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June 26, 2012 • Volume 9 / Number 13

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Many Survivors of Adolescent and Young Adult Cancers Have Chronic Health Problems, Unhealthy Behaviors

A teenage girl looking out a windowSurvivors of adolescent and young adult (AYA) cancers have worse health and unhealthier behaviors than people without a history of cancer, a new analysis shows. These survivors smoke more and exercise less, and they have a higher prevalence of chronic medical conditions and obesity, poorer mental and physical health, and more financial barriers to medical care access.

Results of the study, which used data from the Centers for Disease Control and Prevention's (CDC) 2009 Behavioral Risk Factor Surveillance System, were published June 11 in Cancer. Read more > >


Communications SeriesOncology Nursing Series
Survivorship Series Technology Series

Series Archives Now Available

This issue features several stories related to cancer survivorship. For more stories from the NCI Cancer Bulletin on this topic, click on the survivorship icon. 

The Bulletin publishes six other series—technology, communications, oncology nursing, advocacy, global health, and cancer centers—each with its own icon. Click on the icons to access all of the articles in each series. Look for additional articles on these and other topics in the future.



  • Legislative Update

    • Congress Passes FDA User-Fee Legislation to Address Drug Shortages
  • Update

    • Blog Aims to Stimulate Fresh Thinking on Cancer Epidemiology
  • Notes

    • NCI Advisory Boards Hold Joint Meeting This Week
    • William Dahut Named Deputy Director of NCI's Center for Cancer Research
    • Research to Reality Cyber-Seminar: How to Measure Health Disparities
    • NCI Community Health Expo Will Feature Genomics, Biospecimens Research

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

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Featured Article

Many Survivors of Adolescent and Young Adult Cancers Have Chronic Health Problems, Unhealthy Behaviors

Survivorship icon

Survivors of adolescent and young adult (AYA) cancers have worse health and unhealthier behaviors than people without a history of cancer, a new analysis shows. These survivors smoke more and exercise less, and they have a higher prevalence of chronic medical conditions and obesity, poorer mental and physical health, and more financial barriers to medical care access.

Results of the study, which used data from the Centers for Disease Control and Prevention’s (CDC) 2009 Behavioral Risk Factor Surveillance System, were published June 11 in Cancer.

“There has been an increasing amount of literature showing that AYA cancer patients have experienced fewer improvements in survival compared with younger children and older adults, so we decided to take a closer look at that population,” explained lead author Dr. Eric Tai, a medical officer in the CDC Division of Cancer Prevention and Control.

To learn more about the health status of survivors of AYA cancers, Dr. Tai and his colleagues analyzed survey responses from 4,054 people who had first been diagnosed with cancer between the ages of 15­ and 29 and more than 345,000 people without a history of cancer.

Self-Reported Risk Behaviors, Chronic Conditions, and Health StatusSelf-Reported Risk Behaviors, Chronic Conditions, and Health Status (Source: Behavioral Risk Factor Surveillance System, 2009)Source: Behavioral Risk Factor Surveillance System, 2009

Compared with people who had no history of cancer, the researchers found that those who’d had cancer as AYAs were more likely to be current smokers, be obese, have various chronic conditions, be disabled, and have poor mental and physical health. Survivors of an AYA cancer were also more likely than those with no cancer history to be unemployed or unable to work and to report not seeking medical care due to concerns about cost.

“I think these findings are a reminder of how vulnerable this population is,” commented Dr. Ashley Wilder Smith, a behavioral scientist in the Outcomes Research Branch of NCI’s Division of Cancer Control and Population Sciences. “There are a lot of psychosocial, educational, employment, and behavioral issues that we really need to be attending to for this group of cancer survivors.”

For example, the CDC researchers believe that interventions to prevent AYA cancer survivors from starting to smoke and to help them quit should be a priority. “This is especially true for adolescents,” they noted, “because their intention to smoke is closely correlated to future smoking.”

A teenage girl looking out a windowA new analysis shows there is a need for better follow-up care for survivors of adolescent and young adult cancers.

The study authors also noted the low rate of proper follow-up care for this population: “Most AYA cancer survivors are not followed in cancer survivorship programs and often are cared for by primary care physicians who may be unaware of the risks associated with AYA cancer and therapy,” they wrote.

One way that health providers can improve the health of AYA cancer survivors is by developing individualized survivorship care plans, as recommended by the Institute of Medicine in a 2005 report, Dr. Tai said. (See the related story in this issue.) “Health care providers really need to utilize established follow-up guidelines for pediatric and AYA patients. Those guidelines can equip providers with information on late effects, risk factors, screening and treatment, and counseling and other interventions that target unhealthy behaviors.”

The medical oncology community should do more to educate primary care providers on the follow-up care these patients need, added Dr. Smith. AYA survivors “are living a long time with a history of chronic disease,” she said. “Plus, there are so many transitions going on in their lives in terms of education, employment, frequent relocations, as well as relationship and family-related issues.” These factors “all tend to interact, making a bit of a perfect storm” that hampers AYA survivors obtaining recommended follow-up care for themselves, she explained. 

Matthew Zachary, an AYA cancer survivor and founder of the advocacy group Stupid Cancer, said he wasn’t surprised by the long-term challenges and risks faced by this survivor population. “A lot of this has long been obvious to those of us who live in the bubble. But it’s really good that more of these studies are coming out now because it gives credence to what we already knew to be true,” he said. “It helps us make the case to the public” about the importance of addressing the special needs and concerns of the AYA cancer population.

See the special issue of the NCI Cancer Bulletin on adolescents and young adults

Specialized AYA programs in cancer treatment centers may be another part of the solution, Dr. Smith believes. Even if a cancer center primarily serves pediatric or adult patients, the facility should have a program “or at least a liaison staff member who is really focused on the needs and issues of the AYA population,” she suggested.

Such programs are being established at some NCI-designated comprehensive cancer centers. But most young adults are treated in community settings, which means that NCI centers and other large academic-based institutions with AYA programs and expertise need to reach out to the community and make their services available to more young adult cancer patients, she commented.

The CDC study “is a key paper because it really highlights the fact that not only do we need to focus on better follow-up care for AYA survivors, but we also need to look at this population more holistically,” said Dr. Smith.

—Bill Robinson

Further reading: “A Conversation with The Who's Roger Daltrey about Teen Cancer Centers

Cancer Research Highlights

Breast Cancers Can Change Biologically as They Progress and Relapse

In many women with recurrent breast cancer, the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status of their tumors changes between treatment for the primary tumor and relapse, a large retrospective study has found. The findings, published June 18 in the Journal of Clinical Oncology, support previous studies that have also detected changes in these biomarkers during cancer progression.

These three biomarkers help doctors choose the best treatments for individual women. Therefore, tumors that recur in the breast or appear elsewhere in the body should be biopsied “as a routine procedure” because the results may influence treatment decisions, recommended the authors led by Dr. Linda Lindström of Cancer Center Karolinska in Sweden.

Dr. Lindström and her colleagues used information from pathology reports for 1,010 women treated at three hospitals in Stockholm, all of whom had biopsies taken from their primary and recurrent breast tumors. All three hospitals had stringent quality-control methods for verifying the accuracy of all three biomarkers.

Primary and recurrent tumors from 459 women were tested for ER expression. In almost 33 percent of those women, the ER status of the tumor changed (ER expression started or stopped) between treatment and relapse. More than 40 percent of the 430 women whose tumors were tested for PR expression had a change in PR status between treatment and relapse. And almost 15 percent of the 104 women whose primary and recurrent tumors were tested for HER2 expression had a change in HER2 status between treatment and relapse.

In women whose cancers relapsed multiple times, similar proportions of changes to biomarkers were observed.

Prior treatment appeared to influence some biomarker changes. For example, women previously treated with hormone therapy were more likely than women who did not receive hormone therapy to have changes in tumor ER expression. The authors also found that women with ER-positive primary tumors that lost ER expression at relapse had a higher risk of death than women with stable tumor ER expression.

Treatment for metastatic breast cancer is often based on primary tumor characteristics. For some patients, biopsy results will show that the tumor has changed. Therefore, “verifications will be important and may change management options,” concluded the authors.

World Health Organization Classifies Diesel Exhaust a Human Carcinogen

On June 12, the International Agency for Research on Cancer (IARC), part of the World Health Organization, classified diesel engine exhaust as carcinogenic to humans (a group 1 carcinogen). The decision was based on an IARC working group’s opinion that the body of evidence supports an association between diesel exhaust exposure and an increased risk of lung cancer. The working group also found a positive association—though with limited evidence—between diesel exhaust exposure and bladder cancer.

IARC published a summary of the working group’s evaluation in Lancet Oncology on June 18.

In 1988, IARC classified diesel exhaust as probably carcinogenic to humans (a group 2A carcinogen), and in 1998 an agency advisory group recommended a priority review of the association. The revised classification is based on results from several large human studies, including the recently published Diesel Exhaust in Miners Study (DEMS), led by NCI and the National Institute for Occupational Safety and Health.

“We are pleased that data from our study played an important role in the re-evaluation by providing some of the strongest evidence of an association between diesel exhaust and lung cancer risk,” said Dr. Debra Silverman, chief of the Occupational and Environmental Epidemiology Branch in NCI’s Division of Cancer Epidemiology and Genetics and a lead investigator on the DEMS study.

“There was a tremendous amount of scientific evidence…around the potential harmful effects of diesel exhaust: dozens of epidemiological studies, dozens if not hundreds of laboratory studies in laboratory animals, and then literally thousands of molecular biology and other types of studies looking at fundamental cellular processes and how they’re affected” by diesel exhaust or its constituents, said Dr. Christopher Portier, chair of the IARC working group, at a press conference.

“Our role has been to summarize the scientific evidence and to put that into the public domain” but not to address permissible levels of exposure or other regulatory issues, explained IARC Director Dr. Christopher Wild. “Having provided that evidence base, it’s really then up to national and international regulatory authorities to weigh that [in] the balance with other factors,” he added.

These issues may be particularly important in the developing world, where older, more polluting diesel technology is still widely used and where emissions regulations are lacking, he concluded.

Pre-Existing Mutations May Explain Development of Resistance to Targeted Cancer Drugs

Most patients with advanced colorectal cancer treated with the drug panitumumab (Vectibix) develop resistance to the treatment, and a new study suggests why. Even before patients begin the treatment, a small percentage of their tumor cells may harbor genetic mutations that make the tumors resistant to the drug, researchers reported in Nature on June 13.

Colorectal tumors without KRAS gene mutations usually develop resistance to panitumumab within several months. To study why, Dr. Luis Diaz of the Sidney Kimmel Comprehensive Cancer Center and his colleagues analyzed blood samples from 28 patients for common mutations in the KRAS gene that confer resistance to the drug. The blood samples were collected before treatment and at 4-week intervals during treatment.

Four of the 28 patients were known to harbor KRAS mutations in their tumors, and the researchers detected mutant forms of the KRAS gene in blood samples from 3 of these patients before they began treatment. No KRAS mutations were detected in blood samples obtained before treatment from the 24 patients whose tumor tissue was believed to contain nonmutated KRAS.

An analysis of blood samples taken during treatment indicated that 9 of those 24 patients developed KRAS mutations over the course of treatment. The timing of the appearance of the KRAS mutations was consistent with the time it typically takes for panitumumab resistance to emerge, 5 or 6 months.

The researchers used these findings to develop a mathematical model of tumor evolution in patients who initially responded to panitumumab. The model indicated that tumors probably contained cells with KRAS mutations before the patients started panitumumab treatment. Once treatment started, the number of resistant cells increased. The authors suggest that “resistance is therefore a fait accompli.”

The fact that a substantial proportion of patients in the study developed mutations in a single gene suggests that only a limited number of mutations and genes may confer resistance, the researchers noted. This finding is encouraging because it may be possible to avoid resistance by treating patients with drugs that target at least two pathways, they concluded.

Testing Combination Therapy Could Reveal Clues to Biology of Pancreatic Cancer

A small number of patients with advanced pancreatic cancer have responded to an experimental treatment regimen in which a targeted drug is given alone and then in combination with chemotherapy. Although they are preliminary, the results suggest that some patients with this deadly disease may benefit from the regimen, researchers reported at the Pancreatic Cancer: Progress and Challenges meeting, held June 18–21 in Lake Tahoe, NV.

The 18 trial participants initially received vismodegib (Erivedge) alone for several weeks and then vismodegib plus gemcitabine. After 3 months, half of the patients showed no disease progression or had a partial response. Vismodegib, a pill that is approved for some patients with skin cancer, inhibits the Hedgehog signaling pathway, a growth-promoting pathway that is inactive in most adult tissues but switched on in some pancreatic cancer cells.

The activated Hedgehog pathway may also help prevent chemotherapy drugs from reaching pancreatic tumors by contributing to the development of dense stromal cells around tumors, explained lead investigator Dr. Edward Kim of the University of Michigan Comprehensive Cancer Center at a press briefing. Vismodegib, he suggested, has the potential to alter these cells in a way that makes chemotherapy more effective.

But Dr. Kim noted that even if the combination therapy benefits the patient for a time, cancer stem cells within pancreatic tumors may lead to resistance. These cells are thought to have the ability to self-renew. Previous studies have indicated that the Hedgehog pathway may be more active in pancreatic cancer stem cells than in other pancreatic tumor cells.

A goal of the current trial is to learn whether targeting the Hedgehog pathway in pancreatic cancer stem cells might benefit patients. A comparison of biopsies taken before and after starting vismodegib could show the effects of the drug on the Hedgehog pathway and reveal which patients are most likely to benefit from the regimen.

A trial of another Hedgehog inhibitor in pancreatic cancer was recently stopped after negative results. So it will be important to learn more about this pathway and its role in pancreatic cancer, noted Dr. Daniel Von Hoff of the Translational Genomics Research Institute, who moderated the press briefing.


So Others May Benefit: Young Cancer Patients and Survivors Take Part in Oncofertility Research

Survivorship icon

Young cancer patients are often left partially or completely infertile by the treatments that save their lives. The relatively new field of oncofertility—a discipline that studies ways to assess and offset infertility caused by cancer and its treatment—has emerged to try to help these young men and women.

But to investigate possible solutions, researchers must find patients willing to take part in clinical trials, a difficult task with this age group. To that end, researchers are learning how to better connect with and enroll young patients in studies to improve the ability of future cancer survivors to have children.

Jackie Blachman-ForshayJackie Blachman-Forshay, a thyroid cancer survivor, participates in the Fertility Information Research Study.

Fertility preservation is of special concern for adolescent and young adult (AYA) cancer patients, a group that historically has been underrepresented in clinical research studies. According to Dr. Leonard Sender, editor-in-chief of the Journal of Adolescent and Young Adult Oncology, researchers affiliated with the NIH-funded Oncofertility Consortium (OC) have taken innovative approaches to reach out to adolescent cancer patients and their parents, as well as to young adult patients.

One example is OC’s Fertility Information Research Study (FIRST), an observational registry for young female cancer survivors. “We’re doing FIRST because we don’t have a lot of good information on reproductive outcomes in AYA survivors, and female survivors in particular,” said principal investigator Dr. H. Irene Su, assistant professor of reproductive medicine at the University of California, San Diego.

Dr. Su recalled the initial difficulties that she and her colleagues faced in recruiting for the study. “It’s hard to find AYA patients. We encountered all the issues and barriers other investigators have with reaching these patients,” including physicians’ failure to talk about fertility issues with patients and the high mobility of this group of patients.

Reaching Out through Social Media…

The breakthrough came when Dr. Su and her colleagues capitalized on relationships that OC Director Dr. Teresa Woodruff and her staff at Northwestern University have with several AYA patient advocacy groups, such as Stupid Cancer and Imerman Angels.

“After the initial posting about FIRST on Stupid Cancer’s Facebook page in late 2011, we got 15 calls,” Dr. Su said. After a few months and repeated postings by those organizations, FIRST now has almost 200 participants. “We believe that two-thirds of those came through some sort of social networking site for AYAs,” she said.

When Jackie Blachman-Forshay was diagnosed with thyroid cancer at age 20, she was not told how her treatment might affect her fertility. She later heard about FIRST on Twitter and enrolled in the study. “Once you’re involved in the young adult cancer community, everyone is really well connected,” she noted. “One person posts or tweets something, and pretty quickly everyone knows about it.”

It's difficult to recruit these patients because you're catching them at a very delicate point.

—Kristin Smith, patient navigator

Blachman-Forshay, who is studying for a career in epidemiology research, said she is participating in FIRST because she hopes data about her fertility will be used to create recommendations for clinical practice or to inform doctors how to provide more and better information to AYA cancer patients about fertility preservation.

…and More Traditional Networks

OC researchers have also leveraged the influence of national clinical networks to advance fertility research projects. They created the National Physicians Cooperative (NPC), a network of about 60 fertility clinics across the country, to provide access to human ovarian tissue and a collaborative forum for the exchange of ideas, clinical research methods, and technologies. The network hopes to drive breakthroughs in basic reproductive physiology that will be translated directly to clinical medicine.

In the past year, the creation of the NPC has begun to pay off. Investigators have seen an uptick in enrollment for a study of ovarian tissue cryopreservation, particularly by young women and girls who are unable or unwilling to undergo the standard process of stimulating and harvesting mature eggs for freezing, which can take 2 to 5 weeks to complete before cancer treatment can begin.

The study was launched about 5 years ago in conjunction with the formation of the NPC, according to Dr. Kate Timmerman, OC program director. With a funding grant, the NPC infrastructure is now well established and gaining momentum. As a result, in just the last 12 months, the investigators have nearly doubled the amount of ovarian tissue in their collection and enrolled nearly 50 patients, for a total of 120 patients, she added.

Making Participation Easier

Dr. Woodruff, professor of obstetrics and gynecology at the Northwestern University Feinberg School of Medicine, also credited patient navigators’ knowledge about fertility preservation with helping newly diagnosed young cancer patients, who are often overwhelmed and anxious, to learn about the potential impact of their treatments and the options available, including clinical research studies.

See the special issue of the NCI Cancer Bulletin on adolescents and young adults

Kristin Smith, a fertility patient navigator at Northwestern, said, “It’s difficult to recruit these patients because you’re catching them at a very delicate point. For young adults to be coming into the cancer center, that by itself is scary. Then I start talking to them about, ‘Oh, and by the way, your fertility could be destroyed from all this.’ It’s just way too much for a lot of patients to think about participating in a research study at that time.”

Smith finds ways to make research studies “a little more accessible” to rattled patients by combining participation with other scheduled visits. For example, cancer patients can complete a survey for a study on the impact of stress levels on in vitro fertilization (IVF) outcomes during their mandatory visit with Northwestern’s reproductive endocrinologist, she said.

Dr. Clarisa Gracia, associate professor of obstetrics and gynecology at the Hospital of the University of Pennsylvania, uses a similar “piggyback” approach in recruiting for OC’s ovarian tissue cryopreservation study. “Typically, what works best is adding a study procedure to a needed procedure that’s already scheduled,” she noted.

For example, cancer patients typically get central lines inserted to administer fluids and drugs, and for blood tests. “They’re [already] in the operating room, and that can really make ovarian tissue extraction much more palatable to patients and reduce the risks,” Dr. Gracia said.

Jonny Imerman, founder of Imerman Angels, said he and many other AYA survivors are drawn to give back to the cancer community in appreciation for those who participated in past research studies. He noted that the standard treatments used successfully against his testicular cancer in 2001 were developed decades before. “Someone was on that clinical trial for my treatment protocol, and [their participation] saved my life because the treatment worked,” he said. 

As more young patients and survivors enroll in these fertility studies, researchers hope that their efforts will one day mean that more survivors can look forward to starting a family of their own.

—Bill Robinson

Further reading: “Preserving Fertility While Battling Cancer

A Closer Look

A Tough Transition: Cancer Survivorship Plans Slow to Take Hold

Survivorship icon

Nearly 6 years after undergoing a lumpectomy and radiation treatment for a small tumor in her breast, 49-year-old Kris Batley recently took her last tamoxifen pill.

With the treatment for her breast cancer now complete, Batley is beginning the transition to a new stage of cancer survivorship. Physicians other than her oncologist will now be expected to manage her long-term care, including prescribing follow-up cancer screenings and monitoring her for late effects of treatment.

But is she ready for that transition?

"When I think about it logically, do I really need to see my oncologist 10 to 15 years after I've completed treatment? Probably not," she said. "But I'm only 6 years out, and I feel like, 'I had cancer. I'm a cancer survivor. I need to talk with somebody who knows about cancer.'"

Physician speaking with a patientThe Institute of Medicine recommends that all cancer patients completing treatment receive a survivorship care plan. But many survivors do not receive a plan or are given one that doesn't include critical elements.

Batley's trepidation is just one of a multitude of challenges that many cancer survivors face. These common issues were the impetus for the Institute of Medicine's (IOM) influential 2005 report, From Cancer Patient to Cancer Survivor: Lost in Transition.

The report's central recommendation—made all the more important by the recent estimate that the number of U.S. cancer survivors will increase from the current 13.7 million to nearly 18 million by 2022—was that all patients completing treatment should receive a survivorship care plan (SCP), a blueprint to help survivors navigate the ebbs and flows of post-treatment life. (See the sidebar.)

It's too soon after the report's release to determine whether the use of SCPs improves care, several survivorship researchers agreed. The studies performed to date paint a mixed picture of the progress in refining SCPs so far.

If one thing is clear, noted Dr. Carly Parry of NCI's Office of Cancer Survivorship, it's that there is still a lot to learn about SCPs. "If survivorship care plans are going to become the standard of care," she said, "it's really important that we carefully evaluate their efficacy and viability in the real world."

Growing Pains

The progress in refining and implementing SCPs can be measured several ways.

From the survivor's perspective, "We feel good about what we're hearing, although much of it is anecdotal," said Ellen Stovall of the National Coalition on Cancer Survivorship (NCCS) and a member of the IOM committee that wrote the 2005 report. Survivors appreciate the plans, Stovall continued. "[A plan] helps them know what's coming next, providing some predictability and order to their follow-up care."

But according to two recent studies, one that included only NCI-designated cancer centers and another that included centers that are members of the LIVESTRONG Foundation's Survivorship Centers of Excellence program, many survivors do not receive the plans. And when they do receive them, the plans often fail to include all of the IOM-recommended elements.

The IOM: Essential Components of Survivorship Care

  • Prevention of recurrent and new cancers, and of other late effects
  • Surveillance for cancer spread, recurrence, or second cancers
  • Assessment of medical and psychosocial late effects
  • Intervention for consequences of cancer and its treatment
  • Coordination between specialists and primary care providers to ensure that all of the survivor's health needs are met

Elements to Include in a Survivorship Care Plan

  • Cancer type, treatments received, and their potential consequences
  • Specific information about the timing and content of recommended follow-up
  • Recommendations regarding preventive practices and how to maintain health and well-being
  • Information on legal protections regarding employment and access to health insurance
  • The availability of psychosocial services in the community

The time required to compile the plans—particularly by an oncology workforce that is already stretched thin—is a significant barrier to their broader use, stressed Dr. Carrie Stricker, of the University of Pennsylvania Abramson Cancer Center, who led the study of the LIVESTRONG centers. "Also, we haven't come to a consensus on what the critical elements of [SCPs] should be."

At Wayne HealthCare in Greenville, OH, Dr. Daniel McKellar, a surgeon who directs the hospital's cancer program, and two other staff members are responsible for developing the care plans. They use the SCP template developed by Journey Forward, a public/private collaboration.

Several other organizations, including the American Society of Clinical Oncology (ASCO) and the LIVESTRONG Foundation, in conjunction with Abramson Cancer Center, have also developed survivorship plan templates (here and here). And NCI plans to release a program announcement on the topic soon.

Although the process for developing an SCP goes fairly smoothly at Wayne HealthCare and doesn't require too much time, that's not the case at many cancer centers, explained Dr. McKellar. He should know. As the incoming chair of the American College of Surgeons (ACS) Commission on Cancer (CoC) and a surveyor for the CoC, he regularly visits ACS-accredited cancer centers.

SCPs are a hot topic during those meetings. In new standards released last year, the CoC announced that it would require all ACS-accredited facilities—where approximately 70 percent of newly diagnosed cancer patients in the United States are treated—to provide SCPs to all patients by 2015.

"We allowed for the 3-year phase-in period so we could better understand the barriers to, and develop best practices for, implementation," explained Dr. McKellar.

Bridging Multiple Divides

A critical—and, according to Stovall, understudied—component of a survivor's transition to post-treatment life is the handoff of routine care from the oncology clinic to the primary care office. Even if a cancer survivor's primary care physician receives the patient's SCP, for instance, there is no consensus on how the patient's subsequent care should be managed.

A study presented at the recent ASCO annual meeting, for example, found a substantial disconnect between oncologists' and primary care physicians' beliefs about survivorship care. Most oncologists surveyed in the study questioned primary care physicians' ability to provide the appropriate follow-up care and thought that oncologists were best equipped to provide such care. The majority of primary care physicians, on the other hand, felt most comfortable with a shared management approach in which they would care for patients alongside oncologists and their staffs.

And then there are the survivors like Kris Batley, who, regardless of whether they have an SCP, often aren't ready to depart the familiar folds of the oncology clinic.

"That is a key concern," said Dr. Eva Grunfeld of the University of Toronto, who has studied cancer survivorship for more than 20 years. Survivors "need reassurance that they are still part of the system and that if they need specialist care again, it will be available to them," she said.

The Next Research Wave

Dr. Grunfeld led the only randomized clinical trial to test an SCP's effects on survivors—in this case, women treated for early-stage breast cancer. In the trial, women who had an SCP did not have less cancer-related distress, the study's primary endpoint, than survivors who did not receive a plan.

Other clinical trials of SCPs are beginning to move forward. Dr. Stricker, for example, is leading a pilot trial to test the use of what she calls a "Cadillac" SCP that includes the information that wasn't captured in other plans. "This really is a comprehensive document that covers most, if not all, of the IOM-recommended content," she said.

A plan helps [survivors] know what's coming next, providing some predictability and order to their follow-up care.

—Ellen Stoval

And through its Grid-Enabled Measures initiative, NCI is supporting an effort to identify the most critical outcome measures to be used in SCP-related studies, such as quality of life, health care use, and costs.

Researchers in the field agree that progress is needed on many fronts. Payment reform, for instance, would ensure that cancer centers are reimbursed for preparing SCPs and reviewing the plans and the transition to survivorship with patients, Stovall noted. Advances in information technology, particularly the ability to link electronic medical records with SCPs, would make preparing SCPs much easier, Dr. Stricker said.

In addition, researchers need to test how best to develop, tailor, and implement SCPs and models of survivorship care to meet survivors' needs, explained Dr. Parry. The most appropriate transitional and follow-up care may differ depending on factors such as patients' age, their type and stage of cancer, the treatments they received, and the resulting degree and intensity of follow-up care needed, she continued.

Batley, who was treated at Abramson, received her SCP after meeting with a nurse practitioner in the center's Breast Cancer Survivorship Clinic to discuss post-treatment challenges. "It was great," Batley said. "We talked about things I never would have talked about with my oncologist, like anxiety and weight gain.

"I can understand why people are concerned about this issue," she continued. "There are so many more survivors now. And oncologists have only so many hours in a day."

Carmen Phillips

Further reading: "Passport for Care: An Internet-Based Survivorship Care Plan"

Featured Clinical Trial

Trastuzumab for Women with HER2-Low Breast Cancer

Name of the Trial
Phase III Randomized Study of Adjuvant Chemotherapy with versus without Trastuzumab in Women with Node-Positive or High-Risk Node-Negative HER2-Low Invasive Breast Cancer (NSABP-B-47). See the protocol summary.

Dr. Louis FehrenbacherDr. Louis Fehrenbacher

Principal Investigator
Dr. Louis Fehrenbacher, National Surgical Adjuvant Breast and Bowel Project (NSABP)

Why This Trial Is Important
Women with breast cancer that tests positive for HER2 overexpression have benefited greatly from the development of trastuzumab (Herceptin). Trastuzumab binds to HER2, a receptor protein found in abundance on some cancer cells, and either prevents it from transmitting growth signals to the cell nucleus or “tags” the cells for destruction by the immune system.

The Food and Drug Administration has approved trastuzumab for use with or without chemotherapy in women with HER2-positive metastatic breast cancer. The drug has also been approved for use as an adjuvant therapy in combination with chemotherapy for women with HER2-positive operable breast cancer. In several adjuvant therapy trials, adding trastuzumab to standard chemotherapy led to significant improvements in disease-free and overall survival.

When researchers involved in one of the trials (NSABP B-31) reanalyzed the results and re-examined tumor tissue from the participants in a central laboratory after the trial’s conclusion, they found that nearly 10 percent of the women in the study had breast cancer that should have been classified as HER2-negative or low because their tumors expressed less HER2 protein or had lower HER2 gene copy numbers than the threshold set to be classified as HER2 positive. However, women with these “HER2-negative/low” tumors that had previously tested positive seemed to experience the same benefit from trastuzumab as women whose tumors were “correctly” classified as HER2 positive. Subsequent analyses of available tissue confirmed that the tumors did not express high enough levels of HER2 protein or gene copy numbers to be considered positive and, therefore, eligible for trastuzumab therapy.

The HER2 status of tumor tissue is determined by two different methods: immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). IHC measures the level (0, 1+, 2+, or 3+) of HER2 protein expression on the surface of cancer cells, whereas FISH indicates whether the HER2 gene is amplified, meaning that the cancer cells have more copies of the gene than is normal. Currently, for breast cancer to be considered HER2 positive (and the patient to be eligible for trastuzumab), the cells must have an IHC expression score of 3+ or gene amplification must be detected.

Nonetheless, many women have breast tumors that are classified as HER2 negative yet still show some level of HER2 overexpression as measured by IHC (scores of 1+ or 2+). Researchers want to find out whether women with these “HER2-low” breast cancers will benefit from adjuvant trastuzumab as women with classically defined HER2-positive tumors do, as the NSABP B-31 study suggested.

In this clinical trial, women who have recently undergone surgical resection for HER2-low breast cancer and are at high risk for recurrence (because of spread of the cancer to the lymph nodes and/or tumor size) will undergo adjuvant chemotherapy and be randomly assigned to 1 year of trastuzumab treatment or no trastuzumab. Doctors will assess participants’ disease-free and overall survival, as well as the toxicity of the treatments.

“In a large breast cancer population, we find that only about 15 percent of patients [have tumors that] are HER2 amplified or 3+, while those [with tumors] that are HER2 1+ or 2+ may be as much as 45 percent to 50 percent of the population,” Dr. Fehrenbacher explained. “So, this is a study that we really should do because of the potential huge impact of a positive result on the breast cancer burden in the United States.”

For More Information
See the lists of entry criteria and trial contact information or call the NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.

Further reading: “Looking to Refine HER2-Targeted Therapy

An archive of "Featured Clinical Trial" columns is available at

Legislative Update

Congress Passes FDA User-Fee Legislation to Address Drug Shortages

Both chambers of Congress have passed the Food and Drug Administration (FDA) Safety and Innovation Act (S. 3187) to reauthorize the Prescription Drug User Fee Act and Medical Device User Fee and Modernization Act and create user fees to support the FDA review and inspection process for companies seeking approval for generic and biologically similar drugs. The House passed the bill on June 20, and the Senate followed suit on June 26.

The legislation requires drug manufacturers to provide advance notice 6 months before the production of a drug is interrupted or discontinued, or as soon as practical. The bill allows for expedited review of abbreviated new drug applications (or supplements) when these measures can help to mitigate or prevent shortages, as well as expedited inspection or re-inspection of a production facility that could help mitigate or prevent shortages. The bill also calls for more coordination between the FDA and the attorney general regarding drugs subject to quotas under the Controlled Substances Act

The administration released a Statement of Administration Policy on May 17 in support of the Senate proposal, and President Barack Obama is expected to sign the bill into law. The statement specifically mentions the proposal’s provisions to prevent and mitigate drug shortages. (See “Continued Shortage of Chemotherapy Drugs Causing Concern.”) 

In addition, the bill addresses issues related to clinical research and drug and device development. The legislation reauthorizes the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act, and includes

  • language providing for expedited development and review of drugs that show an effect early in development for serious or life-threatening diseases ("breakthrough" therapies);
  • provisions regarding global clinical trials that encourage uniform, scientifically driven clinical trial standards for medical products; 
  • reauthorization of the Orphan Products Grants Program; and
  • authorization of priority review for treatments for rare pediatric diseases.

More information about the bill, including details about the drug shortage provisions, is available online from NCI's Office of Government and Congressional Relations.

Holly Gibbons Update

Blog Aims to Stimulate Fresh Thinking on Cancer Epidemiology

To engage a broad audience in charting the direction of cancer epidemiology in the 21st century, NCI’s Epidemiology and Genomics Research Program (EGRP) recently launched a new blog, “Cancer Epidemiology Matters.”

Collage of words used in the titles of EGRP grants.

The blog aims to engage EGRP’s stakeholders, including researchers, clinicians, community partners, advocates, and other people with an interest in cancer epidemiology and genomics, in discussions on practices, priorities, findings, and trends in epidemiologic research and how they can be used to reduce the global burden of cancer.

Responding to recent scientific advances and changes in NCI’s funding environment, EGRP’s blog seeks to confront challenges and to identify the greatest opportunities for cancer epidemiology to make a difference over the next decade in research, policy, and translation to clinical practice. Seeking input from its stakeholders, EGRP hopes to inform the future of cancer epidemiology and to speed the generation and application of knowledge about determinants of cancer occurrence and population outcomes.

EGRP staff and invited guests will post discussions every few weeks on various cancer epidemiology research topics. Readers’ suggestions and input are welcome. Please post a comment or a question.

To receive blog updates, sign up for the blog’s RSS feeds for posts and comments and/or subscribe to EGRP’s listserv. Suggestions for future discussions can also be submitted to EGRP’s blog team at


NCI Advisory Boards Hold Joint Meeting This Week

NCI’s Board of Scientific Advisors (BSA) and the National Cancer Advisory Board (NCAB) held a joint meeting June 24–25 on the NIH campus in Bethesda, MD.

Drs. Harold Varmus, Doug Lowy, and James Doroshow opened the meeting with the NCI Director’s Report. Their presentation included a discussion on NCI’s Provocative Questions Project, as well as the absolute risk reduction in the National Lung Screening Trial (NLST). (See the NLST Patient and Physician Guide.)

Attendees then heard presentations on a number of topics, including a report on the President’s Cancer Panel, the Frederick National Laboratory for Cancer Research strategic plan, highlights of efforts to improve the efficiency of NCI-sponsored clinical trials, and an update on the National Cancer Informatics Program.

The board members also recognized several departing BSA and NCAB members.

The agenda is available online, and an archived videocast of the meeting will be posted in a few days.

William Dahut Named Deputy Director of NCI's Center for Cancer Research

Dr. William Dahut has been named deputy director of NCI’s Center for Cancer Research (CCR). In this role, he will provide administrative and scientific oversight to a group of CCR laboratories and branches. He will also advise the CCR director and scientific director for clinical research on strategy, priority setting, resource allocation, and policy development.

Dr. William DahutDr. William Dahut

After joining NCI’s Medicine Branch in 1998 as head of the prostate cancer clinic, Dr. Dahut later became chief of the Genitourinary/Gynecological Clinical Research Section in what is now the Medical Oncology Branch.

Dr. Dahut will continue his role as clinical director of CCR, a position he has filled since 2009. In that role, Dr. Dahut oversees CCR’s clinical operations, including patient recruitment, clinical protocol review, management of inpatient units and outpatient clinics, human subjects protection, quality of patient care, and data management support.

Dr. Dahut’s primary research interest is the development of novel treatments for adenocarcinoma of the prostate.

Research to Reality Cyber-Seminar: How to Measure Health Disparities

The July 10 NCI Research to Reality (R2R) cyber-seminar will explore efforts and tools to help researchers and practitioners monitor and evaluate community health disparities. The seminar will highlight the Health Disparities Calculator (HD*Calc), free statistical software from NCI designed to evaluate and monitor health disparities.

Drs. Nancy Breen and Eva Wong Drs. Nancy Breen and Eva Wong

Dr. Nancy Breen of NCI’s Health Services and Economics Branch and her colleagues will provide an overview and demonstration of the tool. Dr. Eva Wong of the Seattle and King County (WA) Department of Public Health will discuss how Seattle/King staff have used the tool to evaluate health disparities in their county and how it has helped them improve programs designed to address these disparities.

For more information and to register for this event, visit the R2R website, where you can watch presentations and join discussions. All R2R cyber-seminars are archived on the website a week after the presentation. 

For more information on the cyber-seminar series, please e-mail

NCI Community Health Expo Will Feature Genomics, Biospecimens Research

NCI’s Center to Reduce Cancer Health Disparities and Center for Cancer Genomics, in conjunction with several NCI-designated cancer centers and other national and community organizations, will hold a community health expo, “Our Families, Our Research, Our Future,” on Saturday, July 14, from 10:00 a.m. to 3:00 p.m. ET at the Civic Building in Silver Spring, MD.

The free event is open to the public and will feature a variety of interactive exhibits on healthy lifestyles, preventive cancer screening, and research.

Community Health Expo 2012 banner

A panel of researchers will discuss community participation in biospecimen and clinical research from 11:30 a.m. to 12:15 p.m. ET. The discussion will include an introduction to tissue donation and explain why biospecimens are important in cancer research, what happens to donated tissue, the benefits and risks involved in research participation, and how high-quality biospecimens help researchers reduce cancer health disparities.

Attendees will also have an opportunity to participate in hands-on activities that demonstrate basic concepts of genome analysis and illustrate how genomics can reduce the burden of cancer.

More information about the event is available online.