You read a lot about personalized cancer therapy both in scientific journals and in the general press. The idea is that in the (near) future doctors will be able to learn a lot more information about your tumor, and pick just the right therapy to give you the best outcome.
You need three kinds of things to be able to do this:
- molecular targets – think of them as Achilles’ heels in the cancer’s biology that allow you to take it down while leaving normal cells alive
- drugs that hit those targets
- tests that tell you whether the targets are in the tumor
That last one is an important element in translating the knowledge that is gushing out of the world’s DNA sequencers’s and the drugs being developed. We need reliable, accurate and rapid tests for genomic changes in tumors. I want to tell you about a trial that I joined at MD Anderson that is testing how good we are at doing just that.
There have already been some notable successes in getting molecular markers into the clinic. In breast cancer the discovery and targeting of the Her2 oncogene (http://en.wikipedia.org/wiki/HER2/neu) is a remarkable example. People whose breast cancer has the Her2 oncogene, which stimulates the cancer cells to grow, can be treated with herceptin, and this markedly improves outcome. Even more fundamental in breast cancer is the use of endocrine therapy for tumors that are hormone positive. If the cancer is ER+/PR+ tamoxifen and aromatase inhibitors are used long term to suppress the signal for growth that comes from estrogen and progesterone.
What is perhaps less often discussed is that the clinical application of these breakthroughs is still commonly based on very traditional diagnostic tools. ER/PR status is measured with antibody staining of paraffin sections. Similarly Her2 is first tested with an antibody, and an in situ hybridization to measure DNA amplification is only used if the antibody test is equivocal. That was the situation with my tumor – high levels of easily detected ER, ambiguous Her2 by antibody which was then ruled negative because there was no evidence of DNA amplification. Paraffin sections are made from fomalin fixed tissue – this is a great way to preserve tissue architecture, allows staining of the resulting sections with blue and red dyes and has formed the basic tool kit for pathology for over a 100 years. The problem is that formalin damages the nucleic acids DNA and RNA where much of the data we want to look at today – the fruits of the genomic revolution – are found.
The trial I joined, “Feasibility, Validation and Implementation of Genomic Testing for Chemotherapy and Endocrine Sensitivity of HER2 Negative Primary Invasive Breast Cancer (Clinical Stage I to III)” (http://clinicaltrials.gov/ct2/show/study/NCT01334021) takes existing technology for examination of genomic changes, and applies it to tissue from 300 patients that is prepared in a way that is suitable for nucleic acid analysis. The genomic data found will be layered on the traditional variables – ER/PR, Her2 and lymph node status – as shown in the diagram to generate 4 groups. The “prediction” here comes from the processing of the genomic data through an algorithm.
Since this is a feasibility study, the “prediction” will not be used to determine treatment for me or the others in this trial. It’s kind of a practice run – the focus is actually on whether it is possible to routinely do this kind of analysis in a clinical setting. The goal is to have 85% or more successful tests – meaning tests that give a interpretable result. At the same time patients will be followed for 5 years, to see how they were treated and how they did, and this will allow the researchers to test the value of the predictions. The results will form the basis of the next trial. If all goes well, then the next trial will perhaps use this style of genomic analysis to make treatment decisions and see if this improves outcome for patients.
So you could say that this work will not benefit me personally, and that is likely (you never know…). Then again, all it required was some biopsy material and the promise to stay in touch over the next 5 years. The benefits to people who are diagnosed 5 years from now could be huge.
Get the best treatment for yourself, today. Participate in research for your kids, tomorrow.
Entering a World of Pink 