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. 2013 Oct 1;109(7):1886-94.
doi: 10.1038/bjc.2013.528. Epub 2013 Sep 5.

Identification of key clinical phenotypes of breast cancer using a reduced panel of protein biomarkers

A R Green  1 , D G Powe, E A Rakha, D Soria, C Lemetre, C C Nolan, F F T Barros, R D Macmillan, J M Garibaldi, G R Ball, I O Ellis
Affiliations

Identification of key clinical phenotypes of breast cancer using a reduced panel of protein biomarkers

A R Green et al. Br J Cancer. .

Abstract

Background: Breast cancer is a heterogeneous disease characterised by complex molecular alterations underlying the varied behaviour and response to therapy. However, translation of cancer genetic profiling for use in routine clinical practice remains elusive or prohibitively expensive. As an alternative, immunohistochemical analysis applied to routinely processed tissue samples could be used to identify distinct biological classes of breast cancer.

Methods: In this study, 1073 archival breast tumours previously assessed for 25 key breast cancer biomarkers using immunohistochemistry and classified using clustering algorithms were further refined using naïve Bayes classification performance. Criteria for class membership were defined using the expression of a reduced panel of 10 proteins able to identify key molecular classes. We examined the association between these breast cancer classes with clinicopathological factors and patient outcome.

Results: We confirm patient classification similar to established genotypic biological classes of breast cancer in addition to novel sub-divisions of luminal and basal tumours. Correlations between classes and clinicopathological parameters were in line with expectations and showed highly significant association with patient outcome. Furthermore, our novel biological class stratification provides additional prognostic information to the Nottingham Prognostic Index.

Conclusion: This study confirms that distinct molecular phenotypes of breast cancer can be identified using robust and routinely available techniques and both the luminal and basal breast cancer phenotypes are heterogeneous and contain distinct subgroups.

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Figures

Figure 1
Figure 1
Biplots of classes projected on the first and second principal component axes: (A) for all patients and (B) for only patients assigned to a class.
Figure 2
Figure 2
Breast cancer biological classes. (A) Classification and proportions of cases. (B) Representative immunohistochemical profiles of the biological classes of breast cancer.
Figure 3
Figure 3
Breast cancer biological classes in relation to (A) 5-, (B) 20-year breast cancer-specific survival and (C) 5-, (D) 20-year disease-free survival.
Figure 4
Figure 4
Boxplots of NPI by biological class.
See this image and copyright information in PMC

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