311Prognostic Gene Biomarkers of Breast Cancer Three genes, homeobox 13
(HOXB13), interleukin-17B receptor (IL17BR) and CHDH, and the
HOXB13:IL17BR ratio index in particular, strongly predict clinical outcome in
breast cancer patients receiving tamoxifen monotherapy. HOXB13:IL17BR index is
a strong independent prognostic factor for ER+ node-negative patients irrespective
of tamoxifen therapy. These two biomarkers serve are the foundation of the
AviaraDx Breast Cancer Profi ling Technology.
Activity of a gene, Dachshund (DACH1), which normally regulates eye develop-
ment and development of other tissues, commandeers cancer-causing genes and
returns them to normal. DACH1 inhibits the expression of the cyclin D1 gene, an
oncogene that is overexpressed in about half of all breast cancers. DACH1 corre-
lates with tumor size, stage and metastasis, and its expression is markedly reduced
in metastatic breast cancer cells, but increased nuclear DACH1 expression predicts
improved patient survival. DACH1 gene reverses the cancerous phenotype, thus
turning the cell back to a premalignant state, and it could be used as a prognostic
biomarker for breast cancer. Other genes that determine cell fate- are being exam-
ined in an attempt to identify new therapeutics for breast cancer and metastasis.
The gene CEACAM6 (carcinoembryonic antigen-related cell adhesion molecule
6) is involved in the spread of breast cancer that has developed resistance to long-
term estrogen deprivation. It may prove to be a useful biomarker for predicting,
which patients have the greatest risk of breast cancer recurrence, so their physicians
can offer the most appropriate treatment plan. The research focused on breast can-
cer cells that had grown resistant to aromatase inhibitors (AIs), anti-hormone drugs
to shut down the enzyme aromatase, which lets the body produce estrogen outside
the ovaries. These drugs represent one of the most effective forms of hormone ther-
apy for postmenopausal women whose breast cancer tests positive for ERs, which
means that estrogen in the body fuels the growth of cancer cells. Unfortunately, one
of the drawbacks to extended use of an AI may be that some of the cancer cells
develop resistance to the drug and are able to grow and spread independent of estro-
gen. Several AI-resistant breast cancer cell lines have been developed in the labora-
tory and found to be very invasive compared to AI-sensitive breast cancer cells.
Analyses of gene activity in these AI-resistant cells shows that they express high
levels of genes associated with invasiveness and metastasis. However, this aggres-
sive behavior could be reversed by using siRNAs to knock out the CEACAM6 gene.
This gene might not only be an important biomarker for metastasis but a possible
target for novel therapies for patients with metastatic breast cancer.
ER-negative basal breast cancer is a heterogeneous disease with at least four
main subtypes. Heterogeneity in the clinical outcome of ER- breast cancer is related
to the variability in expression levels of complement and immune response pathway
genes independently of lymphocytic infi ltration (Teschendorff et al. 2007 ).
Multi-gene Expression Prognostic Constellation (Celera) The prognostic con-
stellation provides information that is distinct from that predicted by routine clini-
cal assessment tools, such as tumor grade, and can quantify risk for metastasis for
variable time periods rather than only categorically for 5 or 10 years. A previously
Personalized Management of Cancers of Various Organs