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Basser Center for BRCA Breakthroughs and Discoveries Panel  

by Tara Haarlander

At the 3rd Annual Basser Breakthroughs and Discoveries Panel, we had the pleasure of hearing from four expert scientists on the latest BRCA research and how it might affect patient treatment in the future. This summary covers a few of the more impactful points discussed. Some of the discussion focused on exciting new ideas and trials, while some generated even more questions. All of the panelists emphasized how critical it is to have the most current and reliable information possible when considering your own personal health situation.

Panel:

Moderator:

  • Susan M. Domchek, MD
    Executive Director, Basser Center for BRCA

Panelists:

  • Lewis Cantley, PhD
    Weill Cornell Medical College
    Cornell University
  • Steven Narod, MD, FRCPC, FRSC
    Women’s College Research Institute University of Toronto
  • Roger Greenberg, MD, PhD
    Perelman School of Medicine
    University of Pennsylvania

PI3 Kinase

Lewis Cantley, PhD, discussed his work on PI3 kinase, an enzyme that was initially discovered as an important part of the insulin signaling pathway.  He was surprised to discover that PI3 kinase physically binds to oncoproteins that can change a normal cell into a tumor cell. He went on to point out that insulin resistance is correlated with an increased risk of breast cancer, and that the amount of insulin receptor is increased in breast cancer cells compared to normal breast cells. When people eat sugar, their insulin levels increase, causing any cell with insulin receptors (including tumor cells) to take up glucose from the blood. Since glucose is food for cells, you could actually be feeding your cancer cells. 

PI3 Kinase bottom line 

Eliminating dietary sugar can be an easy and healthy way to lower your risk of cancer, and/or fight cancer once it is diagnosed. Plus, there are no negative side effects other than the obvious depression when you have to pass up that piece of cake!

PARP inhibitors

PARP inhibitors are still a very hot topic, and the panel reviewed why they are so effective for BRCA mutation carriers specifically. Both PARP and BRCA proteins work to repair DNA damage and prevent cells from becoming cancerous; however, they work on different types of DNA damage (single strand vs double strand breaks).  Giving a patient a PARP inhibitor can cause a buildup of DNA double-strand breaks in cancerous cells, leading to the death of those cells, unless BRCA steps in to fix it.  If the patient has no functioning BRCA protein (i.e., they are a BRCA mutation carrier), then the cancerous cells die. Success!

PARP inhibitor bottom line 

  • PARP inhibitors are a great example of basic scientific research leading to effective clinical intervention. 
  • It is critical to know as much genetic information about yourself as possible, especially if you have had a cancer diagnosis.  It can make all the difference in getting you the right treatment.

One question posed was whether or not PARP inhibitors could be used for cancer prevention.  The answer given was that there is concern that if used for prevention, PARP inhibitors could lead to accumulation of DNA damage in some cells types such as bone marrow, which could ultimately lead to hematological cancers.  However, the use of PARP inhibitors for cancer prevention is not out of the realm of future possibilities.  Let’s look forward to more on that someday.

Cancer Prevention

Dr. Steven Narod had a lot of interesting comments about cancer prevention. He pointed out that BRCA mutations do increase a person’s risk for breast, ovarian and related cancers; however, he also cautioned against viewing a mutation as a “Pandora’s box.” He said that our focus should be on prevention of breast and ovarian cancer: “these are the ones to beat.”  He also said that procedures for breast reconstruction after a preventative bilateral mastectomy (PBM) have dramatically improved, allowing women to be happier with their results—PBM is currently the only way to reduce a patient’s breast cancer risk to below the risk of the general population. Dr. Narod’s hope is to find other, non-surgical prevention options that are just as good as a PBM in reducing breast cancer risk.

Another question that popped up was, “How do you measure cancer prevention”?  Since there are currently no good biomarkers for breast or ovarian cancer, we cannot detect these cancers at an early stage (for example by a blood test), nor do we have anything to gauge the level of prevention after a “risk-reducing” treatment. For example, monitoring CA125 (for ovarian cancer) is extremely unreliable. As research continues, we hope to be able to report new and reliable biomarkers in the future.

Cancer prevention bottom line

  • Surgical intervention still remains the most effective prevention tool for high-risk patients, but the hunt for new options is still on. 
  • Finding more reliable biomarkers will be essential for early detection and measuring the effectiveness of new prevention options.

Immunotherapy

Also discussed were immunotherapies, or therapies that use the body’s own immune system to fight disease. Although immunotherapy has been revolutionizing the treatment landscape for melanoma and lung cancers, it has been much less so for other cancer types. This is due to immunotherapies being much more effective in cancers with a higher mutational burden or a lot of different mutations instead of just a couple. For both melanoma and lung cancer, this makes sense, since skin and lung cells are exposed to a host of agents that cause mutations throughout a person’s lifetime. However, a subset of breast and colorectal cancers may now be candidates for immunotherapy, with the hope that someday immunotherapy would also be useful for cancers with few mutations. It would be very exciting to add immunotherapies to our toolbox in fighting hereditary cancers!

Immunotherapy bottom line

  • Immunotherapies have done great things for melanoma and lung cancers, due to their effectiveness in treating cancers with high mutational loads. We are now seeing certain kinds of breast, ovarian, and colorectal cancers that may also be treated in this way, which hopefully indicates that new immunotherapies could be successfully applied to other types of cancer as well.

Conclusions

It is clear that research on hereditary cancers is moving ahead at an astounding rate, but there is still a long way to go. The Basser Research Center for BRCA is at the forefront of this research. Doctors will need to work very hard to keep up with the latest breakthroughs, and patients will find themselves navigating a tricky, ever-changing landscape. FORCE aims to provide the most current resources available and to help patients receive the best care possible. 

Posted 07/01/17

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