Methods for diagnosis, prognosis and treatment of primary and metastatic basal-like breast cancer and other cancer types
Inventors
Ray, Partha S. • Bagaria, Sanjay • Cui, Xiaojiang • Wang, Jinhua
Assignees
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Publication Number
US-9074253-B2
Publication Date
2015-07-07
Expiration Date
Abstract
In one embodiment, a method of theranostic classification of a breast cancer tumor is provided, comprising obtaining a breast cancer tumor sample from a subject, detecting an expression level of FOXC1, comparing the expression level of FOXC1 to a predetermined cutoff level, and classifying the breast cancer tumor sample as belonging to a theranostic basal-like breast cancer tumor subtype or a theranostic hybrid basal-like breast cancer tumor subtype when the expression level of FOXC1 is higher than the predetermined cutoff level. In other embodiments, methods for predicting a prognosis of a basal-like breast cancer and methods of treating a basal-like breast cancer are provided.
Core Innovation
The invention provides a method of theranostic classification of a breast cancer tumor. It determines an expression level of FOXC1 in a breast cancer tumor sample by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), using forward and reverse cDNA primers having the cDNA sequences of SEQ ID NO: 6 and SEQ ID NO: 7, respectively.
After determining FOXC1 expression level, the method classifies the breast cancer tumor sample as a theranostic basal-like breast cancer subtype or a theranostic hybrid basal-like breast cancer tumor subtype. The classification is based on whether the tumor sample is determined to have a high expression level of FOXC1 above a 90th percentile level of FOXC1 expression levels for a dataset of breast cancer tumors comprising all known breast cancer subtypes.
The description further relates FOXC1 to ER/PR/HER2-defined hybrid subtypes and indicates poor prognosis, including brain metastasis and therapy resistance, when FOXC1 is high.
Claims Coverage
The independent claim contains two core inventive decision elements: determining FOXC1 expression in a breast cancer tumor sample by qRT-PCR using specified SEQ ID NO: 6 and SEQ ID NO: 7 cDNA primers, and classifying the tumor sample into theranostic basal-like versus theranostic hybrid basal-like subtypes when FOXC1 expression is above a defined 90th percentile threshold for a dataset containing all known breast cancer subtypes. A dependent claim narrows the tumor sample type to formalin-fixed paraffin embedded (FFPE) specimens.
FOXC1 expression determination by qRT-PCR using specified primers
Determining an expression level of FOXC1 in a breast cancer tumor sample by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), using forward and reverse cDNA primers having the cDNA sequences of SEQ ID NO: 6 and SEQ ID NO: 7, respectively.
Theranostic basal-like or hybrid basal-like classification using a 90th percentile FOXC1 cutoff
Classifying the breast cancer tumor sample as a theranostic basal-like breast cancer subtype or a theranostic hybrid basal-like breast cancer tumor subtype when the breast cancer tumor sample is determined to have a high expression level of FOXC1, wherein the high expression level of FOXC1 is above a 90th percentile level of FOXC1 expression levels for a dataset of breast cancer tumors, the dataset comprising all known breast cancer subtypes.
FFPE tumor sample limitation
Specifying that the breast cancer tumor sample is a formalin-fixed paraffin embedded (FFPE) specimen.
Overall, the claim coverage focuses on a theranostic classification framework driven by FOXC1 expression measured by qRT-PCR with primers SEQ ID NO: 6 and SEQ ID NO: 7, and subtype assignment based on whether FOXC1 is above a 90th percentile cutoff across a dataset covering all known breast cancer subtypes, with a dependent limitation to FFPE samples.
Stated Advantages
Enables theranostic classification of a breast cancer tumor into basal-like versus hybrid basal-like subtypes based on FOXC1 expression level.
Identifies tumors with high FOXC1 expression (above a 90th percentile cutoff) as candidates for a theranostic hybrid basal-like or basal-like subtype classification.
Documented Applications
Theranostic classification of breast cancer tumors for identifying theranostic basal-like breast cancer subtypes or theranostic hybrid basal-like breast cancer tumor subtypes based on FOXC1 expression.
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