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Identification of molecular subtypes within a formalin-fixed, paraffin-embedded breast cancer tumour cohort
Breast Cancer Research volume 12, Article number: P33 (2010)
Breast cancer is not a single disease but is highly heterogeneous at both the molecular and clinical levels. Gene expression profiling of breast tumours by multiple independent groups and technologies have revealed five major molecular subtypes of breast cancer. These molecular differences result in distinct clinical outcomes and responses to treatment.
The gene expression profiling studies that have defined the molecular subgroups of breast cancer to date were performed using fresh frozen tissue. Routine clinical practice dictates the preservation of surgical specimens via paraffin embedding of formalin-fixed tissue. Therefore, derivation of molecular subgroups of breast cancer from formalin-fixed, paraffin-embedded (FFPE) preserved tissue would have more application in the clinical setting as such profiles could be applied to routinely collected specimens.
The Almac Diagnostics' Breast Cancer DSA™ has been optimised for analysis of FFPE samples enabling the use of these valuable archived tissue banks. We have demonstrated the ability to identify the molecular subgroups previously defined within a cohort of sporadic, BRCA1 mutant and BRCA2 mutant FFPE breast tumours as well as defining two novel subgroups within this tumour set. This study demonstrates that it is possible to derive biologically meaningful data from a cohort of archived FFPE tumour samples using the Almac Breast DSA™. We demonstrate that there is considerable molecular diversity within BRCA mutant and sporadic breast tumours, suggesting that traditional assumptions of the behaviour of tumours based on their immunohistochemistry status may not always be correct. At present, a number of clinical trials are stratifying patients for poly(ADP-ribose) polymerase 1 (PARP-1) inhibitor therapy based on BRCA mutation and triple-negative status. The data presented here would suggest that not all BRCA1 mutant, BRCA2 mutant and indeed triple-negative patients are similar at the molecular level and as such will not respond equally to PARP-1 inhibitor or indeed other therapeutics in the same manner.
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Mulligan, J., McDyer, F., Deharo, S. et al. Identification of molecular subtypes within a formalin-fixed, paraffin-embedded breast cancer tumour cohort. Breast Cancer Res 12, P33 (2010). https://doi.org/10.1186/bcr2530
- Breast Cancer
- Breast Tumour
- BRCA1 Mutant
- Molecular Subtype
- FFPE Sample