Advances in genetics give doctors new tools to customize treatments for their patients

Advances in genetics give doctors new tools to customize treatments for their patients

February 28th, 2016 by Steve Johnson in Local Regional News

Pathologist Dr. Sanford Sharp poses for a portrait in front of a projected slide of a magnified high grade carcinoma at Memorial Hospital on Feb. 18 in Chattanooga. Sharp leads a weekly breast cancer Tumor Conference, where a group of care providers review scans and images to determine courses of treatment for cancer patients.

Photo by Doug Strickland /Times Free Press.

“We are able to tell patients in advanced stages of lung cancer that we think you're going to be around for years rather than months”
Dr. Suresh Ramalingam
It is 7 a.m. on Thursday in a midsized conference room on the fourth floor of CHI Memorial hospital's MaryEllen Locher Breast Cancer Center.

In the next hour and a half, the 15 doctors, technicians, nurses and social workers gathered around the U-shaped table will make decisions that may determine whether a dozen patients live or die.

This is the weekly Tumor Conference, a meeting of the best breast cancer experts in the hospital, along with the technicians and support staff who perform the tests and imaging that enable the doctors to determine how best to treat their patients. The theory behind the meeting is simple: If everyone is in one room, there is an opportunity for debate and each member of the team has access to the same information.

Chief Pathologist Dr. Sanford Sharp begins by showing a slide of an ultrasound image on a large screen that fills half of one wall. The patient's physician, Dr. Maurice Rawlings, gives the group details of her situation:

"She's 30 years old and she had the audacity to do a breast self-exam. I slapped her hands and asked her what was she thinking," Rawlings said, to smiles and laughter from around the room. The American Cancer Society recently recommended against women doing self-exams, saying they are of little value.

But many cancer doctors disagree, and this case seems to prove their point: the tumor is real.

Rawlings points out the mass of malignant cells on the slide, a vague white blob.

The biopsies are worrisome, he said.

The patient has no family history of cancer, but that doesn't mean the cancer is not due to an inherited genetic flaw.

"You can bet there are bad genes there," one doctor concludes. "She's got something screwy in her DNA causing this to happen."

Another doctor recommends chemotherapy, but Rawlings counters with a question: "Will [the tumor] be impacted by chemo? What data do we have to believe or hope?"

"It's a tool, not a prophecy," another doctor responds.

The debate goes around the room for another five minutes, with half a dozen doctors questioning Rawlings about his proposed treatment.

Finally, there is a recommendation: a mastectomy — surgery to remove the breast — and radical reconstruction.

Then an ultrasound image for the next case flashes on the screen. In an hour, about a dozen cases will be discussed.

This is not a "cancer court"— no vote is taken, nor are the recommendations binding on the women's doctors. The meeting just allows them to bounce their ideas off the hospital's top cancer specialists.

But in this meeting — and in a similar one at Erlanger a few blocks away — one trend is apparent: Advances in genetic testing increasingly are allowing doctors to customize treatment plans to each patient's type of tumor.

The scientific progress is truly groundbreaking.

"It is a lot more exciting to be an oncologist today," said Dr. Suresh Ramalingam, deputy director of Emory University School of Medicine's Winship Cancer Institute in Atlanta. "We are able to offer patients more therapies and more opportunities to benefit."

The key has been unlocking the human genome, the underlying code in each cell. The Human Genome Project, which took 10 years and cost some $3 billion, was only completed in 2000 in draft form. Yet today, the DNA of a breast cancer patient's tumor can be analyzed for $3,000 to $4,000 in two to three weeks.

It is a dramatic improvement from the early days of cancer treatment.

"A hundred years ago, tumor classification was done with a ruler," said Memorial's Sharp: "'You've got a big one, that's bad; got a small one, that's good!'"

Microscopes helped doctors get a closer look, but classification was still largely based on shape and color with no real understanding of what lay underneath.

The discrepancies between individual cases were puzzling.

"If you have two women with breast cancer, they can behave very differently," said Erlanger hospital medical oncologist Dr. Larry Schlabach. "You may find that the one with very little cancer has already spread to the liver, while another with a breast full of cancer — it doesn't spread anywhere."

Having the ability to understand the DNA of each mutation helps explain how that happens. What researchers have learned is that any type of cancer may be caused by many different mutations. With lung cancer, for example, there may be 10 to 12 different major mutations, according to Emory's Ramalingam.

Researchers now focus on finding out how that mutated cell works — what it needs from its surroundings to survive or grow — and then try to develop a drug that will block the cancer cell's access to those resources.

Traditional chemotherapy uses a shotgun approach, blasting away at both healthy and cancerous cells. But the new approach, often termed precision medicine, aims only at the cancer cells.

"Think of the mutation as being in the driver's seat of the cancer," Ramalingam said. "They hit the driver and take him or her down, then the cancer has no ability to continue to grow and metastasize and go to other organs. But if you don't know who the driver is, then you have to bomb the hell out of the bus."

One of the earliest successes was with a mutation known as HER2, responsible for about a fourth of all breast cancers, and the drug developed to fight it, marketed as Herceptin.

"In the history of [cancer drug testing], you typically will get a 10 percent response rate," said Sharp. "But Herceptin was off the scale — if a patient had the HER2 positive mutation, it would respond almost every time."

"HER2 cancers were the worst of all," Schlabach said. "But in the last month, I have had four patients with advanced cancers in the breast and lymph nodes, gave them [Herceptin] before they went to surgery, and they came back with no cancer left in the breast."

Researchers are reporting similar success in other major cancer groups, primarily lung, colon, and melanoma cancers. For example, doctors now have drugs that target three mutations that make up about 22 percent of all lung cancer cases, according to Ramalingam.

Now that researchers understand that cancers include many different mutations, the challenge is to find the drugs or combination of drugs that target them.

That process has improved in recent years, according to Dr. Carlos Arteaga, director of the Vanderbilt-Ingram Cancer Center's Center for Cancer Targeted Therapies. "In the old days, you would have a proposed drug for breast cancer, so you would include everyone who had breast cancer in the sample, and if it only worked for 5 percent of the cancers, we called that drug ineffective and threw the drug away," he said.

Today, researchers realize that the 5 percent of patients where the drug worked may have been the ones with a specific mutation it targeted. So current tests are focused on patients with the same mutation, and not breast cancer in general.

One current research project, for example, includes 30 groups of 35 patients, each with a mutation specific to that group.

"You do a trial in patients with X mutation," Arteaga said. "Thirty percent have a magical response never seen before in the history of the world. Do you need another trial? Not really."

The federal Food and Drug Administration, which must approve new cancer drugs, has generally agreed, particularly since many of the patients have Stage 4 cancer with few other options.

"The FDA has accelerated their processes, and drugs are being brought to the clinic much faster," Ramalingam said.

Cancer specialists emphasize that while progress has been rapid for specific cancers, there is still a long way to go before cancer can be treated as a chronic illness such as diabetes, where a patient might take a pill once a day to control the disease.

"An individual cell is extremely complex, and from one person to the next different things happen," Schlabach said.

But most cancer researchers and doctors are optimistic.

"Cancers are accumulations of mutations, and we don't necessarily have a drug for many of them yet," Sharp. "But I think with time there will be a whole pharmacy of drugs for specific mutations."

"We are able to tell patients in advanced stages of lung cancer that we think you're going to be around for years rather than months," Ramalingam said. "And if we keep you alive for a few more years, by then we may make lung cancer more a chronic disease than a killer disease."

"Patients are living longer and cure rates are getting better, although we still have a long way to go," he added. "We don't have something for every patient, but we are heading in that direction."

Contact staff writer Steve Johnson at sjohnson@timesfreepress.com, 423-757-6673, on Twitter @stevejohnsonTFP, or on Facebook, www.facebook.com/noogahealth.


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