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.