Biomedical Engineering Reference
In-Depth Information
1
2
Although
breast cancer mortality rates have declined in the United States due
to screening and wider use of more effectives systemic adjuvant
therapies,
2008,
including about 40,000 deaths in the United States.
3
a higher proportion of women are receiving adjuvant
therapy who might have been cured without it and are thus being
overtreated. Diagnostic tools that could identify which patients
derived greatest benefit from specific therapies are needed.
13.2
Genomics
Genomics is defined as the study of all of the nucleotide sequences in
an organism. “Genomic profiling” in breast cancer and other cancers
has focused on the evaluation of gene expression, or the translation
of the information encoded in genomic DNA into an RNA transcript.
Although RNA transcripts include messenger RNAs which are
translated into proteins and various other RNAs (e.g., transfer RNA,
ribosomal RNA, micro RNA, and noncoding RNA) that have important
biologic functions, most studies of gene expression profiling in breast
cancer have focused on mRNA expression. The same principles
may be applied to the study of the epigenome,
4,5
6
microRNAs,
or integrative approaches that evaluate combinations of
profiling methods.
proteins,
7
8
In addition, high-throughput massively parallel
sequencing is now feasible, allowing direct sequencing of cDNAs
which may provide not only absolute gene expression levels, but also
information on alternatively spliced isoforms, mutations and novel
transcripts arising from fusion genes.
13.3
Development and Validation of
Multiparameter Assays
The promise and pitfalls in developing multiparameter assays has
been reviewed elsewhere,
9-12
specific criteria have been proposed
for the level of evidence required to define and support their
clinical utility.
13
There are several steps in the development of a
marker, which may broadly classified as (1) conceptualization, (2)
clinical development, (3) technical development, (4) validation,
and (5) application. Development of an accurate assay is largely
a function of the interplay between sample size and classification
difficulty.
14
Criteria
have
been
developed
for
assessing
and
