Cracking Cancer's Secret Code: Oncologist Searches for Breast Cancer’s Achilles’ Heel

Triple-negative breast cancer has been defined by what it is not, but Dr. Jennifer Pietenpol and her team has identified six different subtypes of the disease.

Over the last decade, oncologist Jennifer Pietenpol has been trying to decode and kill a difficult-to-treat type of breast cancer. Known as triple-negative breast cancer, this form of the disease can be highly aggressive and resistant to chemotherapy.

The cancer, which accounts for 10 to 20 percent of all breast cancers in the United States, is also a deadly genetic riddle that doctors find easiest to describe in terms of what it is not. “Between 75 to 85 percent of breast cancers express one of three clear targets for therapy,” says Pietenpol, who runs the Vanderbilt-Ingram Cancer Center in Nashville, Tenn. “But with triple-negative cancer, there is nothing to attack and patients go into a standard of care that involves combinations of chemotherapy that have been determined by experiment. We felt that in this era of precision medicine, we should get a better handle on the treatment.”

Pietenpol and her team have collected and analyzed more than 600 cases of triple-negative breast cancer so far, and their results have defined six biological subtypes of the disease. This breakthrough could help scientists apply existing drugs and procedures to attack the cancer, develop new ones, and map out treatment.



Last year, GE’s Healthymagination Challenge, an open innovation quest that seeks to find and fund the best new ideas in breast cancer detection and treatment, gave Pietenpol’s team $100,000 to finance more science. “We are beginning to get that molecular information from an individual patient’s tumor,” she says. “This is helping us guide therapy and align it with patients. Every bit of additional funding helps to accelerate this further.”

Doctors divide breast cancer into four groups, based on what is driving tumor growth. The vast majority of breast cancers use the estrogen receptor, the progesterone receptor or the HER2 pathway for growth. “When we see this, we can apply existing therapy, like Tamoxifen,” Pietenpol says.

Her research group and other teams are now looking for similar tools and targets to destroy the fourth type of breast cancer, triple-negative cancer. “Our task is to understand how these tumor cells grow, find their Achilles’ heel, and how we can hit it,” she says.

Pietenpol starts by looking at the different pathways the tumor cells appear to use to signal growth, pairs that information with genetic data about how the cells mutate and then tests the hypotheses in her lab. “In cancer, we want to move to predictive oncology where we can use molecular information to better guide treatment,” she says.

Pietenpol’s team has already pinned six unique targets to triple-negative cancer’s back. One of them, an androgen receptor, could expose as many as 10 percent of triple-negative cancer cases to attack. But additional targets will likely be smaller. “As we go more into precision medicine, the fraction of people with any given molecular subtype will get smaller and smaller,” she says. “This is where we are going, using much more precision therapy where no two tumors are going to be alike.”

Pietenpol’s team has started designing clinical trials for each of the six subtypes. She says that “androgen-receptor antagonists” used for treating prostate cancer could be effective against the androgen receptor subset her team discovered. “We are continuing to accelerate this, but we have a lot of work to do,” she says. “We’ve just begun to uncover these lower hanging fruits.”

DIY Cancer Test: Cancer Scare Pushed GE Physicist to Develop Her Own Screening Method

It was a moment that many of us fear. A few years ago Ileana Hancu went for a routine physical exam and came back with troubling news. Her doctor thought that she felt a lump in her breast. What followed was an odyssey through the achievements of modern medicine, from mammography, to ultrasound and near biopsy. “But then the biopsy doctor decided that he could not see anything that he could biopsy,” Hancu says. She went for yet another test, an MRI exam, which gave her doctor enough information to conclude that no further screening was necessary. “In my case it was nothing, it was just a scare that took a month,” Hancu says. “But it made me realize that the way things are right now, even though we have so many imaging tools, we are not as good as we could be.”

Hancu, who is a physicist by training and MRI researcher at GE Global Research (GRC), couldn’t let her experience go. She went into her lab and designed an imaging solution that could one day save women like her from a similar ordeal. “I want the doctor to be able to look at all the images from an examination, and know for sure that everything is all right, or whether there is cancer,” she says. "Nobody needs or wants uncertainty at the end of a test."

Quality Control: “I measure success by making an impact on somebody’s life,” says Ileana Hancu.

Hancu’s research could be a boon for women in groups for whom mammograms can often be inconclusive, such as those with dense breasts. Her goal is to help eliminate the uncertainties when this group is screened. “You want to find out the answer about the positive or negative at that moment in time,” she says.

Hancu grew up in Bucharest, Romania, in a scientific family. Her father was a computer programmer, her mother was chemist, and Hancu enrolled at the university to study optics. “There probably wasn’t a single MRI machine in the whole country at that point in time,” she laughs. After graduation in 1996, she moved to study physics the University of Pittsburgh and discovered magnetic resonance. A few years later, she had a doctorate in the esoteric field. “That’s why I ended up at the GRC,” she says. “There are few places in the world that could use that kind of expertise.”

Hancu was in the middle of MRI research when her cancer scare struck. MRI had been used in the clinic for breast cancer diagnosis, but standard MRI images produced too many false positives, or lesions, which turned out to be benign at biopsy.

A new MRI-based method meant to clarify the picture, called diffusion-weighted imaging, has “bounced around the literature for the past few years,” Hancu says. “But the diffusion-weighted images were kind of lousy,” she says. They were like a screenshot from a TV with a bad antenna, fuzzy and distorted. A doctor could not truly read them and use them to decide the fate of a patient.

Hancu has started experimenting with methods that would increase the MRI signal and the spatial resolution of the images so that she could see even smaller tumors. One of her approaches involves building the MRI equivalent of a high-resolution camera.

The research work has already earned Hancu and her collaborator, Prof. Robert Lenkinski from the University of Texas Southwestern Medical Center, a five-year, $3.2 million grant from the National Institutes of Health. They plan to test their technology on patients in a clinical trial to help further evaluate its use in breast cancer diagnosis.

Hancu says that learning is not an academic exercise for her. “If you end up developing an imaging technique that will help save people from having biopsies, if you can develop a technique that can tell you with certitude whether you have cancer or not, I think that’s the final measure of success,” Hancu says.

“I measure success by making an impact on somebody’s life.”

Family Matters: GE Technology Helps Healthcare Providers in Africa

The rural health clinic in Kimalamisale, Tanzania, sits at the end of a rutted sandy road some 160 miles from the nearest large town of Kisarawe. Although the brightly colored concrete structure serves thousands of villagers living in the surrounding savannah, it has no electricity and its main healthcare equipment includes a stethoscope, weighing scales, and a blood pressure machine.

Things changed last spring, when a trained nurse arrived with Vscan, a pocket-size ultrasound machine manufactured by GE. Her visit was part of a research study designed to test technological innovations that will help speed up governmental efforts to meet Millennium Development Goals 4 and 5 in Africa. The study was developed by Tanzania’s Ifakara Health Institute in partnership with GE’s healthymagination campaign.

In Tanzania, hemorrhage, obstructed labor, sepsis and other pregnancy complications cause 454 maternal deaths per 100,000 live births. That’s more than three times above a U.N. Millennium Development Goal of 133 deaths by 2015.

Women in rural Tanzania first showed no emotional reaction to ultrasound images of their babies on VScan. They thought that nurses uploaded the pictures beforehand.

Ifakara trained a total of 14 nurse midwives in ultrasound scanning. They fanned out across the Kisarawe district, population 230,000 of which 28 percent are women of reproductive age, to five rural clinics like the one in Kimalamisale, a health center, and a district hospital. “Newborn and maternal health is the most critical health issue in Africa, ahead of malaria or AIDS,” says Janeen Uzzell, Director of Healthcare Programs for healthymagination in Africa. “We want to show that GE is committed to the lives of mothers and babies in Africa.”

Similar studies had been done in rural Bangladesh and Indonesia, but Africa presented additional challenges. The rural clinics in Tanzania rely on solar panels for electricity, lack telephone service, and suffer from bad roads and no ambulances. But using a process called “reverse innovation,” the team was able to power Vscan by solar panels and let professionals use in the village after just 10 days of training. “In Africa, what the product actually enables is what matters the most,” says Uzzell.

The program used local doctors to train nurses who had not used ultrasound before. It includes rigorous quality control “to make sure that the nurses are doing what we want them to do,” says Kallol Mukherji, GE Program Manager in Tanzania.

Mukherji, who helped run similar projects in Asia, says that he was initially surprised when the women in Tanzania showed no emotional reaction to the images on the ultrasound screen. “They thought that we uploaded the picture beforehand,” he says. “They did not believe that you could actually see your baby before it’s born through a device.”

That may soon change. The Vscan is already helping healthcare professionals in Ethiopia, and Ghana recently signed an order to purchase 400 of the machines. Uzzell is now working with Nigeria’s Ministry of Health’s Saving One Million Lives initiative to reduce neonatal mortality in the country’s northern region. “We don’t just have a product,” Uzzell says. “We have a visualization tool that can help change maternal and newborn health in Africa.”

When Saving Lives is Contagious: Can Successful Treatments Spread From One Hospital to Others? GE is Working on Finding Out

Making people healthier does not always involve developing a more potent pill or building a better body imaging machine. Sometimes it pays to keep your eyes open and listen. A few years ago a group of care delivery professionals from GE Healthcare noticed that some hospitals were getting much better results than others. “Their ideas were new and innovative, but they were also incremental and did not turn the facility upside down,” says Denise Kruzikas, a healthymagination director at GE Healthcare. “They made care smoother, faster, and more efficient.”



What were these hospitals doing right and could it serve as a “best practice” for others? “We started looking for the true pioneers,” Kruzikas says. GE’s first visit was to Saint Luke’s Neuroscience Institute in Kansas City, Missouri, a leading stroke treatment center. Doctors at Saint Luke’s, a long-time GE customer, were using GE imaging technology to diagnose stroke patients. They were getting better results than others and the GE team wanted to know why.

Typically, no more than 5 percent of stroke patients receive “interventional treatment,” where doctors remove the blood clot in the brain that blocked an artery. This is because patients were not diagnosed properly or did not arrive at the hospital in time. However, Saint Luke’s developed an innovative stroke treatment protocol and increased this number to 40 percent, say Dr. Marilyn Rymer, medical director at the Neuroscience Institute. When stroke patients leave her hospital, they are doing better, have lower stroke severity scores, and stand a better chance to resume their lives. “Saint Luke’s combines education, outreach, and coordination with efficient care,” Kruzikas says. “They’ve got people, process and technology working together.”

Starting in 2005, Dr. Rymer’s team turned stroke treatment at the hospital into a series of interconnected steps, each with a measurable outcome. The steps ranged from teaching regional hospitals and EMT personnel to recognize stroke, performing a CT scan on suspected stroke patients to help inform treatment, and also starting physical, occupational and speech therapy a lot sooner to speed up the recovery and the quality of life. “It is critical for us to be as fast as we can at all times,” says Bridget Brion, a “Code Neuro” nurse at Saint Luke’s intensive care unit. “Every minute of a stroke one million brain cells die.” “Code Neuro” ICU nurses like Brion work directly with emergency room staff to care for a stroke patient. “Instead of having the emergency room acting as an independent silo taking care of stroke, we have a continuity of care that starts immediately when a stroke patient arrives until they go home,” Dr. Rymer says.

The GE team came in 2009 and took a “full download” of Saint Luke’s stroke data since the beginning of the new program. The researchers looked at patient volumes and outcomes, stroke education, time to diagnosis and treatment, length of stay, and costs.

The analysis showed that between 2005 and 2010, the hospital increased the amount of stroke patients by 23 percent and boosted transfers by 17 percent. Around 40 percent of stroke patients at Saint Luke’s receive interventional stroke treatment such as clot-dissolving medication deployed directly at the site of a blood clot in the brain. The average across the healthcare system is only 3 to 5 percent. Given the important stroke related information it provides in a relatively short time, nearly all stroke patients at Saint Luke’s receive a CT scan followed by specialized post-processing analysis. “The bottom line was that patients were doing better and they were able to get discharged earlier,” Kruzikas says.

Last June, Dr. Rymer traveled to GE’s training and education center in Crotonville, New York, and presented the results as “best practice” steps to stroke doctors from the U.S. and abroad. “Every hospital around the country should be stroke ready and stroke able,” Dr. Rymer says. “That just hasn’t happened.” Stroke is the leading cause of disability among adults in the U.S. Approximately 795,000 strokes occur in the U.S., costing $25 billion in 2007.

The Saint Luke’s study was part of GE’s healthymagination program, whose goals include finding innovative solutions to healthcare and improving access to treatment. The GE team is already seeking out facilities that excel in treating breast cancer, Alzheimer’s disease, and low-dose radiation management. “It’s about using what’s out there in a more efficient and productive way,” Kruzikas says. “We want to address our customer’s need and support best practice models that can be replicated around the world.”

Saving Tiny Lives with help from LED Lights and Warm Beds

Dr. Rajesh Kumar and his team of 20 pediatricians inside Rani Children’s Hospital in the impoverished Indian state of Jharkhand are facing a daunting task. Dr. Kumar is one of the few neonatologists serving Jharkhand, population 32 million. On a typical day, he and his team scramble to care for as many as 100 newborns, some weighing less than two pounds at birth. Technology is a matter of life and death for Dr. Kumar’s tiny patients, and it had been slow to reach them.

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Until last fall, when Rani Children’s Hospital’s neonatal intensive care unit installed first Lullaby baby warmers and phototherapy units from GE. GE built the machines specifically for the Indian market, using a process called “reverse innovation.” Vijay Govindarajan, professor at Dartmouth’s Tuck School of Business and author of Reverse Innovation: Create Far from Home, Win Everywhere, says that smart companies innovate in developing markets, meet local needs and constraints, and then bring the results home. “Once you do that, your solutions become very novel,” he says.



The baby warmer’s easy controls, pictogram buttons, and simple dials, for example, are intuitive and give nurses and doctors more time to focus on the baby, not switches. Hospitals in 65 countries, including some from Western Europe, have placed orders.

Speaking on his cell phone one busy Monday morning from the hospital, Dr. Kumar said that he was managing 50 babies using the Lullaby warmers. “They cannot maintain their own body temperature,” he explained. His staff have been using the warmers in combination with GE's LED phototherapy system. The system is very efficient in treating infants with neonatal jaundice, a common illness caused by an immature liver. If left untreated, bilirubin, the yellow byproduct of dying blood cells, can build up in the body and cause irreversible brain damage. Phototherapy helps transform the bilirubin into a new compound that the baby can excrete. “Technologies like low cost baby warmers and LED phototherapy systems can help save many newborn lives every day, especially in a country like India,” said Dr. Kumar.

The LEDs in the Lullaby last 50,000 hours, almost six years, compared to 1,000 or 2,000 hours for standard fluorescent lamps that require replacement every 3 months and use five times as much energy. The infants depend on the lights to get better, or they must receive a blood transfusion. Lullaby phototherapy devices at Rani Children’s Hospital use LEDs that were developed in India to specifically replace the high-intensity bulbs.

Last month the Lullaby LED phototherapy system won an innovation award from the Federation of Indian Chambers of Commerce and Industry (FICCI), ahead of 120 other new entrants in the field of low cost sustainable innovations that help enable better healthcare for more people.

Says Dartmouth’s Govindarajan: “Every GE employee must have a reverse innovation mindset. It’s the biggest opportunity for GE going forward.”

Pretty on the Inside: New BodyMaps App Lets Users Explore the Inside of the Body

Some of earliest and best anatomical drawings come from Leonardo da Vinci. The renaissance polymath would sit in on human and animal autopsies (he would sometimes cut the bodies himself) and record his observations in detailed drawings fringed with copious notes. He also made realistic body part models by injecting molten wax inside the cranium and the aortic valve and studied their shape and function. His work, however, progressed in fits and starts. Leonardo was hamstrung by the lack of cadavers (often the bodies of criminals) and a ban on human dissections issued by the Pope. His drawings remained out of sight for 400 years after his death in 1519, despite their revolutionary nature.

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Body Check: The BodyMaps app allows users see inside and learn about the body. Doctors can use it to explain medical procedures.
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The app, which was specifically developed for the iPad’s Retina display, features anatomy models of both sexes.
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BodyMaps features 3D, high-resolution images of more than 1,000 body parts, tissues, bones and organs, all captured in a searchable index.
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BodyMaps features 3D, high-resolution images of more than 1,000 body parts, tissues, bones and organs, all captured in a searchable index.
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Doctors and nurses can draw directly on the images and highlight information for patients.
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There is no need to worry about Papal wrath or corpse supply in the digital era. Anybody, from medical students and professionals to enthusiasts and artists, can view the inside of the human body in sharp detail with a new app called BodyMaps and launched today by GE and Healthline Networks. The app, which was specifically developed for the iPad’s Retina display, features 3D, high-resolution images of more than 1,000 body parts, tissues, bones and organs, all captured in a searchable index. Just like Leonardo’s multi-view models, users can rotate more than 30 body parts for a better look. They can also toggle between the male and female body.

BodyMaps also contains 200 videos covering various medical conditions, procedures, and treatments, as well as a mark-up tool. Doctors and nurses can draw directly on the images and highlight information for patients. The app is social media ready and users can share their mark-ups and notes through email and Facebook.

“For patients, the [visual] resources were very scarce all through the medical world,” says Gloria Horns, a nurse educator and well-known patient advocate at University of California, San Francisco. “You were creating your own, reinventing the wheel every time, and working with diagrams, charts, and flat images.”

Horns has cared for many organ transplant patients during her long career. She says that the new app “is really going to be a terrific tool for the nurses that are teaching these patients through the whole course of the illness.”

Says Horns: “They are really going to get it. It’s hard to describe how this will help us. It’s pretty phenomenal.”

Fantastic Voyage: GE Invests in Bowel Surfing Capsule that May Help Doctors Detect Colon Cancer

There are better ways to pass time than prepping for a colonoscopy. This week, the GE healthymagination fund invested in Israeli company called Check-Cap Ltd. seeking to change that experience.

Inside knowledge: Check-Cap’s capsule may help doctors screen for polyps, the precursors of colorectal cancer.

Check-Cap designed an ingestible capsule that snaps pictures as it travels through the bowels. The device, which employs low energy X-ray-based technology to safely generate high resolution 3D imagery, may help doctors detect colorectal cancer. No cleansing involved. The capsule continuously transmits information to a wrist-worn data receiver. Patients can go play a round of golf or take a walk while the tiny device does its work. At the end of the journey, the capsule leaves the body the “natural” way.

The $250 million healthymagination fund invests in promising healthcare technology companies. It has focused on diagnostics, medical information management technology, and life sciences.

GE Healthcare and Check-Cap will also design and manufacture miniature cadmium zinc telluride (CZT) diagnostic imaging sensors placed inside each Check-Cap capsule. The sensors will give clinicians a full 360-degree view as the capsule moves through the colon. GE Healthcare has many years of experience in developing CZT-based detectors. Similar technologies have been used in the company’s nuclear medicine and bone densitometry systems.

Intrepid traveler: As it moves through the colon, the device transmits data to a wrist-worn receiver. No bowel cleansing required.

Colorectal cancer is the third most common cancer in men and the second in women, according to the International Agency for Research on Cancer. Almost 60 percent of the cases occur in developed regions. Globally, it is the fourth most common cause of death from cancer. About 608,000 deaths from colorectal cancer are estimated worldwide annually, accounting for 8 percent of all cancer deaths. In the United States, colorectal cancer is the second leading cause of death from cancer.

Check-Cap plans to introduce its capsule in the European Union in late 2013, subject to regulatory approval. The company is also in discussions with the U. S. Food & Drug Administration (FDA).