Compositions and Methods for Diagnosis and Treatment of Breast Cancer
The present invention is a population of breast cancer cells with preference for establishing dormancy in bone marrow. The breast cancer cells have characteristics of stem cells and express high levels of Oct4, designated Oct4 hi , but are also not dependent on stem cell gene status. The Oct4 hi cells exhibit functional gap junction intercellular communication with bone marrow stroma, indicating that these cells can establish dormancy and remain resistant to chemotherapy. Also provided by the present invention are a biomarker for metastatic breast cancer, a method for diagnosis and prognosis of breast cancer, and a method for identifying treatments that target dormant metastatic cells.
1 : A breast cancer biomarker comprising a breast cancer cell with a phenotype Oct4 hi /CD44 hi/med /CD24 −/+ .
2 : The biomarker of claim 1 wherein said breast cancer cell establishes gap junctional intercellular communication with bone marrow stroma.
3 : A method for developing a breast cancer prognosis comprising detecting the presence of the biomarker of claim 1 in a patient sample wherein the presence of said biomarker is indicative of a the presence of dormant metastatic breast cancer cells in the patient and a poor prognosis for the patient.
4 : A method for diagnosing metastatic breast cancer comprising detecting the presence of the biomarker of claim 1 in a patient sample, wherein the presence of the biomarker of claim 1 indicates that the patient has metastatic breast cancer.
5 : A method for identifying chemotherapeutic agents that can kill dormant metastatic breast cancer cells in bone marrow comprising:
a) contacting a breast cancer cell with a phenotype Oct4 hi /CD44 hi/med /CD24 −/+ in vitro with an agent; and
b) determining whether the agent is capable of killing said breast cancer cell, wherein death of said breast cancer cell is indicative of the ability of the agent to kill dormant metastatic breast cancer cells in bone marrow.