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Breast cancer continues to be a major concern. Epidemiological cancer data
for the United States continue to show an increase in the number of breast
cancers every year. In spite of this increase, the mortality for breast cancer
is beginning to decline due to early detection and treatment advances.
Even though progress is being made, it is slow. Our basic approaches to
breast cancer diagnosis, detection, and treatment have not changed for decades.
In fact this is true for not only breast cancer but for the majority of other
diseases. With this in mind, it is important to appreciate that we are now on
the verge of major breakthroughs. These breakthroughs are the result of research
in molecular and genetic science, that until now, have been laboratory based.
These breakthroughs are now being applied to clinical medicine. Not only will
there be advances in the very near future, but these advances will be so
profound that this is without a doubt constitute a paradigm shift. This shift is
consistent with Thomas Kuhn's original definition of paradigm as "an
achievement sufficiently unprecedented to attract an enduring group of adherents
away from competing modes of scientific activity and sufficiently open-ended to
leave all sorts of problems for the redefined groups of practitioners to
resolve. " (IN: The Structure of Scientific Revolutions, 1962)
Past and present
To appreciate these changes, it is important to understand our past
and present practices for making a breast cancer diagnosis, determining
prognosis or outcome of breast cancer, and establishing a treatment plan.
Diagnosis of many diseases, including breast cancer, is based on our
obtaining a tissue sample and studying it under the microscope. This is called
"histologic analysis" and involves thinly sectioning the tissue,
placing the section on a glass slide, staining it, and looking at it under the
microscope. The appearance of the tissue under the microscope allows for a
categorization of the tissue as either normal or abnormal, and one of the
abnormal categories is that of cancer
The term prognosis refers to our attempt to predict the outcome of various
diseases, that is, whether an individual will or will not do well given their
illness. It follows that breast cancer prognosis means how an individual with
breast cancer will do, that is, whether she will recur or die from her disease.
The information we use to determine breast cancer prognosis is primarily
information that is obtained from pathology analysis of the cancer tissue.
Pathologists report on the appearance of the cancer cells (differentiation),
measure the diameter of the cancer (size), and examine axillary lymph nodes to
determine whether the cancer is present in the nodes. Taken together, these
factors constitute what is termed the TNM staging system for breast cancer.
Women with a small tumor that has not spread to lymph nodes have a stage I
breast cancer and on average are more likely to have a favorable outlook
compared to women whose tumor is larger or has spread to lymph nodes under the
arm, i.e., stage II or III. The problem with this system for determining
prognosis is that, at best, it is only a guess. There are individuals with early
stage breast cancer who will recur and die from their breast cancer, and
conversely there are other individuals, who have larger cancers or cancers that
have already spread to lymph nodes and who survive for years without any
evidence of recurrence. The problem is that using our present methods of
determining prognosis, we cannot differentiate between these individuals. In
short, we cannot really determine for an individual woman how her breast cancer
will behave and whether she will or will not eventually recur.
Treatment recommendations are based upon our best-guess estimates of an
individual breast cancer patient's prognosis. Women are treated by lumpectomy or
mastectomy and may receive chemotherapy or tamoxifen not based on our ability to
predict how their specific cancer will behave, but rather on our best-guess
determination of how they might do. In essence, we treat not only breast cancer
but most diseases without any ability to tailor therapy to the specific
individual.
Present and future
The entire approach to breast cancer as described above is about to
change. This change is based upon what can be clearly termed the genetic
revolution. Over the past decade there has been extensive research into genes
and how genes regulate cell growth and behavior. Why is gene research so
important, so fundamental, to our understanding and regulating of diseases?
Simply put, genes are the molecular packets that make us what we are and who we
are. Genes make up chromosomes and chromosomes are the molecular structures that
are passed from generation to generation. Genes are composed of molecules called
DNA, and DNA controls the synthesis of specific molecules called proteins.
Proteins are the building blocks of our cells and tissues. Alterations, both
inherited and acquired, in the structure of our DNA result in abnormal
production of proteins, and it is these alterations that can ultimately lead to
the development of a cancer cell. Cancer cells are characterized by their
uncontrolled growth and tendency to spread to distant sites (metastasize).
Through advances in genetic research we are now beginning to understand some
of the key alterations that lead to abnormal growth and development of cells.
With a very recent technological innovation termed microarray analysis, it is
now possible to study thousands of genes and proteins at once and to compare
differences in genetic and protein make-up between different individuals and
different breast cancers.
Early results of this type of research in breast cancer have been startling.
Using these new approaches, we will soon be able to zero-in on the most
fundamental differences that drive one type of breast cancer to eventually
spread and another to lie dormant. Very soon we will be able to obtain a small
sample of the breast cancer from an individual, determine how it will behave,
and select the best therapy. Taking this approach to the next level, we will be
able to figure out the specific biochemical or molecular reactions that are
abnormal and that allow a particular person's cancer to grow and spread, and we
will be able to develop treatments that will be much less radical and much less
toxic than those we use today.
All of this may seem futuristic. It is not. At the Cleveland Clinic, we have
developed a fast-track program dedicated to the translation of these the most
recent and novel genetic and molecular research findings into clinical reality
for breast cancer management. As a key part of this program, individual breast
cancers are studied to determine different genetic and molecular markers which
will eventually lead to new schemes for predicting breast cancer outcomes for
individual patients, not just groups of patients. This research will provide the
basis for developing therapies targeted to specific breast cancers.
Breast cancer diagnosis, prognosis, and treatment are about to change
forever. Clearly these changes will directly impact and directly benefit each
individual who has a newly diagnosed cancer. These advances will undoubtedly
lead very soon to the previously elusive cure for breast cancer.
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