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Genomic Instability and Prognosis in Breast Carcinomas

¹ Division of Cellular and Molecular Analysis, Department of Oncology and Pathology; ² Department of Medical Epidemiology and Biostatistics; and ³ Radiumhemmet, Department of Oncology and Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden

Requests for reprints: Yudi Pawitan, Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Box 281, 17176 Stockholm, Sweden. Phone: 46-8-5248-3983; Fax: 46-8-314-975. E-mail: yudi.pawitan{at}ki.se

Background: We recently reported that DNA content of breast adenocarcinomas, cytometrically assessed by diploid (D), tetraploid (T), and aneuploid (A) categories, can be further divided into genomically stable and unstable subtypes by means of the stemline scatter index (SSI). The aim of the present study was to survey the clinical correlates and the prognostic value of the SSI in a consecutive series of 890 breast cancer patients.

Results: Genomically stable subtype had a significantly better survival compared with the unstable subtype within each ploidy category: D (P = 0.04), T (P = 0.008), and A (P = 0.004). By contrast, no statistically significant difference in survival was observed between the D, T, and A categories within the stable (P = 0.23) and unstable subtypes (P = 0.12). Among A tumors, the unstable subtype tended to be larger, more frequently estrogen- and progesterone-receptor negative, and to be of higher grade compared with the stable subtype. Stable D tumors tended to have lower grade than the unstable subtype, but among the D and T tumors, genomic instability was not associated with receptor status. Within the Elston grade 3, lymph node–positive or estrogen receptor–positive subgroups, patients with stable tumors had significantly better survival compared with unstable tumors (P = 0.01, 0.002, and 7.2E–5, respectively).

Conclusions: The SSI contributes supplementary biological and clinical information in addition to ploidy information alone. Objective classification of breast adenocarcinomas into stable and unstable subtypes is a useful prognostic indicator independent of established clinical factors. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1630–5)