Despite an abundance of methods to estimate prognosis, the ability to predict a cancer's behavior to tell a patient that they will be cured if they receive treatments X, Y, and Z is still an inexact science. This brings us to the fifth and final factor that determines prognosis. It has no official name, but I call it the biological essence of the cancer. It is truly the key to a cancer's behavior, even though we cannot measure it at this time. The biological essence comes from deep inside the cancer cell to dictate how heartily it grows, how well it resists apoptosis, and how invasively it spreads throughout the body. All of the properties we have discussed thus far are mere surrogates for this biological essence; they all try to approximate it but fail to truly capture it.
For example, how could it have been predicted that a fifty-year-old woman with an early-stage lung cancer (stage I) would ultimately die from lung cancer that returned more aggressively? And how could it have been predicted that a forty-two-year-old man with colon cancer that had spread to the liver and lungs (stage IV) could be cancer free five years after chemotherapy, when the average survival of such patients is under two years? Neither cancer type, stage, health of the patient, nor prognostic factors could have predicted these outcomes. These cases highlight the reality that there is much that science cannot explain about the behavior of cancer.
In scientific circles one often hears the phrase Biology is destiny." This statement means that it is the innate biological properties, or biological essence, of a cancer that most strongly determines how it will behave in the body. For example, why is pancreatic cancer so difficult to treat? Its biological essence leads it to metastasize early and respond poorly to today's cancer therapies. Why is testicular cancer so often cured? Its biological essence makes it melt away with chemotherapy or radiation. When a cancer patient lives much longer than could have been anticipated, the main reason is thought to be the favorable biological essence of that cancer: it grows slower or succumbs to treatment more easily than other cancers of its class.
I have talked to enough people about cancer to learn that many know someone who defied the odds and overcame an incurable" cancer. Certainly, in my oncology practice, I am continually amazed at how some people survive for many years with a cancer that has a dismal prognosis; the treatments worked incredibly well. But beyond the treatments, do I think that some people have a special gift, have found a cure from a healer, or have prayed harder than those who succumbed to cancer? No. I have had the immensely humbling privilege of caring for some of the most courageous, health-conscious, and devout people that anyone could ever meet; many of these individuals faced an insurmountable enemy in a cancer that just could not be beaten down. And whereas some individuals try to do all that they can to fight cancer, there are those who do not want to change their lives any more than they have to. These individuals accept the prescribed therapies but continue their life as uninterrupted as possible. This is also an important coping mechanism that must be respected.
The reality is that the biology of a cancer plays the largest role in determining why some people are cured and some are not. A person's physician and the treatments administered are clearly important; new and better cancer therapies are changing cancer's destiny in many situations. Other factors that may help a person survive include stopping smoking, eating a healthful diet, getting adequate rest and exercise, lowering stress, accepting love and emotional support, and having the will to live. But these cannot overcome an aggressive cancer for which modern medicine has no answer.
By acknowledging the reality that the molecules inside the cancer cell largely determine a cancer patient's prognosis, I do not mean to minimize the tremendous powers of the human mind, heart, and spirit. On the contrary, I would not have been compelled to write this article if I did not believe that these uniquely human traits play a vital role in the healing of the human body. Yet the cancer's biological destiny will largely determine the course it will take. Since we cannot predict this destiny for any cancer, any discussion of prognosis must be accompanied by the caveat that every person and every cancer is unique and that this uniqueness is poorly understood today.
Our ability to provide a highly accurate prognosis to a newly diagnosed cancer patient will depend on advances in science that are able to capture the biological essence of a cancer. Incredibly, these advances are happening today, and we stand at the crossroads of a new era in the field of cancer medicine. Within the next ten years, the diagnosis, estimation of prognosis, and treatments used to battle cancer will all be much more precise than they are today.
Every person's fingerprint is unique. And so is every person's cancer fingerprint. This cancer fingerprint" or cancer signature" consists of all the genes a cancer is using and can be viewed as a computerized readout. Researchers are studying cancer fingerprints intensively for their ability to predict the behavior of a cancer. This field of study is called genomics because all the genes in a cell are collectively known as the genome.
To understand genomics, we need to define genes and DNA. DNA is the genetic material that contains all the instructions a cell needs to function. But if a gene is a small portion of DNA, then a cell's genome is actually a warehouse of genes. A cell taps into only a small percentage of all the genes in the DNA warehouse at any time. Which genes the cell uses depends on its needs. For example, our skin cells can be thought of as being at rest most of the time, but if we are cut or burned, they become activated and hurl into action to repair the damage. This repair process is orchestrated by genes that were dormant but became active on injury. Thus, skin cells at rest would be drawing on a different constellation of genes than those performing repairs.
Similarly, a breast cell would use a different set of genes than a lung cell. To relate this to cancer, a breast cancer would use different genes than a lung cancer would because the two arise from different cell types. But even two breast cancers could employ different genes: a fast-growing breast cancer would use some genes that are distinct from those used by a slow-growing breast cancer (genes that direct the cell to grow fast would be more highly used in the fast-growing cancer). One can continue this line of thought down to the individual. Since no two people are alike, in personality or in DNA, no two cancers are genetically identical. Each cancer retains the genetic uniqueness of the affected person. This genetic uniqueness or cancer signature can be captured and measured on a gene chip" that is the size of a dime.
Cancer signatures are revolutionizing cancer research and will soon drastically improve our ability to estimate prognosis for each patient and tailor specific treatments to that patient's cancer. So it merits repeating. We can rapidly analyze the many thousands of genes that exist in any cancer today. This incredible technology is enabling researchers to classify cancers by their genetic signatures and to determine which signatures portend a good prognosis and which indicate a significant chance that a cancer will return. Cancer signatures are also being developed to help guide the best and most effective treatment choices for any cancer.
For example, a one-centimeter (one-third-inch) breast cancer with cancer signature A may be easily cured with surgery, whereas a onecentimeter (one-third-inch) breast cancer with signature B may have a high likelihood of causing a future cancer relapse if treated only with surgery and radiation. The first clinically approved genomics test, called Oncotype DX, helps oncologists estimate the chances that an early stage, invasive breast cancer will relapse in another part of the body (form metastases) as well as which patients would benefit most from chemotherapy.
Breast cancers that do not involve axillary lymph nodes and that make the estrogen receptor or progesterone receptor are eligible for Oncotype DX testing. By probing the activity of twenty-one genes in a breast cancer specimen (obtained from a small piece of the stored remainder of the original surgical specimen), a recurrence score" is generated that places the cancer in a low risk (6.8 percent), intermediate risk (14.3 percent), or high risk (30.5 percent) of developing distant metastases within ten years.
The recurrence score is also used to guide the choice of therapy, as follows: those in the low-risk range derive little benefit from chemotherapy and would typically be treated only with hormone therapy, whereas those in the high-risk category derive great benefit from chemotherapy (a 28 percent reduction in the risk of a cancer recurrence at ten years). There is uncertainty, however, about how best to treat those with an intermediate risk score, which is why this group of patients is the subject of an ongoing clinical trial called TAILORx. In this study, patients with intermediate recurrence scores are randomized (randomly chosen by a computer) to receive either hormone therapy or chemotherapy plus hormone therapy. The goal is to determine whether chemotherapy prevents a cancer recurrence and improves survival compared to hormone therapy alone in this group of breast cancer patients.
Gene-based tests like Oncotype DX are being developed for nearly every type of cancer, with cancers of the lung, colon, and prostate furthest along. The future of cancer diagnosis will increasingly operate like this: the pathologist will make the diagnosis, and the medical oncologist or surgeon will order genomics testing of the specimen to help determine both prognosis and the optimal treatment for that cancer. The hope is that genomics testing will allow us to tailor cancer treatments specifically to each individual case.
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