TIME Cancer

Genetic Test Impacts Chemo Choices In Surprising Ways

Maciej Frolow—Getty Images

A study investigates for the first time how a gene-based test is affecting women’s decisions to get chemotherapy

In the new era of personalized medicine, having more information on hand is considered the ideal situation for making more customized, and ideally, effective decisions about medical care.

And in a new study of breast cancer patients, researchers show that a relatively new genetic test for evaluating tumors is doing just that. It’s just that the test isn’t necessarily leading to the decisions that experts expected.

The Oncotype DX Breast Cancer Assay is a test approved by the U.S. Food and Drug Administration to help women decide how likely their breast cancer is to recur. The score, from zero to 100, is for women with breast tumors that have not spread to the lymph nodes. It places women on a scale of probability, based on an analysis of 21 genes in her tumor. Most doctors and patients use the score to decide, in part, whether the woman should receive chemotherapy following surgery.

MORE: A Major Shift in Breast Cancer Understanding

In previous studies, about 20% to 30% of doctors say they changed their recommendation about chemotherapy based on the Oncotype DX score. But none of the studies looked at how Oncotype DX affected the likelihood a woman would undergo chemotherapy rates in a real-world setting— outside of a trial. In clinics, says Michaela Dinan, assistant professor in medical oncology at the Duke Cancer Institute, many other factors contribute to treatment decisions, including fear, family history and physician advice. So she and her colleagues conducted a review of data on more than 44,044 breast cancer patients to see how the Oncotype test affected chemotherapy decisions.

MORE: Here’s the Amount of Exercise That Lowers Breast Cancer Risk

The results, published in JAMA Oncology, showed that overall, the test had no effect on their decision. Women who were tested were no more or no less likely to opt for chemotherapy than those not getting Oncotype DX. Younger age and a higher risk disease were more likely to predict chemotherapy use than the assay.

While many assumed that the test would lead to fewer treatments, Dinan’s data shows that how the testing affects chemotherapy decisions is less predictable. When Dinan delved further into the numbers, she found an interesting pattern. Those rated as having high-risk breast cancer according to the National Comprehensive Cancer Network guidelines were less likely to get chemo than women who were not tested. And among people with low-risk disease, those getting the genetic test were more likely to get chemotherapy than low-risk patients who did not.

Because the study did not take into consideration what the Oncotype DX scores were, it’s possible, for example, that women considered high risk who received intermediate or low Oncotype DX scores decided not to undergo chemotherapy since the testing showed their response might not be as positive as they might have expected. On the other hand, women who have low risk disease and receive an intermediate test score might decide to undergo chemotherapy since the intermediate risk might represent a slightly higher risk of recurrence than they were anticipating.

“It’s a more nuanced finding,” says Dinan. “The Oncotype DX test is impacting the receipt of chemotherapy, but the impact isn’t in one direction or another in terms of whether people are more or less likely to get chemotherapy.”

As more options for personalized treatments make their way into the clinic, Dinan says it’s worth remembering that they shouldn’t dictate decisions but inform them. “The nuanced finding of the difference between high risk and low risk patients says to me that whether or not a woman with early stage breast cancer undergoes chemotherapy is going to be affected by a number of different factors, not just this assay. It’s a personalized discussion about the individual patient’s case.”

TIME People

Marcy Borders, the Dust-Covered Woman in the Iconic 9/11 Photograph, Has Died of Cancer

She wondered if her exposure to the attack contributed to her illness

Marcy Borders, a survivor of the Sept. 11 terrorist attacks and the subject of one of that day’s most iconic photographs, died on Monday of stomach cancer. She was 41.

Her family first announced her death via Facebook early Tuesday morning.

On the morning of Sept. 11, 2001, Borders was one month into a new job as a legal assistant on the 81st floor of One World Trade Center. When American Airlines Flight 11 struck the building a few stories above her office, she fled, making it onto the street just as the adjacent tower collapsed. A stranger pulled her into a nearby lobby, where Agence France-Presse photographer Stan Honda took her picture: her face distraught; her body covered in ash. In the weeks and years following 9/11, the world would thusly know her as the “Dust Lady.”

Meanwhile, she found herself haunted by her experiences that morning, ultimately struggling with depression and substance-abuse issues.

“My life spiraled out of control. I didn’t do a day’s work in nearly 10 years, and by 2011 I was a complete mess,” Borders told the New York Post in June 2011. “Every time I saw an aircraft, I panicked. If I saw a man on a building, I was convinced he was going to shoot me.”

She checked herself into rehab in April 2011, eight days before President Obama appeared on television to announce the death of Osama bin Laden.

“The treatment got me sober, but bin Laden being killed was a bonus,” she told the Post. “I used to lose sleep over him, have bad dreams about bin Laden bombing my house, but now I have peace of mind.”

Borders was diagnosed with cancer last August. Speaking with the Jersey Journal a few months after her diagnosis, she ventured that her exposure to the pollutants emitted by the collapse of the World Trade Center may have contributed to her illness.

“I definitely believe it because I haven’t had any illnesses,” she said.

Read next: What We Can Learn From Behind-the-Scenes Photos of Dick Cheney on 9/11

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TIME longform

Tig Notaro Talks Topless Comedy and Standing Up to Ira Glass

The comedian's HBO special premieres Saturday

Most comedians work their way up the fame ladder little by little: a spot on a late-night show, a role in a comedy film. But a single smash-hit set launched Tig Notaro to stardom overnight.

That’s not to say the stand-up comic didn’t pay her dues: the Mississippi native spent years touring and doing small parts in comedy shows. Agents said she was “too low-key,” and she wasn’t mainstream enough to get booked on Leno or Letterman.

But after a particularly rough patch in her personal life—she got extremely sick with a C. difficile infection, her mother died, and she was diagnosed with breast cancer—Notaro gave a landmark performance at the L.A. nightclub Largo that was praised for its naked honesty about all she was going through, even while keeping the audience in stitches. Louis C.K. called it one of “a handful of truly great, masterful standup sets” he has seen in 27 years, and the news quickly went viral.

Notaro’s comedy may not be for everyone, but it has earned a loyal following. She’s had a red-letter summer: in July, she was the subject of the Netflix documentary Tig, which followed her post-cancer personal life, and on Saturday, HBO will air her comedy special Boyish Girl Interrupted, a set she closed out by taking off her shirt to reveal her double mastectomy scars. “It was really just part of the process of coming to terms with what my life was,” Notaro said in an interview with TIME. For the audience, though, it was that blend of funny, uncomfortable and slightly surreal that makes Notaro’s comedy so captivating.

TIME Cancer

A Major Shift in Breast Cancer Understanding

Getty Images

A new study shows that previous assumptions about early breast lesions called ductal carcinoma in situ, or DCIS, may have been off the mark

—Breast cancer experts have been in a tumult in recent years over something called ductal carcinoma in situ (DCIS). These lesions, usually very small, are starting to emerge more frequently in mammograms that are better able to pick out even the smallest aberrations in breast tissue. But cancer doctors aren’t agreed on how significant DCIS actually is.

Technically labeled as a stage zero cancer, some experts don’t believe they are tumors at all, but pre-tumors, since the growths have not expanded beyond the milk ducts. In fact, a National Cancer Institute working group in 2013 recommended that the name “carcinoma” be removed from DCIS to highlight the fact that the lesions aren’t quite malignant, and therefore may not need the more aggressive treatment that cancers would warrant.

MORE: High-Tech 3D Mammograms Probably Saved This Woman’s Life

But the latest study shows that thinking may be wrong. DCIS may not be as benign as doctors once thought.

In order to tease apart how a DCIS diagnosis and its treatment affects death from breast cancer, researchers reporting in in JAMA Oncology reviewed records from 108,196 women, the largest number yet in a study of DCIS. The large number was important to see if the number of deaths from DCIS made the findings statistically significant. Overall a diagnosis of DCIS was associated with a higher risk — 3% — of dying of breast cancer in 20 years compared to women who didn’t have the cancer. This risk was highest for younger women (diagnosed before age 35) and for black women.

But when the researchers looked more carefully at the women with DCIS, their rates of breast cancer recurrence and their death rates, they found that those getting surgery and radiation or just surgery did indeed lower their risk of getting a recurrent cancer, but did not reduce their risk of dying from breast cancer.

MORE: Here’s the Amount of Exercise That Lowers Breast Cancer Risk

That suggests that the DCIS may be not be pre-cancerous lesions, but more cancerous than doctors thought, says the study’s lead author Dr. Steven Narod, from the Dalla Lana School of Public Health at the University of Toronto. Surgery, surgery with radiation, and even mastectomy do nothing to lower the 3% risk of dying of breast cancer in 20 years once a woman receives a DCIS diagnosis. “These women are not dying of DCIS. They die the conventional way from breast cancer — because it spreads to the bones, liver and lungs. The women who die of DCIS died because their breast cancer already spread by the time they received treatment,” says Narod.

That’s a complete shift in thinking about DCIS. And could potentially result in a dramatic change in the way women diagnosed with DCIS are treated. If the results are confirmed, and treatments do not lower the risk of death from breast cancer, then would surgery, or surgery and radiation still be worth the side effects and complications of that these interventions carry? In an editorial accompanying the study, cancer experts from University of California San Francisco argue that radiation should not be routinely given to every woman diagnosed with DCIS and undergoing surgery to remove the lesion. More research, they say, is needed to find better ways to distinguish DCIS lesions, possibly by their genetic makeup, into those that are more or less likely to have spread.


Jimmy Carter Says His Cancer Has Spread to the Brain

Will begin radiation treatment on Thursday

President Jimmy Carter held a press conference Thursday to discuss his recent cancer diagnosis, revealing that he has melanoma in his brain.

The cancer was initially discovered in early August on his liver. Carter said Thursday that the melanoma tumor on his liver was removed August 3rd, but subsequent MRIs found four, 2 millimeter large spots of the cancer on his brain.

“I was surprisingly at ease,” Carter said of learning the diagnosis. “I’ve led a very wonderful life, an exciting, adventurous.. existence. So I was surprisingly at ease, much more so than my wife was. Now I’ll be prepared for anything that comes.”

Carter will receive his first of four radiation treatments Thursday afternoon, and will also regularly be administered medication to boost his immune system. There will be follow-up scans to search for more instances of the cancer elsewhere in his body.

He said he will scale back his commitments and involvements with The Carter Center, saying he will continue to work on fundraising and attend board meetings.

“I can’t really anticipate how I’ll be feeling obviously, I’ll have to defer quite substantially to my doctors,” he said.

When asked if he would have done anything differently looking back on his career, Carter said, “I wished I would have sent one more helicopter to rescue the hostages in Iran.” He was President during the 1979 Iranian hostage crisis.

Carter, 90, was the 39th President of the United States.

TIME Cancer

How Doctors Cured This Woman’s Brain Cancer

MaryAnn Anselmo Memorial Sloan Kettering
Christopher Morris—VII for TIME MaryAnn Anselmo in New York City on March 13, 2015

Earlier this year, TIME explored the promise of precision medicine in treating cancer patients. We featured one woman who was taking a drug typically used for melanoma to treat her brain tumor. Here’s an update on how she’s doing

In November 2013, MaryAnn Anselmo—who was on the cover of TIME in March—heard the words that most of us dread the most: she had cancer. Worse, it was stage 4 glioblastoma, a particularly aggressive brain tumor that often takes a patient’s life in a matter of months. Having just recovered from a devastating car accident, Anselmo thought, “Somebody wants me dead here.”

Nearly two years later, the New Jersey resident is receiving some completely different, and more welcome news. “The latest scan doesn’t show any tumor any more,” her physician, Dr. David Hyman, acting director of Developmental Therapeutics ad Memorial Sloan Kettering Cancer Center (MSKCC), tells TIME. The results from Hyman’s most recent study, which Anselmo participated in, is published in the latest issue of the New England Journal of Medicine (NEJM).

“I’m tired all the time,” she says, “but I’m dealing with it, living with it. I feel awesome compared to what this tumor could have done to me.”

MORE: The Cancer Gap

Hyman is reluctant to call it a “cure” for certain cancers—the burden of proof is higher than this one study or this one patient—but Anselmo’s cancer is gone. And for that, Anselmo can thank something called a basket trial, a new way for doctors to test promising cancer treatments that more precisely target the right therapies to the right patients at the right time. This is the first such trial of its kind.

The trial puts the idea of precision medicine to the test. At 23 cancer centers around the world, 122 patients with advanced cancer signed up for a last-resort treatment covered in the new study. All had their tumor genomes sequenced, so doctors could get a better sense of which mutations were driving the cancers, and whether there were any targeted therapies for those mutations.

Anselmo had three mutations fueling the growth in her brain, but she and her doctors at MSKCC decided to focus on one, called BRAF. A recently approved drug to treat BRAF mutations in melanoma helped shrink or halt tumor growth in half of treated patients, so doctors wanted to know whether the drug could help patients with the same mutation but with different kinds of cancer, like Anselmo. But while BRAF mutations occur in about 50% of melanoma cases, they are much rarer in other types of cancers. So creating a trial for patients like Anselmo would take both time and money that researchers couldn’t justify.

A basket trial, however, capitalizes on the growing understanding that cancers should be characterized by not just where they start (in the breast, colon or lung, for example) but also by how they grow — which mutations are driving them. A basket trial collects patients, all of whom have BRAF mutations, for instance, but who might have different types of cancer.

In the NEJM study, patients with non small cell lung cancer, colon cancer, thyroid cancer, multiple myeloma and, glioblastomas, among others, were included. By studying them as a group, Hyman says it’s possible to get a better idea of how feasible it is to target mutations like BRAF among those who don’t have melanoma.

So far, the results are encouraging. Patients with non small cell lung cancer seemed to have the best response rate to vemurafenib, 42%, after a year. More than 70% of the patients with this cancer saw their tumors shrink by at least 30% in length. There were promising signs that patients with the other, untreatable cancers also responded and took longer before their tumors progressed than they would have without the experimental therapy.

Anselmo was among the extraordinary responders. “It is unusual,” says Hyman of the apparent shrinkage of her tumor. “She really is an outlier in any way you measure it.”

NEJM 373; 8; 2015. Courtesy Dr. David Hyman: Anselmo’s brain tumor at the start of the study in 2014 (left) and on Aug. 11, 2015 (right)

But it’s precisely for patients like Anselmo that basket trials are being considered — the possibility that there may be one, two or however many patients who, rather than facing a poor prognosis with existing or non-existent options for treating their disease, may have a chance, however small, of living longer and even controlling their cancer.

“One of the things that gets lost when we talk averages and medians is how many patients benefit and for how long,” says Hyman. “There is a tremendous range and a concern that promoting the best successes sets the bar very high. But it also lets people know that things are not entirely hopeless, that there are people who have tremendous benefit from therapies and not get completely caught up in medians and averages.”

That being said, Hyman cautions that more work needs to be done to better apply the principles of precision medicine to improve patients’ outcomes. Since most tumors have many mutations, how can doctors determine which one, or ones, to target with drugs? Why do some patients respond very well, while others do not?

Another looming question has to do with how cancer doctors can start to incorporate what they are learning about mutations and cancer-causing pathways with their more traditional knowledge based on where tumors start. In the study, for example, patients with BRAF colon cancers did not respond to vemurafenib; but some started to show responses when vemurafenib was combined with another drug, cetuximab. That suggests that knowing where the cancer originates may still be an important part of the puzzle in figuring out which treatments might work best for which types of cancers.

In an editorial accompanying the study, researchers at the T.H. Chan Harvard School of Public Health and Boston University note that basket trials may be just the first step in a precision medicine approach to cancer. Once doctors figure out which types of cancers might respond best to, for example, a BRAF-focused drug, they might conduct additional trials on each of these cancers to determine which patients, like Anselmo, would benefit most.

For her, the trail has provided the chance to sing again. A jazz vocalist, she performed at a friend’s birthday party and attended a song-writing retreat in upstate New York. She makes weekly visits to her doctors — to the dermatologist to monitor any side effects from the drug, to Hyman every two months for a brain scan, and to get lab tests done to check on her immune system. And she’s tired all the time. “But that’s par for the course,” she says. “I’m just lucky to be alive at a time when cancer care is so different than it was years ago. Who would have known that treatments could be so customized? It’s so amazing, and I’m very thankful to be a part of it.”


TIME Cancer

The Connection Between Light Drinking and Cancer: Study

healthiest foods, health food, diet, nutrition, time.com stock, red wine, alcohol
Danny Kim for TIME

The latest study shows how much alcohol is linked to a higher risk of developing certain cancers

Researchers say that indulging in as little as one drink a day for women and two drinks daily for men can boost the risk of breast, colon, oral, liver and esophageal cancers. But the risk was higher for men who smoked, even those who had quit, than for non smokers.

Scientists at the Harvard T. H. Chan School of Public Health and Brigham and Women’s Hospital report in the BMJ on a review of nearly 136,000 men and women enrolled in studies that followed their health-related behaviors and outcomes for 30 years. Overall, those who drank more showed a higher risk of alcohol-related cancers, which wasn’t surprising, given that over-indulging can promote abnormal growths in certain organs like the liver.

MORE: 5 Things You Need to Know About Alcohol, Backed By Research

But what was more surprising was that, according to their observations, it didn’t take much. Previous studies have focused on heavy drinking, while the current analysis looked at light to moderate drinking. Among women, up to one drink a day contributed to a 13% higher risk of developing alcohol-related cancers, primarily breast cancer. For men, up to two drinks a day also increased the risk of certain cancers, but only for those who had smoked. Non smoking men didn’t show any higher risk.

The results suggest that smoking may be an important contributor to certain cancers, especially in combination with alcohol. In fact, says Yin Cao, a post doctoral research fellow at the School of Public Health and lead author of the study, it’s enough to consider becoming even stricter when it comes to imbibing. “For men, especially those who ever smoked, they should limit alcohol to even below the recommended limit,” she says. “And smoking and heavy alcohol consumption should be absolutely avoided to prevent cancer.”



TIME Jimmy Carter

Jimmy Carter Diagnosed With Cancer

Carter was the 39th President of the United States.

Former President Jimmy Carter just revealed that he has been diagnosed with cancer.

He posted a statement about the diagnosis on the website of The Carter Center on Wednesday.

“Recent liver surgery revealed that I have cancer that now is in other parts of my body. I will be rearranging my schedule as necessary so I can undergo treatment by physicians at Emory Healthcare,” Carter wrote. “A more complete public statement will be made when facts are known, possibly next week.”

Among other well-wishers, President Barack Obama called Carter to wish him a full recovery, the White House said. Vice President Joe Biden also spoke with Carter.

Carter, 90, was the 39th President of the United States.

TIME Diet/Nutrition

Should I Eat Hot Dogs?

4/5 experts say no.

Ballgame or no ballgame, hot dogs aren’t hot in the health world, according to four of our experts.

Hot dogs deliver a nutritional assault in many ways: one typical fast food dog with ketchup and mustard contains 290 calories and 910 mg of sodium. (On the plus side, you’re also getting 11 grams of protein.)

The problem with hot dogs is how they’re processed. “While there is some debate about the health effects of pure meats, processed meats—and all hot dogs fall into that category, some more processed than others—are consistently associated with adverse health effects,” says Dr. David Katz, director of the Yale University Prevention Research Center. Diets high in processed meats have been linked with cancer, especially colorectal cancer.

Peter Clifton, professor of nutrition at the University of South Australia, puts it this way: “All data says processed meat is bad: more diabetes, higher mortality, more cardiovascular disease,” he says. His March paper published in the journal Metabolism found that processed foods are associated with an increased risk for type 2 diabetes compared to red meat, probably partly due to the way that iron interacts with the saturated fat, salt and nitrates—an added preservative—found in processed meats.

Nitrates are of particular concern with cured meats like hot dogs, says Mariana Stern, a cancer epidemiologist at the University of Southern California. Nitrates are salts added from synthetic chemicals or natural sources (such as celery juice, which you may find on the labels of so-called “uncured” or “nitrate-free” hot dogs). “Regardless of where the nitrates come from,” says Stern, “they can be converted by oral bacteria intro nitrites, which in turn can react in the stomach … to form N-Nitroso compounds, which are well-established cancer-causing agents.”

Antioxidants can halt this conversion, which is why most hot dogs contain vitamin C, Stern says. “However, the amounts in one hot dog may not be enough to prevent the accumulation of N-Nitroso compounds in people with diets high in meat overall, and in particular processed meats,” she says. “Studies show that the effects of processed meats might be more harmful in people with diets that are overall low in antioxidants.” Stern analyzed the diets of 1,660 people with bladder cancer and found that bladder cancer risk went up with processed meat consumption.

In an April study looking at the effects of nitrites in mice, “we have shown that addition of nitrite had a neutral, and maybe even protective effect on intestinal tumor development when part of a low-fat diet,” says Marianne Sødring, a PhD student at the Department of Food Safety and Infection Biology at Norwegian University of Life Sciences. “This may suggest that other factors have to be present for nitrite-processed meat to have a cancer-causing effect.”

There might be an easier way to lower the risks associated with processed meat—if you’re a rat, at least. Scientists, reporting their findings in the International Journal of Cancer, fed rats hot dogs and watched a particular biomarker for colorectal cancer; the hot dog diet indeed increased signs of this marker, but adding calcium to their diet lessened this effect. “If a rat’s diet is loaded with calcium, a hotdog diet does not boost cancer anymore in rats,” says study author Denis Corpet, professor of food hygiene and human nutrition in the French National School of Veterinary Medicine in Toulouse. “In people, this would translate in having a yogurt each time we get a pair of sausages.”

If you want to indulge in the occasional dog (plus or minus the yogurt), Sødring—the lone hot dog defender—has some parting words of encouragement. “As a bonus, from an environmental standpoint, one might say that hot dogs contribute to sustainable food production,” she says, “because a much larger part of the animal, not just the prime cuts, is utilized.”

hot dog
Illustration by Lon Tweeten for TIME

Read Next: Should I Eat Pretzels?

TIME Innovation

Why New Orleans Bounced Back

The Aspen Institute is an educational and policy studies organization based in Washington, D.C.

These are today's best ideas

1. A decade after Hurricane Katrina, New Orleans has harnessed the “edgy creativity that comes from the shared aftertaste of danger.”

By Walter Isaacson in the New York Times

2. Could a tumor send real-time progress reports on cancer treatment?

By Chris Berdick in MIT News

3. Where should we start fighting campus sexual assault? Let’s try high school.

By Tyler Kingkade and Rebecca Klein in the Huffington Post

4. To expedite innovation, give away your code.

By Gus Robertson in TechCrunch

5. Simply defending against hackers isn’t working. Maybe U.S. businesses should go on offense.

By Grant Gross in IT World

The Aspen Institute is an educational and policy studies organization based in Washington, D.C.

TIME Ideas hosts the world's leading voices, providing commentary and expertise on the most compelling events in news, society, and culture. We welcome outside contributions. To submit a piece, email ideas@time.com.

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