Biomedical Engineering Reference
In-Depth Information
lying diseases or the physiological (and psychological) state of the patient. It is
readily observed that breast cancer appears/behaves differently in premenopausal
versus postmenopausal women. Is this the same disease in a developmentally differ-
ent host or does it reflect different diseases beyond estrogen receptor (ER) and
progestrone receptor (PR) status? Also, statistical evidence relates risk for breast
cancer to smoking, alcohol use, and body weight factors.
Are these risks uniform throughout a patient's lifetime? Not likely! For exam-
ple, the breast undergoes developmental changes continuously during the
in utero
to postmenopause transition (Figure 1.2), and the mechanistic basis for risk is
probably related to differences in gene expression, protein expression, protein modi-
fication, and so forth that will accompany these developmental changes. Biomedi-
cal informatics approaches this problem by analyzing the clinical data
epidemiologically to determine what level of exposure at what age may be most crit-
ical for establishing risk from one or more of these factors and then combining this
with molecular characterization of the underlying physiological changes (Figure
1.3). In this manner, more than a simple correlation between these risk factors and
breast disease can be realized because the molecular processes, including
upregulation and downregulation of the gene/protein pathway, can be identified;
these are potentially mechanistically related to observed risk. This enhances the like-
lihood for identifying new diagnostics as well as therapeutics and perhaps, more
importantly, establishing a more highly refined basis for making lifestyle and envi-
ronmental choices for the patient and the physician.
The complexity of the underlying biological relationship between patient and
disease has not been adequately addressed by translational research, systems biol-
ogy, or personalized medicine to date and requires refocusing their potential to
describe these underlying processes. A fundamental aspect of this complexity is the
fact that disease, although frequently described in terms of “disease state,” actually
represents a process that evolves over time, through a integrative relationship
involving the patient's genetics and his interaction with lifestyle and environmental
factors, always starting significantly before any symptoms may appear.
Genetic risk
+
Lifestyle/environment/exposure [
F
(
t
)]
Disease
Breast Development
Cumulative development
Lactation
Menopause
Menarch
Peri-
menopause
Child-bearing
Fetal stages
Figure 1.2
Major stages of breast development in a woman's lifetime.
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