An NCI-designated Comprehensive Cancer Center
By Abe Rosenberg | November 9, 2017
What if you could find out, 10 years in advance, that you had a strong likelihood of developing a particular type of cancer? Would you want to know? 
The exploding field of cancer genomics is enabling that kind of prediction for a growing number of inherited cancers, like identifying one of the many genes beyond BRCA1 and BRCA2 gene mutations linked to breast cancer. 
Most cancers are not inherited. They happen because of damage to the genes in our tissues, often by environmental interactions and health habits, like smoking or obesity. 
Nevertheless, we are all born with genetic mutations that came from our parents, and scientists are rapidly gathering genetic data that could have implications for millions more of us. Thanks to advanced technology, researchers are discovering and identifying many additional gene mutations and their associated cancer risks, and the pace is accelerating. 
In other words, a tidal wave of cancer-related genomic information is at our doorstep. 
But are we ready for it? Will doctors everywhere be able to access and interpret it all? Will they have the skills to properly educate and help their patients?

Moving Fast

“The pace of change in just the last five years has been extraordinary,” said Jeffrey Weitzel, M.D., director of City of Hope's Division of Clinical Cancer Genomics. “The genetics we typically teach in medical school is inadequate for today.”
“Cancer genomics is moving so fast that the old lessons quickly become obsolete,” agreed Kathleen Blazer, M.S., Ed.D., associate director of City of Hope's Cancer Genomics Education Program. “We need to find ways to train the medical workforce around the world.”
City of Hope has stepped up to do just that, running perhaps the largest and most comprehensive genetic cancer risk assessment in the country. It aims to stay ahead of that vast knowledge curve, giving clinicians – doctors, physican assistants, nurses, genetic counselors and others – the tools and information they need to take better care of their patients. The program has enrolled over 700 medical professionals in all 50 states and 25 countries.
Jeffrey Weitzel Jeffery Weitzel, M.D.
At the heart of the program is an intensive, multiweek training course in cancer genomics that can be taken online or in person. But that's only the beginning. Graduates join a Clinical Cancer Genomics Community of Practice, an electronic gathering place to share ideas, get updates and hash out difficult case issues. An annual Genomics Conference, a kind of “boot camp,” operated in collaboration with the University of Chicago, helps keep medical professionals up to date.
The experience can be invaluable, and also a bit overwhelming for participants.
“They come up to me,” said Blazer, “and exclaim, 'I didn't know what I didn't know!'”
“The best compliment I've received,” concurred Weitzel, “came from oncologists and surgeons who told me, 'I'm now more uncertain than ever!'”

Very Big Data

That uncertainty stems from the sheer vastness of the available information, as well as its growing complexity. The first human genome took 10 years and $3 billion to sequence. Now, with ever-more-sophisticated next-generation tools, a human genome can be sequenced in one week at a cost of about $1,000. Where once doctors screened for mutations in a single gene at a time, they can now order a “panel,” examining dozens of genes known to be associated with higher cancer risk.
But once the information comes in, special training is needed to properly interpret it.
For example, not every mutation is an automatic red flag for cancer. Some, like the BRCA mutations, do indicate a significantly elevated risk, but others are less clear; they may point to only a slightly, even clinically insignificant increase in risk. 
“Do we tell patients that their gene profile indicates an 11 percent chance of breast cancer as opposed to the normal 10 percent?” asked Weitzel, thinking out loud. “Is that truly useful information?”
Still other genetic test results carry even greater mystery. They're called variants of uncertain significance because it's simply too early in our learning curve to know whether or not the typically minor genetic change disturbs the function of the gene, or whether it is simply a rare variation of “normal.”
Kathleen Blazer Kathleen Blazer Ed.D.
“The more data we collect on these mutations,” said Blazer, “and the more we're able to correlate it with family histories, the more answers we'll get.” City of Hope plays a key role in this task as well, having collected data from 18,000 patients over the past 20 years. Then using that data to create a cancer registry that involves partners in medical facilities across the country.
“We need to realize that right now we're ahead of ourselves,” said Blazer. “We have access to so much information but we may not always know how to grapple with it. We may be scratching our heads for a long time. What the training and the Community of Practice do is reassure clinicians that they're not alone,” and critically provides practice support tools and forums to discuss state of the art care.

A 10-year Head Start

But how to reassure patients, many of whom still fear testing because of the “bad news” they may hear? 
“My field has changed a lot,” said Thomas Slavin, M.D., a City of Hope clinical geneticist who works with patients and their families. “It wasn't that long ago when patients got tested under assumed names because they worried about losing their jobs or jeopardizing their insurance.” A 2008 law made such discrimination illegal. But some patients still resist testing because of their mistaken belief that a positive test is a dead end: that there's little they can do.
“We don't believe that!” insisted Weitzel. 
“To us, a positive test means we get a 10-year lead time on a possible disorder, giving us plenty of time to head it off.” 
Getting that 10-year lead time creates an even greater opportunity for the patient's children who may inherit the same mutation.
“What I really enjoy doing,” said Weitzel, “is being able to tell a mom with breast cancer who's worried about her daughters that we have a whole lifetime to help them, to modify, to combat, to prevent. That's very exciting.
“It's a 'kinder, gentler' approach to prevention.”
And it’s an approach with more tools than ever before.

What’s Next

Because of all the publicity surrounding the case of Angelina Jolie (who inherited the BRCA mutation and chose to have a double mastectomy) some patients may believe surgery is their only solution. It's not. Patients can get more frequent mammograms and MRIs to spot tumors early. They can also benefit from chemo prevention: taking cancer-killing drugs like Tamoxifen to stop tumor cells from ever developing.
“In one study we used a nasal spray to deliver medication that temporarily shuts down a woman's ovaries, reduces hormone exposure and reduces breast density, minimizing the risk of cancer,” said Weitzel, also pointing out that this “medical menopause” is well tolerated because of low-dose hormone support. Reversible ovary function resumes after treatment is completed.
Thomas Slavin Thomas Slavin, M.D.
Even more exciting is the potential for gene-based targeted therapy drugs to alter the mutations themselves, perhaps shutting off the cancer-causing process altogether. Already researchers have identified many such “actionable” mutations. Could this be the flip side of the genomic knowledge explosion?
“Not the flip side,” said Weitzel. “That's the 'A' side! This is what it's all about!”
And that's why, with the right training and the right attitude, cancer genomics will eventually be integrated into every medical practice, giving clinicians and their patients more information than ever before, with more and better opportunities to ward off cancer and live a long, healthy life.
“We need to retain our humility in terms of understanding what we know and what we don't know.” said Blazer. “And we need to remember that what we don't find today, we may find tomorrow.”

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