A study by Paul Pharoah and colleagues published in this week's PLoS Medicine evaluates immunohistochemistry-based subtype classification of breast tumors for the prediction of disease outcome. Their analysis is based on more than 10,000 breast cancer cases with early disease, and examines the influence of a patient's tumour type on the prediction of future survival.
As has been shown previously the three subtypes of ER negative disease have a poorer outcome than the ER positive disease subtypes in the short term. However, this study has shown that in the long term, the ER negative disease subtypes have a better prognosis. This study has also conclusively demonstrated that the so-called triple negative tumours (ER-, PR- and HER2-) can be divided into two sub-types (basal and non-basal) with the basal subtype having a poorer prognosis.
The observed survival patterns were independent of any systemic adjuvant therapy, suggesting that tumour biology and molecular heterogeneity within breast cancer subtypes, rather than the choice of therapy, determined the survival trends. The authors recommend that this prognostic method should be incorporated into clinical practice.
A related Perspective by Stefan Ambs in the same issue examines the clinical significance of this large study and discusses the limitations of subtype classification for prognostication and targeted therapy in the management of breast cancer.
Funding: Funding of the Amsterdam Breast Cancer Study was provided by the Dutch Cancer Society (grants NKI 2001-2423; 2007-3839) and the Dutch National Genomics Initiative. The Helsinki Breast Cancer Study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (110663), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The immunohistochemical analysis of cases from the Jewish General Hospital and Vancouver General Hospital studies was funded by the Canadian Breast Cancer Research Alliance. The Mayo Clinic Breast Cancer Study was funded by US National Institutes of Health grant CA122340 and an NIH Sponsored Program of Research Excellence (SPORE) in Breast Cancer (CA116201). The immunohistochemical analysis of breast cancers from the Melbourne Collaborative Cohort Study was supported by Australian NHMRC grants 209057, 251553 and 5047 11 and infrastructure provided by The Cancer Council Victoria. Polish Breast Cancer Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Sheffield Breast Cancer Study was supported by Yorkshire Cancer Research and the Breast Cancer Campaign. The Study of Epidemiology and Risk factors in Cancer Heredity is funded by a programme grant from Cancer Research UK. The UK NIHR Cambridge Biomedical Research Centre and the Cambridge Experimental Cancer Medicine Centre support the work of EP, S-JD, CC, and PDP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: Research in the Genetic Pathology Evaluation Centre is supported in part by an unrestricted educational grant from Sanofi-Aventis Canada.
Citation: Blows FM, Driver KE, Schmidt MK, Broeks A, van Leeuwen FE, et al. (2010) Subtyping of Breast Cancer by Immunohistochemistry to Investigate a Relationship between Subtype and Short and Long Term Survival: A Collaborative Analysis of Data for 10,159 Cases from 12 Studies. PLoS Med 7(5): e1000279.doi:10.1371/journal.pmed.1000279
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Related PLoS Medicine perspective:
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Citation: Ambs S (2010) Prognostic Significance of Subtype Classification for Short- and Long-Term Survival in Breast Cancer: Survival Time Holds the Key. PLoS Med 7(5): e1000281. doi:10.1371/journal.pmed.1000281
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