Molecular subtyping for clinically defined breast cancer subgroups

IntroductionBreast cancer is commonly classified into intrinsic molecular subtypes. Standard gene centering is a routinely done prior to molecular subtyping but can produce inaccurate classifications when the distribution of clinicopathological characteristics in the study cohort differs from that of the training cohort which was used to derive the classifier. Methods: We propose a subgroup-specific gene centering method to perform molecular subtyping on a study cohort that has a skewed distribution of clinicopathological characteristics relative to the training cohort. On such a study cohort, we center each gene on a specified percentile, where the percentile is determined from a subgroup of the training cohort with similar clinicopathological characteristics to the study cohort. We demonstrate our method using the PAM50 classifier and its associated University of Northern Carolina (UNC) training cohort. We consider study cohorts with skewed clinicopathological characteristics, including subgroups composed of a single prototypic subtype of the UNC-PAM50 training cohort (n = 139), an external estrogen receptor (ER)-positive cohort (n = 48) and an external triple-negative cohort (n = 77). Results: Compared to standard gene centering, subgroup-specific gene centering substantially improves individual subtype predictions on the corresponding prototypic tumor sets of the PAM50 training cohort with accuracies of 77 to 100% versus 17 to 33%. It reduces classification er...
Source: Breast Cancer Research - Category: Cancer & Oncology Authors: Source Type: research