National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
October 16, 2012 • Volume 9 / Number 20

NEWS

Treatment Options for HER2-Positive Breast Cancer Expand and Evolve

New results from three clinical trials highlight the evolving treatment options for women who have HER2-positive breast cancer. These cancers, which produce too much HER2 receptor protein, are a particularly aggressive form of the disease and account for approximately 20 percent of all breast cancer diagnoses. 

In one trial, researchers showed that the investigational drug T-DM1 improved overall survival in women with advanced HER2-positive disease who had been previously treated with the HER2-targeted drug trastuzumab (Herceptin) and taxane chemotherapy. These updated findings from the EMILIA trial appeared October 1 in the New England Journal of Medicine. Read more > >

IN DEPTH

UPDATES

  • Notes

    • Director's Consumer Liaison Group to Meet Next Week
    • Meet NCI Experts at the American Public Health Association Annual Meeting
    • NCI Reaches Facebook Milestone

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.

For more information about cancer, call 1-800-4-CANCER or visit http://www.cancer.gov.

NCI Cancer Bulletin staff can be reached at ncicancerbulletin@mail.nih.gov.

Featured Article

Treatment Options for HER2-Positive Breast Cancer Expand and Evolve

Directional sign with arrows labeled good, better, and best
Researchers are looking for better treatment options for women with HER2-positive breast cancer.

New results from three clinical trials highlight the evolving treatment options for women who have HER2-positive breast cancer. These cancers, which produce too much HER2 receptor protein, are a particularly aggressive form of the disease and account for approximately 20 percent of all breast cancer diagnoses.

In one trial, researchers showed that the investigational drug T-DM1 improved overall survival in women with advanced HER2-positive disease who had been previously treated with the HER2-targeted drug trastuzumab (Herceptin) and taxane chemotherapy. These updated findings from the EMILIA trial appeared October 1 in the New England Journal of Medicine.

“Only a few studies in metastatic breast cancer have shown an improvement in overall survival. It’s tough to do,” said the trial’s lead investigator, Dr. Sunil Verma of the Sunnybrook Odette Cancer Centre in Toronto. “The gain that we saw in this trial, an incremental improvement of 5.8 months, is one of the largest seen of any trial reported to date [in this disease]. And we’re seeing that gain with less toxicity.”

In addition, findings from two other clinical trials, presented at the European Society for Medical Oncology Congress (ESMO), provided more evidence that the existing duration of adjuvant treatment with trastuzumab in women with early-stage breast cancer should remain 1 year.

The trials are part of what has become an increasingly dynamic area of research for HER2-positive breast cancer.

The Food and Drug Administration (FDA), for example, recently approved pertuzumab (Perjeta), which also targets the HER2 receptor, in combination with trastuzumab and docetaxel for women with metastatic HER2-positive breast cancer. And T-DM1 is already being tested in a phase III trial as a first-line therapy for these women.

Researchers are also testing several investigational drugs that disrupt signaling pathways thought to play an important role in tumor resistance to HER2-targeted agents, said Dr. Ingrid Mayer, clinical core director of the Breast Cancer Program at Vanderbilt-Ingram Cancer Center in Tennessee.

“It is possible that, with so many active drugs against HER2-positive disease, we may eventually see some patients with stage IV disease being cured,” Dr. Mayer said. But, she cautioned, much more research is needed before this would be possible.

In Advanced Disease, Improving Overall Survival

In the nearly 1,000-patient EMILIA trial, women who received T-DM1 had substantially better overall survival than women treated with the chemotherapy agent capecitabine (Xeloda) and another HER2-targeted drug, lapatinib (Tykerb): 30.9 months versus 25.1 months. (As previously reported, women who received T-DM1 also had better progression-free survival: 9.6 months versus 6.4 months.)

The gain that we saw in [the EMILIA trial] is one of the largest seen of any trial reported to date [in this disease]. And we're seeing that gain with less toxicity.

—Dr. Sunil Verma

T-DM1 is an antibody-drug conjugate that combines the monoclonal antibody trastuzumab and the chemotherapy drug DM1.

Trastuzumab has been linked to cardiovascular complications, but the two treatment groups had similar rates of cardiac events. Dr. Verma stressed, however, that clinicians should be cautious in interpreting the safety findings because patients who experienced cardiac toxicity with trastuzumab were not eligible for the trial, so those at increased risk for such complications were “selected out.”

“We still need to do more studies, but T-DM1 doesn’t appear to be any worse than capecitabine and lapatinib in terms of cardiac toxicity,” Dr. Verma said.

Genentech, which markets T-DM1 in the United States, has submitted a biologics license application to the FDA to market the drug for women with locally advanced or metastatic HER2-positive breast cancer that cannot be treated with surgery and who previously received trastuzumab and taxane chemotherapy.

In Early-Stage Disease, Finding the Optimal Treatment Duration

For now, at least, the standard of care for women with early-stage HER2-positive breast cancer should remain 1 year of adjuvant trastuzumab. That was the conclusion reached by the researchers who led the HERA and PHARE trials, which tested different durations of adjuvant treatment. Updated results from both trials were presented at ESMO earlier this month.

The 5,000-patient HERA trial had three treatment groups: 2 years of adjuvant treatment with trastuzumab, 1 year of trastuzumab, or observation. After a median follow-up of more than 8 years, progression-free and overall survival were nearly identical in the 1-year and 2-year treatment groups, Dr. Richard Gelber of the Dana-Farber Cancer Institute reported.

Over time, the difference in progression-free survival between participants who received trastuzumab for 1 year and those who underwent observation narrowed. Even with the longer follow-up, however, women who received 1 year of trastuzumab lived 24 percent longer without their disease progressing.

“We know that this...is an underestimate of the effect of the treatment, because more than half of patients in the placebo arm actually received trastuzumab later on,” Dr. Gelber said during a press briefing.

Although the rates of cardiac-related death and congestive heart failure were less than 1 percent in both treatment groups, women who received trastuzumab for 2 years had a statistically significantly higher incidence of reduced heart function (left ventricular ejection fraction), he reported.

For now, at least, the standard of care for women with early-stage HER2-positive breast cancer should remain 1 year of adjuvant trastuzumab. That was the conclusion reached by the researchers who led the HERA and PHARE trials.

The PHARE trial, meanwhile, compared 12 versus 6 months of adjuvant treatment with trastuzumab in the same patient population. The trial was smaller (3,380 patients), and it was a noninferiority trial. Noninferiority trials aim to demonstrate that the effectiveness of one treatment is not less than that of another treatment by more than a predetermined margin, suggesting that they are essentially equivalent.

Based on about 3.5 years of follow-up, the results “are inconclusive for noninferiority” between 6 and 12 months of adjuvant trastuzumab, explained the trial’s lead investigator, Dr. Xavier Pivot of Université de Franche-Comté, at an ESMO press briefing. There was, however, “a strong trend in favor of 12 months of treatment,” Dr. Pivot said.

The shorter treatment duration appeared to be safer, Dr. Pivot noted, with the percentage of women experiencing cardiac events nearly three times as high in women who received trastuzumab for 1 year (5.7 percent versus 1.9 percent). In the trial, however, “‘cardiac event’ was a composite variable” encompassing several heart-related problems, he explained, “so interpreting these data is not so easy.”

Based on the results thus far, Dr. Mayer agreed, the standard of care for adjuvant treatment with trastuzumab in women with early-stage HER2-positive breast cancer should remain 1 year.

Although he concurred, Dr. Gelber stressed that the follow-up was not long enough to draw any definitive conclusions.

“There are some patients who may do just as well with the shorter duration,” Dr. Gelber said.

The most recent analysis of patient subgroups in the PHARE trial will be presented in December at the San Antonio Breast Cancer Symposium. These findings may begin to identify women who need only 6 months of adjuvant trastuzumab, Dr. Pivot said.

Several other international clinical trials are testing shorter durations of adjuvant trastuzumab treatment in women with early-stage HER2-positive breast cancer.

Carmen Phillips

Further reading: “For Some Breast Cancers, New Drug May Be Treatment Option” and “Pertuzumab Approved to Treat Some Metastatic Breast Cancers

Cancer Research Highlights

Adding Chemotherapy to Radiation Improves Survival for Some Patients with Rare Brain Cancer

Long-term follow-up results from two clinical trials confirm that certain patients with anaplastic oligodendrogliomas, which account for less than 10 percent of brain and central nervous system cancers, live substantially longer if they are treated with a combination of chemotherapy and radiation therapy rather than radiation alone.

In the trials—both of which were launched in the mid-1990s—patients whose tumor cells had missing or deleted parts of chromosomes 1 and 19 and who received the combination treatment lived substantially longer than patients whose tumors had these deletions but who received radiation therapy alone. About half of patients diagnosed with anaplastic oligodendroglioma have these chromosomal co-deletions. The combination treatment did not improve survival for patients whose tumor cells lacked the deletions.

Because of the immediate implications for patients, NCI and the Radiation Therapy Oncology Group (RTOG) announced the results of one of the trials, RTOG 9402, in January before they had been published or presented at a medical conference. Findings from both studies were presented in June at the American Society of Clinical Oncology annual meeting and published online October 15 in the Journal of Clinical Oncology.

“These studies establish a new standard of care for patients with [anaplastic oligodendroglioma] tumors that harbor the 1p19q loss. No longer is radiation considered an adequate treatment for this patient population,” wrote Dr. Mark Gilbert of the University of Texas MD Anderson Cancer Center in an accompanying editorial.

In the NCI-funded RTOG trial, participants whose tumors harbored both chromosomal deletions and who received high-dose chemotherapy with procarbazine (Matulane), lomustine (CeeNu), and vincristine (Vincasar), a regimen known as PCV, followed by radiation had a median survival of 14.7 years. Participants with the deletions who received radiation alone had a median survival of 7.3 years. 

Median survival for patients whose tumors did not have the chromosomal deletions was less than 3 years, regardless of whether they received the combination therapy or radiation alone.

In the other trial, EORTC 26951, patients received radiation therapy alone or radiation followed by a standard-dose PCV regimen. The median overall survival cannot yet be calculated for patients with the chromosomal co-deletions who received the combination therapy, but there is a strong trend toward improved overall survival.

There is still some uncertainty about the preferred treatment for these patients, cautioned the RTOG trial’s principal investigator, Dr. Gregory Cairncross of the University of Calgary and his colleagues. For example, because it can improve survival in glioblastoma, has fewer side effects, and is easier to administer than the PCV regimen, many oncologists appear to prefer using temozolomide (Temodar) to treat anaplastic oligodendroglioma.

In January, enrollment was suspended for a clinical trial called CODEL that was to include only patients with 1p19q deletions and randomly assign them to radiation alone or radiation plus chemotherapy with temozolomide. Because the evidence so strongly supports the combination of chemotherapy and radiation for patients with the chromosomal deletions, a radiation-alone arm would be unethical, trial leaders explained.

According to Dr. Bhupinder Mann of NCI’s Division of Cancer Treatment and Diagnosis, the trial is being redesigned, with the hope of finalizing the changes by the end of the year.

RTOG 9402 was supported by grants from the National Institutes of Health (U10 CA21661, U10 CA32115, U10 CA25224, CA17145, CA21115, CA32102, and U10 CA37422).

Further reading: “Genetic Abnormality Predicts Treatment Benefit for Patients with Rare Brain Tumor

HIV Linked to Rising Rates of Anal Cancer among U.S. Men

An increase in the incidence of anal cancer among men in the United States during recent decades may have been driven in part by the HIV epidemic that occurred during the same period, a new study suggests. The results, published in the Journal of the National Cancer Institute on October 4, provide a framework for understanding the rising rates of anal cancer in men and could help guide efforts to prevent the disease.

Dr. Meredith S. Shiels of NCI’s Division of Cancer Epidemiology and Genetics and her colleagues estimated that between 2001 and 2005, more than 28 percent of anal cancer cases among men were associated with HIV infection, whereas only 1.2 percent of anal cancer cases in women were associated with HIV.

Although anal cancer is rare in the United States, the incidence has been increasing since 1940. Between 1980 and 2005, the rate of anal cancer in men in the general population rose 3.4 percent per year. The authors noted that half of this increase was due to cases of anal cancer occurring in men who were infected with HIV.

Men who have sex with men are at high risk of both HIV infection and anal cancer. Human papillomavirus (HPV) infections of anal tissue and anal precancerous lesions, which increase the risk of anal cancer, are common in this group. But the extent to which the incidence of anal cancer among people infected with HIV has affected incidence rates in the general population was not clear.

To explore this question, the study authors used data from the HIV/AIDS Cancer Match Study. They looked at the number of people with anal cancer infected with HIV in 17 U.S. states and metropolitan areas.

“HIV-infected cases have had a substantial impact on trends in anal cancer rates among men in the U.S.,” said Dr. Shiels. She noted that rates among women have also increased, but the cause remains unclear. “Efforts to reduce the risk of anal cancer in HIV-infected men could have a sizeable impact on anal cancer rates at the general population level,” she concluded.

This research was supported in part by NCI's Intramural Research Program.

Further reading: "HPV Vaccine Study in Costa Rica Yields Insights on Cancer Prevention"

HIV Drug Blocks Growth of HER2-Positive Breast Cancer Cells

Nelfinavir, a drug used to treat people infected with HIV, appears to halt the growth of HER2-positive breast cancer cells. Researchers led by Dr. Joong Sup Shim of the Johns Hopkins School of Medicine showed that, in the laboratory, doses of nelfinavir used to safely treat people infected with HIV inhibited the growth of drug-resistant HER2-positive breast cancer cells. The study appeared October 5 in the Journal of the National Cancer Institute.

Although several drugs are approved to treat HER2-positive breast cancers, tumors often develop resistance to these drugs, and new treatments are needed.

The researchers exposed seven genetically characterized breast cancer cell lines to drugs cataloged in the Johns Hopkins Drug Library, including anticancer drugs and drugs used to treat other diseases. (The protein-coding genes in the cells had been sequenced to determine whether they had mutations known to drive cancer.)

After finding that nelfinavir selectively inhibited HER2-positive breast cancer cells, compared with HER2-negative cells, the researchers teased out how the drug might work in HER2-positive cells. They found that nelfinavir inhibits a protein called heat-shock protein 90 (HSP90). Heat-shock proteins act as “chaperones,” helping newly synthesized proteins to fold properly and stabilizing their structures. When the activity of HSP90 is blocked by nelfinavir, the proteins that it normally helps fold and stabilize may not work correctly.

HSP90 helps stabilize the HER2 protein and another protein in its signaling pathway called AKT. Therefore, blocking HSP90 activity may lead to the breakdown of HER2 and AKT or a decrease in their activity, explained the authors. This could slow or stop the growth of cancer cells that cannot function without abnormal HER2 signaling.

When the researchers tested nelfinavir in xenograft models of breast cancer, mice with HER2-positive tumors that were given nelfinavir had tumors less than half the size of those in mice that were not given the drug, and nelfinavir substantially reduced the levels of active HER2 (but not AKT) in the tumors. In cell-culture experiments, nelfinavir inhibited the growth of three HER2-positive cell lines that were resistant to the anti-HER2 drugs trastuzumab (Herceptin) or lapatinib (Tykerb).

The researchers hope that clinical trials will start soon. The rationale for clinical trials of nelfinavir is particularly strong for patients with resistance to the available anti-HER2 treatments, who have a poor prognosis, explained Dr. Jun O. Liu, the study’s senior author.

The advantage of using a drug already approved for another disease, he added, is that the drug can likely skip phase I trials and go straight into phase II trials if tested at a dose currently used in the clinic. Another drug the research team found using this screening process, an antifungal/antibiotic called itraconazole, which inhibits tumor blood-vessel formation, leapt directly into phase II testing in cancer patients, he noted. (See the trial details here, here, and here.)

This research was supported by grants from the National Institutes of Health (CA122814, R01AI065983, and UL1 RR 025005).

Exercise, Behavioral Therapy Reduce Menopausal Symptoms Caused by Breast Cancer Treatment

Women with breast cancer who were suffering from treatment-related menopausal symptoms experienced symptom relief with cognitive behavioral therapy, physical exercise, or both, according to a Dutch study. The findings were published October 8 in the Journal of Clinical Oncology.

Dr. Neil K. Aaronson of the Netherlands Cancer Institute and his colleagues randomly assigned 422 patients to behavioral therapy, physical activity, an intervention combining the two, or a control group that received usual care. The purpose of the study was to evaluate the effects of psychosocial interventions and exercise on menopausal symptoms, such as hot flashes and night sweats, as well as on sexual functioning, psychological well-being, and health-related quality of life. The patients reported their symptoms at the start of the study and 12 weeks and 6 months later.

Compared with the control group, women who received the interventions had statistically significantly lower levels of endocrine and urinary symptoms, and behavioral therapy and physical activity had a positive effect on physical functioning. The researchers noted, however, that physical activity “affects primarily the frequency with which endocrine symptoms are experienced, but not the frequency of hot flashes and night sweats specifically.” Cognitive behavioral therapy, in contrast, “seems to not only affect symptom frequency, but also the perceived burden of hot flashes and night sweats.”

In a related editorial, Mayo Clinic researchers Drs. Debra Barton and Charles Loprinzi commented that, despite its limitations, the study demonstrated that “it is not sufficient to consider only biomedical influences [on symptoms]. …For complete symptom resolution, it may be necessary to address both the physiological expression and psychosocial context of the symptom.”


Also in the Journals: Study Compares Screening Methods for Lynch Syndrome

A large, population-based, international study found that routine screening of colorectal tumors for DNA mismatch repair (MMR) genes was more sensitive than several other screening methods for identifying patients with Lynch syndrome. The researchers compared tumor MMR testing with three other screening strategies: the Bethesda guidelines, the Jerusalem recommendations, and another strategy based on an analysis of variables associated with Lynch syndrome. Their findings were published in JAMA today.

Although MMR testing offered only a “modest” diagnostic improvement, up to 15 percent of people with Lynch syndrome could remain undiagnosed without routine screening of colorectal tumors. And, identifying those with Lynch syndrome is critical to diagnosing relatives before they develop symptoms, so they can take preventive measures to decrease their risk of disease and death, explained the authors.

This research was supported by grants from the National Institutes of Health (CA67941 and CA16058).

Further reading: “Routine Lynch Syndrome Screening Varies at U.S. Cancer Centers

Special Report

New Biomarker May Allow Earlier Diagnosis of Mesothelioma

CT scan of the chest showing a malignant mesothelioma circled in red (Image by Dr. Tomas Dvorak, MD Anderson Cancer Center Orlando)
CT scan of the chest showing a malignant mesothelioma (Image by Dr. Tomas Dvorak, MD Anderson Cancer Center Orlando)

Researchers have shown that the protein fibulin-3 may be able to distinguish patients with mesothelioma from people with similar conditions and from healthy individuals. Although preliminary, the results suggest that this protein may be a promising new biomarker for diagnosing the disease and possibly informing prognosis. The study was published October 11 in the New England Journal of Medicine.

Pleural mesothelioma, a disease of the tissue that lines the chest cavity and covers the lungs (the pleura), is an aggressive cancer often associated with asbestos exposure. Patients diagnosed with this disease have a median survival of 1 year.

Diagnosing mesothelioma early, when treatment may be most effective, is difficult because of its long latency period and the lack of reliable methods to detect the disease in its early stages. A protein called soluble mesothelin-related protein is the best-studied biomarker for mesothelioma, but the test for it has low sensitivity, meaning that it fails to detect mesothelioma in some people who have the disease.

In the study, supported by NCI’s Early Detection Research Network (EDRN), Dr. Harvey Pass of the New York University Langone Medical Center and his colleagues identified fibulin-3, a protein important in cell-to-cell and cell-to-extracellular matrix signaling, as a potential mesothelioma marker.

The researchers measured fibulin-3 levels in plasma and pleural effusion samples from 142 patients with mesothelioma, 136 cancer-free individuals exposed to asbestos, and 93 patients with effusions not due to mesothelioma. The researchers also evaluated plasma samples from 91 patients with cancers other than mesothelioma and 43 healthy control subjects. Many of these samples came from EDRN.

Average plasma fibulin-3 levels were higher in patients with mesothelioma than in people without cancer who had been exposed to asbestos. Patients with mesothelioma and those without the disease could be distinguished with a sensitivity of 96.7 percent and a specificity of 95.5 percent at a cutoff level of 52.8ng/ml of plasma fibulin-3.

The researchers used another cohort of plasma samples to validate their findings, though the sensitivity and specificity fell to 72.9 percent and 88.5 percent, respectively.  

“This is a totally new marker; something that we have never thought about in mesothelioma,” commented Dr. Raffit Hassan of NCI’s Center for Cancer Research, who was not involved in the study. “Fibulin-3 appears to be much better than serum mesothelin in terms of sensitivity and specificity.”

Plasma fibulin-3 levels may also be helpful in monitoring response to therapy and disease progression. In 18 patients, fibulin-3 levels fell after surgery, and there was a trend toward rising fibulin-3 at the time of disease progression in 6 of these patients.

Fibulin-3 levels were higher in effusion samples than in plasma samples. In the few patients with both plasma and effusion samples, there was no clear relationship between the fibulin-3 levels in the two locations. Effusion fibulin-3 levels, however, were able to distinguish patients with mesothelioma from those with effusions not related to the disease, a welcome finding as it is difficult to distinguish patients with mesothelioma from those with benign effusions or malignant effusions due to other cancer types.

Likewise, effusion fibulin-3 levels were lower in patients with stage I or II mesothelioma than in those with stage III or IV disease. Patients with the highest effusion fibulin-3 levels at the time of surgery had shorter survival times.

The results are promising, though more studies involving a larger number of patients and prospective studies are needed to validate fibulin-3 as a biomarker for mesothelioma, noted Dr. Hassan.

“The other important thing would be to see if the levels of fibulin-3 could be used as a biomarker for response to chemotherapy or other biological therapies,” he said. “Since mesothelioma is a very difficult disease to measure radiologically, it would be nice to have a sensitive and specific assay for monitoring response to treatment.”

Jennifer Crawford

This research was supported by grants from the National Institutes of Health (U01 CA-111295 and U01 CA-113913).

Featured Clinical Trial

Comparing Relaxation Programs for Breast Cancer Patients Receiving Radiotherapy

Name of the Trial
Biobehavioral Effects of Relaxation for Women with Breast Cancer Undergoing Radiotherapy (2009-0976; NCT01202851). See the protocol summary.

Dr. Lorenzo Cohen
Dr. Lorenzo Cohen

Principal Investigator
Dr. Lorenzo Cohen, University of Texas MD Anderson Cancer Center

Why This Trial Is Important
Women with early-stage breast cancer usually have surgery to remove the tumor followed by radiation therapy. Depending on the characteristics of their cancer, they may also receive systemic therapies, including chemotherapy, hormonal therapy, targeted therapy, or a combination of these, before and/or after surgery. This multimodality treatment has helped many women survive breast cancer, but the rigors of treatment can leave women with other problems that may affect their health and sense of well-being.

Breast cancer surgery can result in lingering pain and affect physical functioning and range of body movement. Systemic therapies can cause sleep disruption, reduced ability to concentrate and to remember, fatigue, peripheral neuropathy, and other complications, whereas radiation therapy may cause fatigue, tenderness or swelling in the treated area, and, in some cases, peripheral neuropathy. These side effects can greatly affect a person’s quality of life and cause stress, which may exacerbate a negative sense of well-being.

Radiation therapy following breast cancer surgery typically involves daily treatments for 4 to 6 weeks. Some doctors believe that this daily contact with patients may be an opportunity to teach them methods to reduce the severity of cancer symptoms and treatment side effects, as well as associated stress.

In this study, women with breast cancer who have had surgery and are scheduled to undergo radiation therapy will be randomly assigned to one of two different stretching and relaxation programs or to a control group that will receive usual care. Both active arms of the study will include stretching exercises, breathing exercises, and relaxation exercises. Women assigned to either of the relaxation programs will participate in 3 to 5 sessions a week for the duration of their radiation therapy and will then be asked to practice the relaxation techniques on their own every day for the following year.

All participants will complete questionnaires and 7-day sleep diaries before radiation therapy begins, midway through their radiation treatment, and during their last week of therapy, as well as at 3, 6, and 12 months after radiation treatment ends. Additionally, they will submit saliva samples before radiation therapy begins, during the last week of therapy, and at 3, 6, and 12 months after radiation treatment ends. The tests will measure levels of cortisol, a chemical in the body associated with stress, in their saliva at these different time points.

“We’ve seen from our previous research that women who participate in these types of programs throughout treatment have improvement in aspects of physical functioning and their ability to engage in daily activities,” said Dr. Cohen.

“One particularly interesting aspect of the study is that we are measuring cortisol as an indicator of stress. We know that cortisol levels vary throughout the day, usually higher in the morning and tapering off over the course of the day, and there’s evidence that a greater slope of this diurnal cortisol change is associated with better survival in patients with metastatic breast cancer. Our research indicates that women who practice mind-body relaxation programs, like yoga, tend to have steeper cortisol slopes.

“Another very important element of the study will be cost/benefit analyses between the women in each arm of the study, particularly in terms of documenting work productivity and functioning,” he explained. “We’re interested not only in whether women go to work or not, but also the degree to which they are able to focus on and be engaged in their work tasks, either outside or inside the home.”

The study is taking place at the University of Texas MD Anderson Cancer Center in Houston.

For More Information
See the lists of eligibility 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.

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

Community Update

Basser Research Center: Focusing on BRCA-Related Cancers

Cancer Centers iconThe recently opened Basser Research Center for BRCA has a unique mission. As the name suggests, the center focuses solely on BRCA-related cancers, from basic research to clinical treatment. Located at the NCI-designated Abramson Cancer Center at the University of Pennsylvania (Penn) in Philadelphia, the center was funded with an initial donation of $25 million from Mindy and Jon Gray in honor of Mindy’s sister, Faith Basser, who died of ovarian cancer at the age of 44.

Dr. Susan Domchek, executive director of the Basser Research Center (Courtesy of Penn Medicine)
Dr. Susan Domchek hopes that research done at the Basser Research Center will eventually provide better options for people with BRCA mutations. (Courtesy of Penn Medicine)

People with BRCA gene mutations are at higher risk than the general population for developing several kinds of cancer, particularly breast and ovarian cancer. (See the box below.) Researchers at the Basser Center aim to develop ways to prevent BRCA-related cancers or detect them early. And investigators at the new center believe much of the research will have broader implications.

“What we will learn about BRCA1/2 in terms of risk, prevention, detection, and therapeutics can be applied not only to other forms of breast and ovarian cancers, but to other cancers as well,” said Dr. Susan Domchek, executive director of the center. “This is about understanding how cancers develop in these individuals, and, therefore, how we can target them.”

Breadth and Depth

One of the Basser Research Center’s strengths is that it draws on Penn’s clinical and research resources. For example, women with breast and gynecologic cancers receive treatment at facilities that specialize in those cancers and genetic counseling at a center that specializes in evaluating risk for women’s cancers. On the research side, the Basser Center draws on ovarian and breast cancer research programs, a translational research program, a center for personalized diagnostics, and a cell and vaccine production facility.

“The important thing is that this center has breadth and depth,” said Dr. Domchek. “The basic biology is as important as how a woman can talk to her 14-year-old about why she is having a bilateral mastectomy.”

By bringing together experts in immunotherapy, cancer genetics, molecular imaging, epidemiology, statistics, basic science, and clinical care, the Basser Research Center hopes to spur innovation, according to Dr. Chi Van Dang, director of the Abramson Cancer Center, which is funded in part by NCI.  

“We have monthly meetings where all investigators present their work, and it really allows us to feed off each other,” explained Dr. Domchek. Especially valuable, she noted, is that clinicians and basic scientists interact regularly, allowing clinicians to bring their questions directly to the scientists.

Many of the researchers have worked together before, Dr. Dang noted, but the creation of the center is really a “superglue” that brings people together.

Delving Deeper

The funding infusion from the Gray family has allowed researchers to dive more deeply into existing research areas. For example, Penn has a tumor tissue and biospecimen bank, and the new funding will help establish a section of the biobank for serum and plasma specimens, which will be used to develop and test biomarkers.

What we will learn about BRCA 1/2 in terms of risk, prevention, detection, and therapeutics can be applied not only to other forms of breast and ovarian cancers, but to other cancers as well.

—Dr. Susan Domchek

“Early detection aided by biomarkers or imaging is incredibly important for us,” stressed Dr. Domchek. Currently, no effective screening method exists for ovarian cancer, and the most common method of prevention is removal of the ovaries, sometimes at a relatively young age. And many women who have BRCA1/2 mutations also have a bilateral mastectomy to reduce their risk of developing breast cancer.

The funding has also enabled Basser researchers to delve into other new areas, such as new imaging capabilities and immune-based treatment strategies.

“Some of our researchers are studying specific molecular targets that will allow us to develop imaging agents [for] early detection of disease,” explained Dr. Dang. “On the flip side, the same [molecules] might be targeted directly with immune cells that we can engineer. Ultimately, we want to develop vaccines and imaging techniques that will allow women [to forgo] those surgeries in the future,” he said.

Although the proteins produced by BRCA1/2 are known to play a critical role in repairing damaged DNA, scientists do not yet fully understand how BRCA mutations can cause cancer or why mutations in certain regions of the genes appear to raise the risk of developing ovarian cancer rather than breast cancer, said Dr. Dang. Such an understanding would help researchers find ways to prevent and treat these cancers, noted Dr. Domchek.

When to Test?

Dr. Chi Van Dang, director of the Abramson Cancer Center (Courtesy of Penn Medicine)
Dr. Chi Van Dang believes that research being done at the Basser Center may lead to better imaging techniques and immunotherapies. (Courtesy of Penn Medicine)

The Basser Research Center is also using funds from the Gray's donation to improve outreach, education, and collaboration. This includes partnering with an organization called Facing Our Risk of Cancer Empowered (FORCE), an advocacy and support group for people affected by hereditary breast and ovarian cancer. The center has also created a webpage where people can request clinical or research information about BRCA-related cancers and has hired more genetic counselors who can help people find local resources or join a clinical trial.

Just the process of testing for BRCA mutations is fraught with difficult questions, Dr. Dang noted.

“At what age do you test, when do you inform patients of the results, what is the impact of those results, and how might the results affect the individual’s psychological outcome,” he said. “This research is not molecularly based, but it’s extremely important for the mental and physical health of individuals.”

In part because the Basser Center is spurring collaboration and innovation, and allowing researchers to dig more deeply into their projects, he hopes the findings will come more quickly. “Instead of coming out in 3 to 5 years, we’ll be seeing information in a shorter timeframe,” he predicted.

The funding will allow Basser researchers to do many new things, but “the most important thing that I’ve seen to date is that [the new center] really brings hope to people with these mutations,” said Dr. Dang.

—Virginia Hulme

As an NCI-designated comprehensive cancer center, the Abramson Cancer Center is funded in part by a Cancer Center Support Grant (P30CA016520).

Further reading: “BRCA1 and BRCA2: Cancer Risk and Genetic Testing

BRCA1 and BRCA2

When BRCA1 and BRCA2 work normally, the proteins they produce suppress tumor formation by helping to prevent uncontrolled cell growth. Sometimes, however, these genes contain harmful mutations that increase the risk of certain cancers. Women with mutations in BRCA1 or BRCA2 have greater risks of breast and ovarian cancers, as well as cervical, uterine, pancreatic, colon, stomach, gallbladder and bile duct cancers, and melanoma. Men with these mutations have a higher risk of breast, pancreatic, prostate, and testicular cancers.

Women with BRCA gene mutations are five times more likely to develop breast cancer than women without a mutation. Hereditary BRCA mutations account for about 5 to 10 percent of all breast cancers and 10 to 15 percent of all ovarian cancers among white women in the United States.

People whose family history suggests that they may have a harmful BRCA gene mutation can undergo genetic testing.

People with a harmful BRCA mutation have several options that may help reduce their risk of developing cancer: screening and other forms of surveillance; surgery to remove at-risk tissue; behavioral changes, such as losing weight and increasing physical activity; and taking drugs that have been shown to reduce the risk of breast cancer.

Notes

Director's Consumer Liaison Group to Meet Next Week

The NCI Director’s Consumer Liaison Group (DCLG) will meet October 25 and 26 in Bethesda, MD. The meeting will feature presentations and discussions about how research advocates can help research findings make their way into routine clinical practice more quickly. Attendees will also hear an update on NCI activities.

The DCLG provides informed, nonscientific perspectives to the NCI director on promoting research outcomes that are in the best interests of cancer patients. Specifically, DCLG members provide insight into enhancing input, optimizing outreach, and promoting strong collaborations, all with respect to nonscientist stakeholders, in the interest of meeting common institute and community goals.

The meeting is open to the public and the agenda is available online. Please register by e-mailing Frances Young at frances.young@nih.gov or calling 301-435-7788.

Meet NCI Experts at the American Public Health Association Annual Meeting

NCI at APHA 2012 tile

NCI will participate in the American Public Health Association (APHA) 140th Annual Meeting, which will be held October 27–31 at the Moscone Center in San Francisco.

APHA attendees can learn more about NCI’s funding opportunities, cancer information resources, research, cancer control programs, and fellowships at NCI Exhibit Booth #2425. Attendees can also connect with NCI staff at the exhibit booth during the Meet the Experts Sessions and attend sessions involving NCI staff.

For a list of session with NCI staff and activities at NCI’s exhibit booth, visit NCI's APHA 2012 webpage.

NCI Reaches Facebook Milestone

Screenshot of NCI's Facebook page NCI’s Facebook page topped 15,000 “likes” this week. Launched in 2010, the platform provides a way for users to interact with NCI, keep up to date with institute activities, and to share their own perspectives. The page includes questions and discussions initiated by group members, as well as links to NCI resources and cancer news.

“We consider this a significant milestone,” said Deb Pearson, community manager for NCI’s Facebook page who also helps oversee NCI’s Cancer Information Service. “It’s a great platform for people to request and share information, and it also informs us about the needs and stories of those in the cancer community. For a growing number of people, social media channels are how they choose to reach out. We are happy that we can accommodate them.”