Breast Cancer Prognosis Predictor Determines Survival Rate

Many women who have breast cancer legitimately complain that treatments are as bad as the disease. A new method of predicting the prognosis of breast cancer, however, can tell women and their doctors whether a side effects-prone method of treatment is likely to lead to remission from the disease.

The Predictive Power of Metagenes

The new understanding of treatment outcomes in breast cancer stems from an observation that groups of genes, known as metagenes, tend to be "switched on" together in different forms of cancer. Prior research had found that in every form of cancer, there is a period in which chromosomes, the long strands of DNA in the nucleus of every cell, tend to be uniquely unstable and prone to making errors in the coding of proteins that the cell makes to regulate itself.

In addition to chromosomal instability, in different kinds of cancer, there is also a period of "mesenchymal transition." This fancy term refers to a period in which cancer cells become "unglued" from the tissues in which they were created and migrate to other parts of the body. Cancer cells feed on more and more sugar and have to absorb more and more sodium. Sodium ions are positively charged. This builds of a positive charge inside the cancer cell that neutralizes the negative charge on its outer membrane that keeps in anchored in place.

And scientists are also aware of metagenes that regulate a process called lymphocyte-specific immune recruitment. It's natural for the immune system to attack cancer cells, but some cancer cells develop methods to deactivate the specific white blood cells that would destroy them.

These three characteristics of metagenes apply to most kinds of cancer that form solid tumors. Of course, they aren't the only genes that scientists measure to assess the value of treatments for cancer.

Cancer Biomarkers and Choosing the Right Therapies

For several decades, doctors have been able to measure specific kinds of protein "biomarkers" to determine whether a specific treatment would be beneficial for a specific patient.  A biomarker is a specific protein that appears in blood, tissue, or body fluids that only occurs during a specific disease process. Probably the best-known cancer biomarker in breast cancer is ER, the estrogen receptor marker, which tells whether or not breast cancer growth is fueled by estrogen, and whether estrogen-receptor antagonists, drugs such as tamoxifen, which prevent "docking" by estrogen on breast cancer cells, might prevent the progress of the disease. Other breast cancer biomarkers include:

• HER-2, human epidermal growth factor receptor 2, which indicates whether blocking the growth of breast tissue might stop the disease, and 
• BRCA1 and BRCA2 markers, which tell women and their doctors whether they have genes that repair breast cell DNA and prevent cancer.

The new, metagenetic predictive algorithm does not replace these older tests. It only gives doctors additional information about the staging of cancer, telling them whether the emphasis should be on preventing the mutations that lead to new cancers, or stopping the spread of already-existing cancer beyond the breast, or bolstering the immune system so it can fight cancer even though it has already spread.

Reading Breast Cancer's Signature

 In simplifying the explanation of how the new predictive method of making a breast cancer diagnosis works, it's easy to miss just how big an achievement the algorithm really is.  Breast cancer is the result of just one defective gene, or 10, or 20. The researchers at the Columbia Initiative in Systems Biology had to assess the activity of hundreds of genes on the progress of breast cancer, and then locate the top hundred, and finally just four metagenes that tell whether a treatment is likely to work or not.

Timing Is Everything

The Columbia University researchers also added insight into the understanding of all kinds of cancers by showing the sequence in which events occur in cancer. The activation of a cancer inducer gene, it turns out, makes a big difference in predicting future survival before the cancer organizes itself into a tumor, but not so much after the tumor breaks out of the connective tissue of the breast and begins to spread to other organs.

The activation of a mitotic instability gene doesn't do a lot for  the development of cancer, but it makes a big difference in "how cancerous" a cell becomes, how abnormal it looks under the pathologist's microscope.

Then a "breakout gene," the mesenchymal transition metagene that determines how well a tumor stays "stuck" in the tissue where it formed, is the best predictor of survival from the cancer. In breast cancer, the breakout gene is activated in stage I, when they tumor is still in the breast, but in some other forms of cancer, such as ovarian cancer, it is not activated until stage III, when the tumor has spread to nearby lymph nodes. And finally, survival becomes a matter of how the tumor interacts with the immune system. The ability of the tumor to "fool" white blood cells regarding its cancerous nature has a great deal with how long a woman will live after the tumor has begun to spread.

Different metagenes have different prognostic meanings at different stages of the disease. But how can this information help women live longer and better after a breast cancer diagnosis?

Using Genetic Testing for Better Treatment Decisions

Although this new mathematical model of which women will live longer on the basis of their genetic signatures is the best of its kind, it's not perfect. The mathematical model is accurate just with regard to the question "Which woman will live longer?" only about 75% of the time. And there is nothing in the prognostic model that gives a hard and fast answer to questions of how long a woman will live, whether a given treatment absolutely will work or absolutely won't, or whether the side effects and cost of treatment are really "worth it," as only women with breast cancer can judge for themselves.

Genetic testing is useful for reading the overview of breast cancer. It's good to know whether the cancer is in a stage where preventing new changes in DNA is essential, confining or removing the tumor is key to survival, or it's time to look for ways to bolster the immune system. But the specifics of cancer treatment absolutely are not dictated by this new test. That's still something for women and their doctors to decide.