Minimal residual disease (MRD) in the bone marrow in ER-α-positive primary breast cancer patients
- 1.6k Downloads
KeywordsBreast Cancer Bone Marrow Primary Breast Cancer Minimal Residual Disease Estrogen Action
We conducted a study to determine whether a group of estrogen-induced genes could be used to detect and monitor for micrometastases in the bone marrow of patients with breast cancer.
We data-mined for potential markers of estrogen action, verified their relationship to ER in cell lines and purified cells from patient biopsies, and checked their estrogen-inducibility after developing a real-time quantitative PCR assay for each. We then examined 99 bone marrow samples obtained over 2 years during the follow up of good (n = 7) or poor (n = 19) prognosis patients to determine the expression frequency.
We discovered that the expression of eight out of 23 genes, identified by data-mining, were estrogen-regulated. We developed real-time quantitative PCR (QPCR) assays for measurement of the genes for which ESTs were available (ER-α, PR and GATA-3, EEIG-1, EP-3, PS2). We examined their expression in purified breast cancer cells from primary cancers and also from metastases from endocrine-resistant cancers and confirmed that these genes were still expressed. Of these, three were expressed in peripheral blood, excluding them as candidate markers. We then examined 79 samples of bone marrow from 19 poor prognosis patients and 20 from seven good prognosis patients. We found that GATA-3 and ER expressions were significantly higher in the bone marrow of poor-prognosis patients.
GATA-3 and ER appear to be potentially useful markers, in addition to CK19, for monitoring the effects of treatment in the bone marrow of patients with ER-positive breast cancer.
This work was funded by the Breast Cancer Research Trust (MTDB) (MS) and Cancer Research (UK) (RCC).