaluated in detail. The purpose of this study was to compare the prevalence of these distinct molecular subtypes among cases of DCIS and invasive breast cancer.MethodsWe constructed tissue microarrays (TMAs) from breast cancers that developed in 2897 women enrolled in the Nurses' Health Study (1976 to 1996). TMA slides were immunostained for oestrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR). Using these immunostain results, cases were grouped into molecularly defined subtypes.ResultsThe prevalence of the distinct molecular phenotypes differed significantly between DCIS (n = 272) and invasive breast cancers (n = 2249). The luminal A phenotype was significantly more frequent among invasive cancers (73.4%) than among DCIS lesions (62.5%) (p = 0.0002). In contrast, luminal B and HER2 molecular phenotypes were both more frequent among DCIS (13.2% and 13.6%, respectively) as compared with invasive tumours (5.2% and 5.7%, respectively) (p < 0.0001). The basal-like phenotype was more frequent among the invasive cancers (10.9%) than DCIS (7.7%), although this difference was not statistically significant (p = 0.15). High-grade DCIS and invasive tumours were more likely to be HER2 type and basal-like than low- or intermediate-grade lesions. Among invasive tumours, basal-like and HER2 type tumours were more likely to be more than 2 cm in size, high-grade and have nodal involvement compared with luminal A tumours.ConclusionThe major molecular phenotypes previously identified among invasive breast cancers were also identified among cases of DCIS. However, the prevalence of the luminal A, luminal B and HER2 phenotypes differed significantly between DCIS and invasive breast cancers.

Highlights

At least four major categories of invasive breast cancer that are associated with different clinical outcomes have been identified by gene expression profiling: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) and basallike
The major molecular phenotypes previously identified among invasive breast cancers were identified among cases of ductal carcinoma in situ (DCIS)
The molecularly distinct breast cancer subgroups identified to date include luminal subtypes A and B

Summary

Introduction

At least four major categories of invasive breast cancer that are associated with different clinical outcomes have been identified by gene expression profiling: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) and basallike. The molecularly distinct breast cancer subgroups identified to date include luminal subtypes A and B Antibodies against oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR) have been useful for this purpose This approach to molecular classification (that is, using immunostaining as a surrogate for expression profiling) is arguably the most practical approach to phenotyping large numbers of archived specimens for which fresh tissue is not available for expression array analysis [9,10,11]. Application of this method to archival tissues from existing studies provides the opportunity to correlate tissue-marker data with long-term exposures and follow-up data

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