Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes

Abstract

A B S T R A C T PurposeTo improve on current standards for breast cancer prognosis and prediction of chemotherapy benefit by developing a risk model that incorporates the gene expression-based "intrinsic" subtypes luminal A, luminal B, HER2-enriched, and basal-like. MethodsA 50-gene subtype predictor was developed using microarray and quantitative reverse transcriptase polymerase chain reaction data from 189 prototype samples. Test sets from 761 patients (no systemic therapy) were evaluated for prognosis, and 133 patients were evaluated for prediction of pathologic complete response (pCR) to a taxane and anthracycline regimen. ResultsThe intrinsic subtypes as discrete entities showed prognostic significance (P ϭ 2.26E-12) and remained significant in multivariable analyses that incorporated standard parameters (estrogen receptor status, histologic grade, tumor size, and node status). A prognostic model for nodenegative breast cancer was built using intrinsic subtype and clinical information. The C-index estimate for the combined model (subtype and tumor size) was a significant improvement on either the clinicopathologic model or subtype model alone. The intrinsic subtype model predicted neoadjuvant chemotherapy efficacy with a negative predictive value for pCR of 97%. ConclusionDiagnosis by intrinsic subtype adds significant prognostic and predictive information to standard parameters for patients with breast cancer. The prognostic properties of the continuous risk score will be of value for the management of node-negative breast cancers. The subtypes and risk score can also be used to assess the likelihood of efficacy from neoadjuvant chemotherapy.

Ferroportin and Iron Regulation in Breast Cancer Progression and Prognosis

“…Our results reveal that (i) ferroportin gene expression is a previously unrecognized determinant of outcome that in logistic regression analysis is independent of other prognostic factors; (ii) ferroportin not only equals the best clinical predictors of outcome in breast cancer patients but also tracks with recently identified molecular subtypes of breast cancer that can add significant prognostic and predictive information to standard outcome parameters of breast cancer (47); (iii) the marked decrease in tumor growth in vivo of ferroportin-overexpressing breast cancer cells provides evidence that ferroportin expression not only is a marker of poor prognosis in primary breast cancer but also contributes to a clinically aggressive phenotype; and (iv) the additive value of ferroportin and hepcidin gene expression in separating good- and poor-prognosis patients provides further support for a critical role of iron homeostasis in breast cancer behavior.…”

Basal‐like breast cancer engages tumor‐supportive macrophages via secreted factors induced by extracellular S100A4

“…The data were obtained from TCGA's dbGAP data portal and log2‐transformed prior to analysis. Subtypes were called using PAM50 (Parker et al ., 2009). We also used PAM50s value for evaluation of how correlated a tumor is to the basal‐like subtype.…”

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists

“…Up to 25% of clinically ER þ tumors are classified as of nonluminal subtype by gene expression methods. 11 Similarly, nearly a third of the clinically HER2 þ (FISH and/or IHC) are not classified as belonging to HER2-enriched category. 11 At least for now, treatment decisions are made on the basis of clinical (and not gene expression) assays.…”

“…The gene expression microarraybased class discovery studies pioneered by the Stanford group have led to the identification of at least five molecular breast cancer subtypes: luminal A, luminal B, normal breast-like, HER2, and basallike. [6][7][8][9][10][11] Although based on the analysis of a limited number of samples and with somewhat different definitions for the various molecular groups in these studies, this approach to the classification of breast cancer has captured the attention of oncologists, pathologists, and scientists alike.…”