National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
April 19, 2011 • Volume 8 / Number 8

NEWS

Active Surveillance May Be Preferred Option in Some Men with Prostate Cancer

A doctor talking with male patient

Findings of a recent study, the largest and longest of its kind, provide strong evidence supporting a conservative approach to managing prostate cancer in some men. The study was not a randomized clinical trial; rather, it was a long-term analysis of a cohort of men diagnosed with what is called very-low-risk prostate cancer. Instead of immediately undergoing surgery or radiation therapy, the men had opted to undergo a process known as active surveillance at the Johns Hopkins University School of Medicine.

A diagnosis of very-low-risk prostate cancer means that the disease is highly unlikely to become a clinically significant, life-threatening cancer. These men could be safely monitored by active surveillance, the study found, with only a modest percentage eventually requiring some form of treatment and none dying from prostate cancer. Read more > >

COMMENTARY

Inside NCI: A Conversation with Dr. Lauren Wood about Cancer Vaccines and Health Disparities Article contains video


A senior clinical investigator in NCI’s Vaccine Branch discusses the most recent advances in immune-based therapies and how clinical trials are important to the work she does. She also highlights why Minority Cancer Awareness Week is important and why barriers to clinical trials participation among minority populations still exist.  Read more > >
  

IN DEPTH

UPDATES

  • FDA Updates

    • FDA Approves New Treatment for Medullary Thyroid Cancer
    • Advisory Panel Recommends Targeted Therapies for Treating Rare Pancreatic Tumors
    • FDA Initiates Safety Review of Myeloma Drug for Possible Cancer Risk
  • Cancer.gov Update

    • NCI Recovery Act Web Site Highlights Small Businesses Driving Innovation in Cancer Care
  • Notes

    • NCI Cancer Classroom Webinar Series Kicks Off April 26
    • Breast Cancer Guidelines Proposed for Low- and Middle-Income Countries
    • Two-Year Project Launched to Standardize Cytogenetic Testing in Mexico
    • “Stupid Cancer Show” to Host Program on Clinical Trials Myths

Selected articles from past issues of the NCI Cancer Bulletin are available in Spanish.

The NCI Cancer Bulletin is produced by the National Cancer Institute (NCI), which was established in 1937. Through basic, clinical, and population-based biomedical research and training, NCI conducts and supports research that will lead to a future in which we can identify the environmental and genetic causes of cancer, prevent cancer before it starts, identify cancers that do develop at the earliest stage, eliminate cancers through innovative treatment interventions, and biologically control those cancers that we cannot eliminate so they become manageable, chronic diseases.

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Featured Article

Active Surveillance May Be Preferred Option in Some Men with Prostate Cancer

A doctor talking with male patientA diagnosis of very-low-risk prostate cancer means it is highly unlikely to become a clinically significant, life-threatening cancer.

Findings of a recent study, the largest and longest of its kind, provide strong evidence supporting a conservative approach to managing prostate cancer in some men. The study was not a randomized clinical trial; rather, it was a long-term analysis of a cohort of men diagnosed with what is called very-low-risk prostate cancer. Instead of immediately undergoing surgery or radiation therapy, the men had opted to undergo a process known as active surveillance at the Johns Hopkins University School of Medicine.

A diagnosis of very-low-risk prostate cancer means that the disease is highly unlikely to become a clinically significant, life-threatening cancer. These men could be safely monitored by active surveillance, the study found, with only a modest percentage eventually requiring some form of treatment and none dying from prostate cancer. The results were published online April 4 in the Journal of Clinical Oncology (JCO).

As is the case with prostate cancer in general in the United States, most of the men in the study were 65 or older. The results provide very strong evidence that active surveillance is the “preferred option” for most men in this age group with very-low-risk disease, said the study’s senior investigator, Dr. H. Ballentine Carter. In fact, he continued, “The overwhelming evidence says that for men over 65 who are diagnosed with low-risk disease, their first question should be whether any therapy is appropriate for them, not which therapy.”

The clinical relevance of the findings is hard to overstate, Dr. Carter stressed. Among the 217,000 men in the United States diagnosed each year with prostate cancer, a substantial proportion has very-low-risk or low-risk disease. The vast majority of these men immediately undergo some form of treatment, including men aged 75 and over, despite the fact that many would be unlikely to experience significant symptoms, let alone die from prostate cancer.

Defining Very-Low-Risk Prostate Cancer

The Johns Hopkins definition of very-low-risk prostate cancer is similar to the NCCN definition. For the study in JCO, very-low-risk was defined as:

  • Clinical stage T1c (no palpable disease, biopsy recommended based on abnormal PSA)
  • Gleason score of 6 or less
  • PSA density (ratio of PSA level to prostate gland size) of 0.15 ng/mL or less
  • Two or fewer biopsy cores in which cancer is present, and less than 50 percent cancer present in any involved core

Patient Selection, Compliance Are Key

At Hopkins, the active surveillance program involves a semi-annual check-up and an annual biopsy. Patient selection is very important, Dr. Carter explained.

Among the 769 men enrolled in Hopkins’ active surveillance program between 1995 and 2010, approximately 80 percent had very-low-risk disease. Whether a patient has very-low-risk disease is determined based on factors such as the Gleason score (a common measure of tumor aggressiveness) and the extent of cancer in the biopsy samples, or cores, from the prostate gland. (See the sidebar for all of the factors.)

The remaining men had at least one biopsy feature that precluded their disease from being considered very-low-risk, Dr. Carter explained. These men were typically older and had other health problems, he continued, which made active surveillance more attractive than treatment with surgery or radiation, both of which can have significant side effects.

Compliance with the approach has been quite strong, the Hopkins team reported, with nearly 90 percent of participants completing their annual biopsies.

Although no men in the study died of prostate cancer, 255 did undergo some form of treatment, 74 percent of whom did so because their disease was reclassified based on the findings of an annual biopsy.

Overall, 41 percent of men in the study did not require any form of treatment, even after 10 years of follow-up, a “remarkable” finding, said Dr. Bhupinder Mann from NCI’s Division of Cancer Treatment and Diagnosis. “This study adds to the accumulating evidence that, in carefully selected patients, active surveillance is safe.”

The results “strongly support” recent revisions to prostate cancer treatment guidelines from the National Comprehensive Cancer Network (NCCN), said the guidelines’ panel chair, Dr. James Mohler from the Roswell Park Cancer Institute. Updated last year, the guidelines recommend that physicians advise men with very-low-risk disease who have a life expectancy of up to 20 years to pursue active surveillance.

Findings like these on active surveillance, combined with related research on the growing problem of overdiagnosis and overtreatment of prostate cancer linked to PSA screening, appear to be reaching down into the community setting, Dr. Mohler believes.

“I think men and their doctors are becoming more educated about the overtreatment issue,” he said.

As evidence, Dr. Mohler pointed to the START trial, a phase III clinical trial being led by NCI-Canada, in collaboration with the U.S. NCI, in which men diagnosed with very-low-risk or low-risk disease are being randomly assigned to active surveillance or immediate treatment. When the trial opened in 2007, most men who declined to enroll did so because they did not want to take the risk of being assigned to the active surveillance arm. “Now most men are declining to participate because they want active surveillance,” Dr. Mohler said.

Having a strong system in place to ensure that men pursuing active surveillance are followed and receive reminders for their check-ups and biopsies is extremely important, Dr. Carter stressed.

At the moment, the Hopkins surveillance program is managed primarily by an administrator using a manual process. But the program is moving to a Web-based approach for monitoring and following patients, he added.

Approaches Can Vary

Although the evidence in favor of active surveillance continues to accumulate, the optimal approach to managing the process is not yet defined, Dr. Mann noted. This is particularly true with respect to how patients’ disease is tracked.

At Hopkins, men are followed via check-ups and annual biopsies. Any reclassification of their disease is typically based on biopsy findings, such as a change in Gleason score, which might then produce a recommendation for treatment. But many other centers, such as Roswell Park, do not require men who choose active surveillance to undergo regular biopsies. Rather, they use some form of what is commonly called PSA kinetics, which are changes in PSA levels over time (for instance, how long it takes for PSA levels to double).

Results from several studies, however, have raised doubts about the value of PSA kinetics in initially identifying or managing prostate cancer. Based on their experience, PSA kinetics is “not reliable for predicting the presence of high-grade cancer on an individual basis,” the Hopkins team wrote in JCO. “Thus, if the goal of surveillance is to identify and treat higher-risk cancers, we believe that annual biopsies may be necessary to ensure patient safety.”

But regular biopsies are by no means without their own risks. A small percentage of men end up in the hospital with antibiotic resistant infections as a result of a prostate biopsy, Dr. Mohler said, and repeat biopsies can lead to inflammation and scar tissue formation that can preclude nerve-sparing surgery to treat the prostate cancer in some men whose disease progresses.

According to Dr. Carter, Hopkins researchers are now studying whether men who have had two consecutive biopsies that show no evidence of disease progression can safely have the interval between routine biopsies extended. In the meantime, the NCCN guidelines are being revised again, Dr. Mohler said, using data from large active surveillance programs at Hopkins, the University of Toronto, and the University of California, San Francisco, to provide recommendations on managing men who choose this conservative approach.

Further clarity on this matter should be forthcoming, Dr. Mann said. In addition to the START trial, which will follow men using both PSA measures and prostate core biopsies, a similar trial is being conducted in the United Kingdom that is using only PSA levels to monitor patients. Also, in December, NCI and CDC are sponsoring an NIH State-of-the-Science Conference to review the role of active surveillance in managing localized prostate cancer and to help guide future research in this area. 

Carmen Phillips

Cancer Research Highlights

Cancer Burden among People Infected with HIV Changing in U.S.

The number of cancers not traditionally associated with AIDS rose sharply between 1991 and 2005 among people living with HIV. Among contributing factors, the introduction of highly active antiretroviral therapy (HAART) in the mid-1990s greatly prolonged survival for people living with HIV. As more of these people reach ages at which cancer risk increases, the number of these cancers is likely to continue to rise, Dr. Meredith Shiels of NCI’s Division of Cancer Epidemiology and Genetics (DCEG) and her colleagues reported online in the Journal of the National Cancer Institute on April 11.

The researchers collected data from the ongoing HIV/AIDS Cancer Match Study, which links 15 U.S. cancer registries and HIV registries, and from the Centers for Disease Control and Prevention (CDC) AIDS registries, which monitor the number of people living with AIDS in all 50 states.

The researchers found that though the number of people living with AIDS rose from 96,179 in 1991 to 413,080 in 2005, the estimated number of “AIDS-defining cancers” (that is, Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer) fell in most age groups, from 34,587 cancers during 1991-1995 to 10,325 cancers during 2001-2005. (A diagnosis of any one of these cancers can mark the point at which HIV infection has progressed to AIDS, which is why doctors call them “AIDS-defining.”)

In contrast, the estimated number of other cancers among the study subjects living with HIV nearly tripled, from 3,193 during 1991-1995 to 10,059 during 2001-2005. New cases of anal, liver, and lung cancers and Hodgkin lymphoma accounted for about half of the increase.

The authors proposed that the growing number of non-AIDS-defining cancers will require greater attention to cancer prevention and early detection among HIV-infected people. In addition, they stated, more research is needed to appropriately tailor cancer treatments to people with HIV. “As the HIV-infected population in the United States continues to grow and age, cancer will emerge as an important public health issue,” concluded the paper’s senior author, Dr. Eric A. Engels of DCEG.

GeneticStudy Yields New Clues to Melanoma

In the largest genetic survey of melanoma tumors to date, researchers have sequenced the genes of 14 untreated patients with advanced disease. The results, published online in Nature Genetics on April 15, point to additional genes and pathways not previously associated with melanoma that may play a role in the disease.

Dr. Yardena Samuels of the National Human Genome Research Institute and her colleagues sequenced the protein-coding genes (also called the exome) of tumor cells and of matched normal cells from the same individuals. The tissue samples came from patients subsequently treated by study co-author Dr. Steven Rosenberg, chief of the Surgery Branch in NCI’s Center for Cancer Research.

The sequencing revealed alterations in 16 genes that may contribute to the disease. Among these, only the BRAF gene had been linked to melanoma previously. In an unexpected finding, the researchers discovered the same mutation in a gene called TRRAP in six different individuals with melanoma. TRRAP encodes a protein that helps control cell proliferation. The recurrent nature of the mutation at the same amino acid location suggests that it plays a role in the disease, the researchers noted.

Recurrent mutations were also found in a gene called GRIN2A. (The protein product of GRIN2A is a subunit of a type of glutamate receptor.) In a larger analysis of 135 melanoma tumors, the gene was mutated in 25 percent of the samples, making it one of the most highly mutated genes in melanoma identified so far. An analysis of signaling pathways confirmed that the glutamate pathway may play a role in melanoma, as had been reported previously in Nature Genetics.

“This is the most comprehensive view of the melanoma genetic landscape to date,” said Dr. Samuels, noting that many more genomes need to be sequenced to understand the genetic picture of the disease completely. The work builds on an earlier study by the same group that involved sequencing families of genes. A single whole-genome sequence of a patient with melanoma was first reported last year by researchers at the Wellcome Trust Sanger Institute.

“We can derive genetic data from tumors efficiently, and we can do the analysis,” Dr. Samuels said. “But the main challenge will be to find out which of the mutations are important in the disease and apply the findings to patient care.”

SignalingMolecule Selectively Kills Breast Cancer Cells

Normal breast cells (mammary epithelial cells, or MECs) secrete a signaling molecule that kills breast cancer cells but does not harm healthy cells, researchers have found. The signaling molecule, known as interleukin-25 (IL-25), binds to receptors on the surface of breast cancer cells and triggers cell death. The findings appeared in Science Translational Medicine on April 13.

Dr. Saori Furuta of Lawrence Berkeley National Laboratory (LBNL) and her colleagues used a three-dimensional (3D) cell-culture system to study the growth and development of normal MECs and breast cancer cells. The 3D culture system, which simulates the structure of normal breast tissue, was developed in the laboratory of Dr. Mina Bissell of LBNL. She co-led the study with Dr. Wen-Hwa Lee of the University of California, Irvine.

The researchers identified six molecules produced by normal breast cells grown in 3D culture that either killed breast cancer cells or suppressed their growth. Of those six molecules, IL-25 had the most potent cell-killing (cytotoxic) effects on breast cancer cells grown in the 3D system.

“The cytotoxic activity of IL-25 was restricted to cancer cells that express the receptor IL-25R on the cell surface,” said Dr. Furuta. Additional experiments showed that, when IL-25 binds to its receptor, it sets off a process known as programmed cell death, or apoptosis. The body normally uses this process to eliminate unneeded or abnormal cells.

“IL-25 is naturally produced by healthy breast tissue and thus could be a natural defense mechanism against cancer,” Dr. Furuta noted.

Injecting mice with IL-25 once a day for 1 month dramatically slowed the growth of tumors formed by implanting human breast cancer cells in the mice but did not affect healthy breast tissue or other body tissues that the researchers examined.

The researchers also analyzed 69 human breast cancer biopsy samples and found that 19 percent of those samples were IL-25R-positive. “Importantly, these IL-25R-positive tumors were highly invasive and correlated to poor clinical outcome of patients,” Dr. Furuta said.

“These data suggest strongly that the IL-25/IL-25R signaling pathway may provide novel targets for treating aggressive breast cancers” that express the IL-25 receptor, the study authors conclude.

The researchers have patented their findings and are in the process of transferring the technology to a pharmaceutical company for further development, Dr. Furuta explained.

Also in the News: ASCO Recommends Tumor Testing for Some Lung Cancer Patients

The American Society of Clinical Oncology (ASCO) has issued a Provisional Clinical Opinion (PCO) recommending that patients with advanced non-small cell lung cancer have their tumors tested for mutations in the gene that encodes epidermal growth factor receptor (EGFR) prior to taking drugs that inhibit signaling from EGFR as a first-line therapy. Patients whose tumors test negative for these mutations may benefit more from chemotherapy than from an EGFR inhibitor, such as erlotinib (Tarceva) or gefitinib (Iressa), according to the April 11 PCO.

“For patients who do not have the [EGFR] mutation, giving erlotinib first is not the right thing to do,” co-author Dr. Giuseppe Giaccone, chief of the Medical Oncology Branch at NCI’s Center for Cancer Research, said in a statement. “It does not work as well for those patients, and we may be losing the opportunity to give chemotherapy, which could be more effective.”

The PCO, which is intended to provide direction to doctors, is based on the results of five phase III clinical trials. At ASCO’s request, NCI’s Physician Data Query (PDQ) Adult Treatment Editorial Board provided a written analysis of the results of one of the trials, the IPASS study.

A Conversation With

Inside NCI: A Conversation with Dr. Lauren Wood about Cancer Vaccines and Health Disparities

A senior clinical investigator in NCI’s Vaccine Branch discusses the most recent advances in immune-based therapies and how clinical trials are important to the work she does. She also highlights why Minority Cancer Awareness Week is important and why barriers to clinical trials participation among minority populations still exist.  

You must have flash installed and enabled to view the video.

Video produced and edited by Sarah Curry

Spotlight

Investigating Nature's Mysteries for Drug Development

Artist's rendering of colorful marine invertebrates Organisms—including marine invertebrates—are collected from around the world and sent to NCI where researchers look for compounds that show potential anticancer activity.

Living in the competitive environment of a coral reef, marine invertebrates, such as delicate sea squirts and immobile sponges, must find creative ways to protect themselves. For some organisms, having an arsenal of toxic chemicals is what keeps them alive. Scientists in NCI-Frederick's Natural Products Branch (NPB) are exploring ways to harness these chemicals, and those from other plant, animal, and microbial sources, for drug discovery.

Interest in natural products for drug development has waxed and waned, but there's no denying their importance in oncology, according to NPB Chief Dr. David Newman. Today, over half of the drugs approved to treat cancer come from a natural product or a natural product prototype.

At NCI-Frederick, researchers look for active toxic compounds from natural sources, explained Dr. Newman, then modify those compounds, if necessary, to maintain their potency while simplifying their complex molecular structures. NPB works with other NCI programs, collaborators in academia and the pharmaceutical industry, and governments of countries supplying natural product sources, and may join in the development of products with these collaborators at any stage of development.

Biological Detective Work

NPB, part of NCI's Developmental Therapeutics Program (DTP), has existed for more than 50 years. The collection and compound extraction process was systematized 25 years ago and has essentially stayed the same since. (See the accompanying video.)

Organisms—marine invertebrates, plants, and microorganisms—collected from around the world are sent to NPB, where researchers look for compounds that show potential anticancer activity when screened against the NCI-60 panel of human cancer cell lines. That project, also managed by DTP, uses 60 different human tumor cell lines, representing leukemia, melanoma, and cancers of the lung, colon, brain, ovary, breast, prostate, and kidney to screen both synthetic compounds and natural product samples.

The first step of the extraction process begins with grinding up the organism and sending it to an extraction lab. Solvents are then added and two extracts are produced; one contains compounds that are soluble in water, and the other contains materials that are insoluble in water.  Dr. Newman explained that an extract is like a library; each extract can have anywhere from 50 to more than 100 compounds, like a library with different books.

"We don't know which book refers to which target, or which book tells a story," Dr. Newman said. The extracts are tested against the NCI-60 panel of cells lines in the laboratory, and then the most promising are tested in animal models of a variety of tumor types to look for anticancer properties.

When they find a "hit," the extract is sent to the isolation lab to identify which book, or books, in the library of compounds is responsible for the biological activity of the extract. The researchers separate individual chemical compounds from the extract through a process known as bioactivity-driven chromatography. Once in a pure state, the compounds are studied to define their chemical structures using state-of-the-art instrumentation. These include mass spectrometry for determining the size or molecular weight of a compound, and nuclear magnetic spectroscopy, which reveals how atoms within a molecule are linked together. 

Unraveling the Complexities of Natural Compounds

Compounds from nature are often quite complex structurally. Until the advent of new chromatography-based analytical techniques roughly 10 years ago, it could take anywhere from 6 months to a year to isolate and identify a compound. Natural products research was criticized for that slow pace, Dr. Newman explained. Now researchers can often find an answer in 1 to 2 weeks. And because of these improvements, materials found today can be developed into testable treatments faster.

You must have flash installed and enabled to view the video.
Video produced and edited by Sarah Curry.

Another hurdle is finding enough of the source material to sustain the drug development process. The need to find sustainable sources in nature led researchers to shift their focus from macro-organisms, such as marine invertebrates, to micro-organisms that can be cultured in the lab and induced to make compounds in quantities that will provide a continuous source.

"That helped with the supply issue, but it still didn't address the problem of these compounds being really complex," said Dr. Chris M. Ireland, a long-time researcher in the field and dean of the University of Utah's College of Pharmacy.

Some chemists thought that, when combinatorial chemistry took off in industry in the 1990s, that it could be used to create "libraries" of molecules that would be similar to those obtained from natural products. Combinatorial chemistry enables researchers to create a large number of different but structurally similar compounds. However, it has yet to showcase the structural complexity and diversity that can be found in natural products.  "Where combinatorial chemistry is magnificent, though, is taking an active structure and modifying it," Dr. Newman said.

"That's exactly what Harvard and [the pharmaceutical company] Eisai did with halichondrin B," a natural compound from deep-sea sponges that had shown promising antitumor properties, he continued.

Deep Sea Sponge Inspires Cancer Drug

The cancer drug eribulin mesylate (Halaven) was modeled after halichondrin B. Eribulin interferes with the assembly and disassembly of microtubules, cellular structures that help move chromosomes during cell division. Other cancer drugs, including vinca alkaloids and taxanes, also disrupt microtubules. But eribulin has unique tubulin interactions, and in early animal studies it was found to work better against breast and lung cancer than either its parent natural compound, halichondrin B, or the commonly used drug paclitaxel.

The eribulin story, which spans nearly three decades of research, is based on basic research in synthetic organic chemistry. In 1982, when Japanese researchers initially isolated halichondrin B, the prospect of developing a synthetic version of such a complex compound seemed impossible with the technology available. But in 1987, Dr. Yoshito Kishi, a researcher in the Department of Chemistry and Chemical Biology at Harvard, and his colleagues decided they were up to the challenge.

Dr. Kishi considered the compound a good candidate to showcase the potential of a new carbon–carbon bond-forming reaction he and his team had discovered. Additionally, halichondrin B had demonstrated antitumor activity in mouse models of some human tumors.

By 1992, the Harvard team had completed total synthesis of the complex molecule. "By chance we found the right half of halichondrin B had the [antitumor] properties we were looking for, so I applied for a patent," Dr. Kishi said. 

Dr. Kishi was working with chemists and biologists at Eisai to convert his synthesis into the molecule that would eventually become eribulin. In the process, they made over 200 derivatives. "Because of its unprecedentedly complex structure, there were internal and external concerns for Eisai to develop eribulin further," he explained.

Researchers from NCI-Frederick's NPB, meanwhile, were working independently with very small amounts of material from the sponges that produce halichondrin B to isolate the active compound, and the compound was subsequently approved for initial preclinical evaluation.

Various scientific equipment used in the natural products extraction processAt NCI’s Natural Products Branch, researchers use a intricate extraction process to create a “library” of compounds that show biological activity.

In 1998, NPB and Eisai combined efforts to evaluate Eisai's two best synthetic compounds and the purified natural halichondrin B compound to see which one performed the best in animal models.

"One of Eisai's compounds trumped the others, and so NCI and Eisai came up with a Cooperative Research and Development Agreement, and a phase I trial began in 2001," Dr. Newman recounted. The promising results of the trial led Eisai to begin full-scale clinical development.

Last November, the FDA approved eribulin to treat late-stage metastatic breast cancer in patients who have completed two or more rounds of chemotherapy. (See related Research Highlight.)

A Bright Future for Marine-Sourced Medicines

Dr. Newman and Dr. Ireland agree that, due to halichondrin B's structural complexity, no synthetic chemist would, "in their wildest imagination," ever have dreamed of creating the compound that inspired eribulin, or, for that matter, paclitaxel (which was originally developed from the Pacific Yew tree). Eribulin is now being tested for its potential use in the treatment of other solid tumors, including non-small cell lung cancer, prostate cancer, and bladder cancer.

However, eribulin is only the second cancer drug from a marine source that has been approved. The other is trabectedin (Yondelis), which was approved by the European Union in 2007 to treat soft tissue sarcomas. "The fact that these … drugs have come out within the past few years is huge," Dr. Ireland said. "The future looks good for marine organisms as a source.

"There is the realization that nature provides us with unique chemicals," Dr. Ireland said. "And now the tools are available to take those molecules that nature gives us and optimize those structures to make drugs to treat ailments that have been around for centuries."

Sarah Curry

A Closer Look

Debunking Cancer Myths, One Phone Call at a Time

Reader Suggested

When Melissa Hoard Silver picks up the phone at work, she never knows where the conversation will lead. Her calls come from people seeking information about cancer who dialed 1-800-4-CANCER. Although her primary job is to provide information and support, she also welcomes the opportunity to debunk some myths about the disease.

Rendering of Hercules slaying the mythical creature Hydra Some cancer myths – for example, that cancer is contagious -- continue to persist among the public.

"We give people reliable information about cancer at what is often a difficult time for them," said Silver, who has been with NCI's Cancer Information Service (CIS) for 4 years. "And as we support them, we can also share what the research says about a particular myth or question."

One of the most common myths that Silver encounters is the idea that cancer is contagious. In a recent call, a woman asked whether she could safely share a bathroom with a cousin who was coming to visit. "My cousin has cancer," the woman explained, saying that she did not want to "catch" the disease.

"We reassure people that no one can 'catch' cancer from another person," said Silver. "For people who are wondering if they can still hug their loved ones without getting cancer, this information can really put their minds at ease."

But Silver and the other information specialists with the CIS also tell people what the research shows about cancer and infectious agents, such as viruses. They explain that, although cancer is not contagious, infection with certain strains of the human papillomavirus can increase the risk of developing cervical and some other types of cancer, including some forms of head and neck cancer.

Selected NCI resources used by CIS information specialists

Cancer Causes and Risk Factors
(This includes information on hair dyes and cancer risk; antiperspirants/deodorants and breast cancer; artificial sweeteners and cancer; and psychological stress and cancer.)

What You Need To Know About™ Cancer—Risk Factors

Evaluating Health Information on the Internet

PDQ (Physician Data Query): Prevention Summaries
(Information about the known causes and risks for specific cancer types)

Additional resources

American Cancer Society: Rumors, Myths and Truths

American Society of Clinical Oncology: Cancer Myths

The Johns Hopkins Sidney Kimmel Comprehensive Cancer Center: Cancer Update Email—It's a Hoax!

Food and Drug Administration: Beware of Online Cancer Fraud

Federal Trade Commission: Cure-ious Web Site

Myth Busting with Evidence

At the CIS Contact Center in Seattle, Washington, nearly 70 information specialists handle approximately 100,000 phone calls, e-mails, and live chat sessions annually. To give their clients the most relevant and up-to-date evidence, the staff draws on a variety of resources, including NCI Web sites and publications. (See sidebar.)

The information specialists address some cancer myths directly. For instance, a person may send an e-mail asking NCI to verify a suspicious claim on the Internet. Or a myth may emerge organically during an extended phone conversation.

"Cancer myths may not be the focus of the call, but we work hard to understand what else is going on with a person," said Silver. "The myth may be woven into the conversation, and we can pick up on these clues as we talk."

Just about every common cancer myth in the United States has been discussed by the CIS since the service was established in 1975. "Some of these myths have not changed much over the last few decades," said Randy Jacobs, an oncology nurse educator with the CIS for more than 20 years. "What's changed is the Internet." 

Indeed, some cancer myths could live online forever. Consider an email falsely attributed to Johns Hopkins University that began to circulate in 2004 and made unsubstantiated claims about cancer. (For instance, the e-mail said that cancers feed on certain foods, including sugar.)

The message was a hoax, and Johns Hopkins issued a detailed statement responding to the claims. But 7 years later, people are still asking the CIS if eliminating sugar from the diet of a loved one will cause the person's cancer to go away.

Johns Hopkins noted in its statement that a poor diet and obesity can increase the risk of developing cancer. "However, there is no evidence that certain foods alter the environment of an existing cancer, at the cellular level, and cause it to either die or grow," the statement said. More recently, the CIS has fielded questions about a myth that all cancers are caused by a fungus and that baking soda is the cure.

"People ask what the research shows about a particular topic, but often there is no research related to the question at hand," said Susan Church, who responds to public inquiries at the CIS. "Sometimes, all we can do is explain what we know to date about the biology of cancer."

Blaming Surgery

Another common belief is that having a biopsy or surgery for cancer will cause the disease to spread. According to NCI, this is a very rare occurrence because surgeons are aware of the potential risk and take precautions to prevent cancer cells from spreading during surgery.

Why so many people fear that surgery will spread cancer is not clear. The fears may be related to the fact that surgery can show that a person's cancer was farther along than anyone had realized prior to the surgery. But, although the most likely explanation for this is the limitations of clinical exams and detection tools, some people mistakenly blame the surgery itself.

"This has been a consistent belief over the past 20 years," said Laura Rankin, a resource specialist with the CIS. "Many people will tell us that my mother had surgery, and the cancer was everywhere. They blame surgery."

For some people, added Deborah Pearson, an NCI public health advisor, "it can be difficult to grasp the idea that a person was living with an advanced cancer for a long period of time without it causing problems sooner."

Scientific evidence is perhaps the best tool for combating myths. A decade ago, the CIS responded to many questions about shark cartilage as a cancer cure. In the years since, different extracts of shark cartilage were developed as drugs and tested in clinical trials. Unfortunately, these extracts did not help patients with breast, colon, or lung cancer.

"Having the information from the clinical trials—the evidence—does seem to make a difference," said Pearson. "The results have been out there, and people just know that shark cartilage is not an effective treatment for cancer." (Information about cartilage and cancer is available, for example, in NCI's comprehensive cancer database, known as PDQ.)

Debunking Cancer Myths Online

Melissa Hoard Silver Melissa Hoard Silver answers callers at NCI's Contact Center located at the Fred Hutchinson Cancer Research Center in Seattle, Washington

Although the Internet has created new ways to spread myths about cancer, it also has credible information debunking these myths. NCI has published fact sheets about cancer myths and how to evaluate information on the Internet, for instance.

In addition, the American Cancer Society, the American Society of Clinical Oncology, and Johns Hopkins, among others, have Web sites about cancer myths. (See sidebar.)

"Many of the myths may speak to people's lack of knowledge about health in general and fears about cancer in particular," said Judy Petersen, an oncology nurse educator with the CIS. "We realize there are many unknowns about the disease, and people may be inclined to believe things that are not true."

In her phone conversations, Silver tries to "meet people where they are." If someone raises a question about a myth, she'll often say, "That's a great question—it's a common question," and then direct the person to helpful information.

"We're just happy to help our callers in any way that we can," she added.

Edward R. Winstead

Further reading:

NCI's Cancer Information Service: Providing Information and Assistance Nationwide

Featured Clinical Trial

Cediranib to Treat Alveolar Soft Part Sarcoma

Dr. Shivaani Kummar Dr. Shivaani Kummar

Name of the Trial
Phase II Study of Cediranib (AZD2171) in Patients with Alveolar Soft Part Sarcoma (NCI-09-C-0192). See the protocol summary.

Principal Investigator 
Dr. Shivaani Kummar, NCI Center for Cancer Research

Why This Trial Is Important  
Alveolar soft part sarcoma (ASPS) is an extremely rare type of soft-tissue sarcoma that typically affects teenagers and young adults. It usually develops in the muscles or deep soft tissue of the legs, but it can also arise in the trunk of the body, the head and neck region, and the arms. ASPS is a slow-growing cancer, and it often does not produce symptoms until it has reached an advanced stage. Consequently, the long-term outlook for patients with this type of cancer is poor.

Surgery is the most effective treatment for ASPS, but many patients have widespread metastatic disease by the time they are diagnosed and are not candidates for surgical treatment. In addition, chemotherapy regimens that have been used to treat other types of soft tissue sarcoma are not effective in patients with ASPS. There is currently no accepted standard of care for advanced ASPS.

Cediranib is an experimental drug that blocks the activity of a number of proteins important to the growth of new blood vessels to tumors, a process known as tumor angiogenesis. Because ASPS tumors are highly angiogenic, doctors want to know if cediranib will be effective in slowing or stopping their growth. In early trials of the drug, patients with ASPS showed some partial responses or disease stabilization. Based on these findings, researchers at NCI are conducting a phase II clinical trial of cediranib in ASPS patients.

In this trial, patients with metastatic ASPS will be treated with cediranib by mouth once a day in 28-day cycles until disease progression or unacceptable toxicity. Doctors will monitor patients for signs of tumor shrinkage and possible side effects of treatment.

“Cediranib is showing preliminary activity in this disease, and, given that no other systemic treatment is effective, I think cediranib presents an option for these patients,” said Dr. Kummar. “In order to evaluate the drug further in this disease, we’ve expanded the trial to enroll more patients.”

Once accepted into the study, patients will visit the NIH Clinical Center every 2 to 4 weeks for examination and to receive the study medication. Travel assistance may be available.

For More Information
See the lists of eligibility criteria and trial contact information or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.

An archive of "Featured Clinical Trial" columns is available at http://www.cancer.gov/clinicaltrials/featured.

FDA Update

FDA Approves New Treatment for Medullary Thyroid Cancer

On April 6, the Food and Drug Administration (FDA) approved vandetanib (Zactima) to treat adult patients with unresectable or metastatic medullary thyroid cancer (MTC). This is the first approved drug treatment for MTC.

The efficacy of vandetanib was demonstrated in an ongoing, randomized, international study of 331 patients with late-stage MTC who were treated with vandetanib or placebo. Patients taking vandetanib had a longer period of time without disease progression compared to those receiving the placebo.

Because serious side effects were associated with vandetanib use including, in some cases, an irregular heart rhythm that could lead to death, the drug is being approved with a Risk Evaluation and Mitigation Strategy (REMS). Only physicians and pharmacies certified through the vandetanib REMS program will be able to prescribe or dispense the drug.

Vandetanib is a small molecule inhibitor of several cell-surface receptors such as RET, which is mutated in hereditary forms of MTC. Blocking these receptors inhibits cancer cell proliferation and migration.

“Vandetanib’s approval underscores FDA’s commitment to approving treatments for patients with rare and difficult to treat diseases,” said Dr. Richard Pazdur, director of the FDA’s Office of Oncology Drug Products.

Advisory Panel Recommends Targeted Therapies for Treating Rare Pancreatic Tumors

At its April 12 meeting, the FDA’s Oncologic Drugs Advisory Committee voted to recommend approval for everolimus (Afinitor) and sunitinib (Sutent) to treat advanced pancreatic neuroendocrine tumors (PNET). Although the FDA is not required to follow the suggestions of its advisory committees, it typically does.

PNET are a relatively uncommon tumor type, with fewer than 1,000 patients diagnosed yearly in the United States. These tumors tend to have a better prognosis than other pancreatic tumors, but few treatments are available if they recur.

Both everolimus and sunitinib are currently approved as treatments for advanced renal cell carcinoma. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway, causes immune suppression and reduces cell proliferation and tumor blood vessel growth. Results from a randomized clinical trial showed that the time to disease progression for patients taking everolimus was more than double that of patients taking a placebo (11 months versus 4.6 months).

The data supporting sunitinib, a small molecule receptor tyrosine kinase inhibitor that blocks cell proliferation and tumor blood vessel formation, were less clear. The randomized clinical trial testing sunitinib against a placebo in patients with advanced PNET was stopped prematurely and showed a smaller benefit than that detected with everolimus.

Both drugs are known to have serious side effects, including kidney failure. Sunitinib has also been linked to heart failure.

FDA Initiates Safety Review of Myeloma Drug for Possible Cancer Risk

The FDA announced on April 8 that it is reviewing results from several clinical trials to investigate a potential association between lenalidomide (Revlimid) use by patients with multiple myeloma and an increased risk of developing new cancers.

Lenalidomide, an analog of thalidomide, is thought to promote cancer cell death, stimulate immune cell activity, and prevent the development of tumor-associated blood vessels. The drug is approved to treat myelodysplastic syndromes and can be used in combination with dexamethasone to treat multiple myeloma.

Currently, the FDA does not recommend delaying, modifying, or restricting the use of lenalidomide for patients being treated according to FDA-approved indications. However, health care professionals and patients are encouraged to report adverse events or side effects related to treatment with lenalidomide to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

The FDA will communicate any new recommendations once the safety review is completed.

Cancer.gov Update

NCI Recovery Act Web Site Highlights Small Businesses Driving Innovation in Cancer Care

Two researchers working at a computerWith the help of ARRA funds, BioFortis upgraded its technology platform (Labmatrix), which helps researchers evaluate large amounts of data more efficiently

The NCI Recovery Act Web site features a new article about two small businesses that have been able to advance new technologies to improve cancer care with the support of funding made available by the American Recovery and Reinvestment Act (ARRA), also known as the Recovery Act. 

The two companies, Columbus Nanoworks and BioFortis, have also received funding from NCI’s Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs, which fund small businesses to stimulate technological innovation and collaboration.

The combined assistance is allowing the small businesses to advance potentially life-saving technologies and products. Columbus Nanoworks is developing magnetic nanoparticle reagents for the detection of cancer cells, and BioFortis upgraded its technology platform (Labmatrix), which helps researchers evaluate large amounts of data more efficiently.

Notes

NCI Cancer Classroom Webinar Series Kicks Off April 26

NCI’s Office of Communications and Education will present a free, four-part webinar series, Cancer Classroom, for early career public health professionals or those new to the field of oncology. This series provides the educational guidance, tools, and resources necessary for professionals to address cancer as a public health issue. Topics include understanding cancer and the clinical trials process.

Upon completion of the series, participants will be able to demonstrate a basic understanding of cancer etiology, screening, diagnosis, and treatment; learn the risks and benefits of trial participation; understand trial participant protections; and identify barriers to enrollment and unique recruitment challenges and learn strategies to overcome them.

The workshops are free, but pre-registration is required. To register or learn more, visit the NCI Cancer Classroom Series Web site. All workshops will take place on Tuesdays from 2:00 p.m. to 3:30 p.m. EDT on the following dates:

  • April 26–Understanding Cancer: Cancer Prevention and Screening
    Featured speaker: Linda Parreco, public health advisor, NCI
  • May 17–Cancer Diagnosis, Treatment and Supportive Care
    Featured speaker: Annette Galassi, public health advisor, NCI
  • June 28–Clinical Trials 101
  • July 26–Clinical Trials 102

Breast Cancer Guidelines Proposed for Low- and Middle-Income Countries  

Cover of the April 1 issue of the medical journal The BreastThe April 1 issue of The Breast

The Breast Health Global Initiative (BHGI), a global network of organizations dedicated to improving breast health in medically underserved women, published a supplement on challenges to breast cancer screening and treatment in low- and middle-income countries in the April 1 issue of The Breast. The supplement, “Global Breast Health Care: Optimizing Delivery in Low and Middle Resource Countries,” includes three consensus statements and 11 research papers based on projects and proposals presented last June at the BHGI Global Summit on International Breast Health in Chicago. The summit brought together experts from 43 countries.

Dr. Joe Harford and Isabel Otero of NCI’s Office of International Affairs co-authored one of the report’s consensus statements, entitled “Problem solving for breast health care delivery in low- and middle-resource countries (LMCs): consensus statement from the Breast Health Global Initiative.” The statement discusses the strengths and weaknesses of health care systems in those countries in relation to the cancer burden. The authors recommended an evidence-based approach to creating cost-effective cancer control initiatives in poorly studied populations.

The supplement illustrates a growing recognition of noncommunicable diseases, such as breast cancer, as substantial contributors to the disease burden in low- and middle-income countries, which are often not fully prepared to deal with growing incidence rates.

An executive summary of the consensus statements was published simultaneously in the April 1 issue of The Lancet Oncology.

“It is the hope of the authors that this consensus analysis will help scientists, policy-makers, and health care administrators optimize breast health care management in populations with limited resources,” said Ms. Otero. “The guidelines encourage the use of implementation science, qualitative and quantitative research, and cost-benefit analyses to guide the establishment or improvement of breast cancer control programs for the millions of underserved women around the world.”

Two-Year Project Launched to Standardize Cytogenetic Testing in Mexico  

On April 8, NCI’s Office of Latin American Cancer Program Development (OLACPD), in partnership with the American Society of Hematology (ASH) and the Agrupación Mexicana para el Estudio de la Hematología (AMEH), held a workshop in Mexico City to discuss the standardization of cytogenetics laboratory protocols. The workshop served as the official launch of a 2-year initiative designed to improve cytogenetic analysis, which plays a central role in treating patients with acute myeloid leukemia (AML).

AML is the most common form of leukemia in adults and one of the most common forms in children. Cytogenetics identifies abnormal genetic structures in leukemia cells, and a patient’s cytogenetic profile is the most important prognostic factor in AML. High-quality, consistent testing practices increase the likelihood that patients with AML will receive appropriate care.

Four laboratories in Mexico were selected to participate in the 2-year program, which is sponsored and overseen by a team of U.S. and Mexican scientists. A steering committee composed of experts from NCI, ASH, and AMEH will periodically review the laboratories’ data and provide each laboratory with a quarterly summary of its performance, including feedback on operations.

The ultimate goal of this pilot project is that the standardization of cytogenetics testing will improve the quality of the work and allow the laboratories to serve as models for other facilities throughout Mexico.

“Stupid Cancer Show” to Host Program on Clinical Trials Myths

NCI’s Dr. Nita Seibel and Steven Friedman will be among the guests discussing myths about clinical trials on an upcoming episode of the Stupid Cancer Show, a radio webcast program produced by I’m Too Young For This Cancer Foundation. The episode will air on April 25th at 8 p.m. ET. To speak with the host, call (347) 215-6845. You can also listen to archived programs.

The Stupid Cancer Show is an award-winning international talk radio webcast that gives voice to more than 70,000 young adults (aged 15 to 39 years old) who are diagnosed with cancer each year. To learn more about organizations that support young people with cancer, visit NCI’s portal for Adolescents and Young Adults with Cancer.