Research article

Comparison of molecular phenotypes of ductal carcinoma in situ and invasive breast cancer

Rulla M Tamimi^1,2 , Heather J Baer^1,2 , Jonathan Marotti³ , Mark Galan³ , Laurie Galaburda³ , Yineng Fu³ , Anne C Deitz⁴ , James L Connolly³ , Stuart J Schnitt³ , Graham A Colditz⁵ and Laura C Collins³

¹  Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA

²  Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA

³  Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02115, USA

⁴  Worldwide Epidemiology, GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA, 19426, USA

⁵  Department of Surgery, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA

author email corresponding author email

Breast Cancer Research 2008, 10:R67doi:10.1186/bcr2128

Published:	5 August 2008

See related letters by Bhargava and Dabbs, http://breast-cancer-research.com/content/10/5/404 and Tamimi et al., http://breast-cancer-research.com/content/10/5/405

Abstract

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 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.

Methods

We 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.

Results

The 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.

Conclusion

The 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.