day 301 – why joining tissue studies is vital to ushering in the era of personalized cancer therapy

Earlier this week I blogged about the cancer conference, the WIN Symposium which I attended last week. I summarized some of the current challenges in developing personalized cancer therapies, including the complexity of cancer. The good news is that there are many institutions and companies that are engaged in this fight, and are working hard on the challenge. But they can’t of it without the help of the cancer patient.

So, what can you as a cancer patient, do to help smooth the path towards molecular medicine? Simple: join some tissue trials, donate your cancer tissue and provide the important materials needed for this research. There is a lot of research going on, and all of these projects need tumor tissue.

The research protocols I am talking about are sometimes called trials, are routinely listed in ClinicalTrials.gov but they are not tests of therapeutics or diagnostics. As the consent forms of such trials point out, participation is not primarily designed to benefit you and the data generated may well not be used by your doctors to make clinical decisions about you. Instead, they are primarily altruistic, as the work is most likely to benefit future cancer patients. I like think about the people who participated in trials that were used to develop the treatments I received. We owe a debt to those who came before, and need to act today so that those who come after have it better.

But, although joining these protocols will not change the treatment plan for my cancer, I do believe that I receive a benefit from participating: it is part of what being a cancer survivor is to me – someone who accepts that the fight against cancer is now part of my life, and who does things to fight the disease. By providing my tumor materials to research studies I am being active in this fight.

So what kinds of trials are these? I joined three, and here they are:

1) Molecular Testing for the MD Anderson Cancer Center Personalized Cancer Therapy Program

This is a trial for any advanced cancers, is an MD Anderson-only protocol and plans to accrue 5,000 patients. It is one of the main tissue accrual trials for the Institute of Personalized Cancer Therapy at MD Anderson, and the principal investigator is Dr. Funda Meric-Bernstam, the Scientific Director of the Institute. The trial’s purpose is (from the listing on ClinicalTrials.gov):

“[…] to perform standardized testing to determine which different genes are mutated (have gone through changes) in cancer patients to provide them with personalized cancer therapy. A patient’s doctor may be able to use testing information on their tumor to identify clinical trials that may be most relevant to them.”

So the data from this trial could lead to the selection of a trial of a targeted therapy, but also may not. In my case, for example, the standard of care is often effective and so the pressure to go to a front-line therapeutic trial (i.e. before recurrence) is not high.

The description continues:

“Another goal of this laboratory research study is to learn how often different genes mutate in patients with different cancers. Researchers will also use the information learned from this study to develop a database of the different kinds of mutations in cancer-related genes.

Researchers also hope to better understand how mutations in cancer-related genes may affect a patient’s response to different therapies. Researchers can use this information to select specific therapies for future patients that are more likely to be effective.”

These parts are pure research. What they learn from the tissues they gather could help inform future decisions.

2) Feasibility, Validation and Implementation of Genomic Testing for Chemotherapy and Endocrine Sensitivity of HER2 Negative Primary Invasive Breast Cancer (Clinical Stage I to III)

This study is also a registry trial, meaning that the 500 patients to be accrued will be followed for clinical outcomes, in this case for 5 years. It is a breast cancer-only and MD Anderson-only protocol. The goal of this work is to see if markers can be identified that will allow doctors to predict who will respond to current treatments. The principal investigator is Dr. Stacy Moulder.

Given that my tumor ignored the taxol and was only moderately dented by FAC, perhaps such a capability would have saved me some unnecessary chemo? Here is the purpose statement (from ClinicalTrials.gov listing):

“The goal of this research study is find out if researchers can use genetic testing on tumor samples to predict if tumors will respond to breast cancer treatments. The tumor sample will be tested to learn if certain genes are activated (turned on) in the tumor. Researchers hope that the activation of these genes may predict if the tumor will be sensitive or resistant to routine breast cancer treatments, such as chemotherapy or hormonal therapy.”

The technology used is gene expression analysis, and has been used extensively to profile tumors, and subdivide categories of tumors that appear uniform by conventional pathology into molecular subtypes – looking under the hood, so to speak. Again, what is learned here may allow future patients to avoid unnecessary treatment. Remember that chemo and radiation are not wholesome therapies – they bring significant risk of secondary cancers aside even from the side effects many of which can be profound and prolonged.

3) Prospective Follow-up of individuals Who are at Increased Risk for Developing Breast Cancer

This trial is not listed in ClinicalTrials.gov, and is another MD Anderson specific protocol, led by Dr. Banu Arun. The goal is to develop a blood test that can be used to monitor people at high risk of developing breast cancer, such as people with several close relatives with breast cancer or genetic predisposition. Such a test might be able to give warning even before things show up in a mammogram. In the future this might allow women like say Angelina Jolie to monitor her breast health with a blood test rather than have preventive surgery, of course if it can be proven that the early warning given by the test is sufficient to allow effective prevention.

It seems a little odd to include patients with cancer in such a test, but you need to have samples from people with cancer – the marker being tested should be present in these samples. It should then disappear once you are past-treatment with “no evidence of disease”.

Another reason for including patients is that the test could also be used to monitor treatment effectiveness and give early warning of a recurrence. Of course, as a breast cancer survivor you are by definition at high risk of getting more breast cancer. For this protocol you will give blood for the test once a year for 5 years, while your breast health is monitored. Given that the 5-year survival of people with stage III breast cancer is about 70-80%, if you have 100 such patients in the trial, you’ll get 20-30 recurrences.

Here is what the consent document states:

“The goal of this follow-up research study is to monitor individuals who are at increased risk to develop breast cancer and check for any changes in their breast related health. By monitoring high risk individuals, researchers may identify certain factors that may play a role in breast cancer development in high risk individuals”.

So when I fell a little down, I like to think of my cancer tissue or blood being tested in these protocols, and my data ending up in a dataset that will lead to an advance agains the disease. Take that, cancer!