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Updated look reflects a more public-facing direction for the AACR to raise awareness and support for cancer research
PHILADELPHIA — The American Association for Cancer Research (AACR), the world’s largest scientific organization dedicated to accelerating advances against cancer, unveiled a new logo and brand identity today that is designed to engage more members, patient advocates, cancer survivors, and the general public in the AACR’s mission to speed the prevention and cure of all cancers.
The new identity begins its official launch today on the AACR’s new website, www.AACR.org, with a robust public awareness campaign to follow in the fall of 2014 through the AACR Foundation.
"Amazing progress has been made against cancer because of the dedicated work of researchers throughout the biomedical research enterprise, but future advances in understanding and treating cancer will depend on public support," said Margaret Foti, PhD, MD (h.c.), chief executive officer of the AACR. "As national budget pressures increase, federal government funding of cancer research is decreasing. Our new awareness campaign positions the AACR as a major fundraising and grant-giving organization for highly meritorious, innovative cancer science and medicine. The AACR is changing the way it presents itself to both the scientific community and the public, and is providing a visual ‘shorthand’ message that more clearly and boldly tells the story and the amazing impact of our organization. This is not just a new logo. It is the mark of a new—more public-facing—direction for the AACR."
The new logo is designed to be distinctive and bold, according to Foti. "There is a visual narrative, a connection between the ‘R’ and the ‘C’ that reflects the inextricable link between research and the goal of eradicating cancer. The green color of the logo implies hope, life, and growth. The tagline ‘Finding Cures Together’ conveys the essential collaboration between the AACR, its research partners around the world, the AACR Foundation, and the funding public as they all work together urgently to address this complex disease," said Foti.
As part of these organizational efforts, the AACR is growing its membership base, identifying the next frontiers in cancer research, increasing its advocacy efforts, and investing more resources to deliver accurate and timely cancer information to the public. The AACR continues to expand globally, opening an office in China, its first satellite office outside the United States. More than 30 percent of the AACR’s 34,000 members currently reside outside the United States.
"This is a very exciting period of growth and new direction for the AACR," said Foti. "The way we present ourselves to all of our constituencies now reflects this dynamism."
To view the new logo and brand identity of the AACR, visit the organization’s website at www.AACR.org.
New Approach Identifies Cancer Mutations as Targets of Effective Melanoma Immunotherapy
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PHILADELPHIA —A new approach demonstrated that the recognition of unique cancer mutations appeared to be responsible for complete cancer regressions in two metastatic melanoma patients treated with a type of immunotherapy called adoptive T-cell therapy. This new approach may help develop more effective cancer immunotherapies, according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research.
Steven A. Rosenberg, MD, PhD
“This study provides the technical solution to identify mutated tumor targets that can stimulate immune responses, which is one of the major bottlenecks in developing a new generation of adoptive T-cell therapy,” said Steven A. Rosenberg, MD, PhD, chief of surgery at the National Cancer Institute (NCI) in Bethesda, Maryland. “The two targets identified in this study play important roles in cancer cell proliferation.
“Immunotherapy has the potential to successfully treat cancer by targeting tumor mutations. We’ve moved one step closer because of this study,” Rosenberg added.
Adoptive T-cell therapy is a type of immunotherapy in which the immune cells infiltrating a patient’s tumor, so called tumor-infiltrating lymphocytes (TILs, which are T cells), are harvested, activated and expanded in the laboratory, and transferred back to the patient. Such activated cells are capable of efficiently attacking tumor cells.
“In a clinical trial, up to 72 percent of the patients with metastatic melanoma experienced tumor regression after adoptive T-cell transfer. However, not all patients benefited. This is because the specificity of the TILs remains largely unclear. Our goal was to establish an efficient method to identify the specificity of these cells,” explained Rosenberg.
The researchers took tumor samples from two patients who had benefited from the therapy and pursued two screening approaches to identify the tumor targets recognized by the clinically effective T cells. First, they used a conventional screening method called cDNA library screening to identify nonmutated targets. Second, they used a novel method called tandem minigene library screening to identify mutated targets that cannot be found by the conventional method of screening.
For the second approach, the researchers used next-generation DNA sequencing to sequence the coding regions of the DNA from the two patients’ tumors, and identified mutations. Next, they generated a library of these mutations. Instead of synthesizing the entire mutated gene, they synthesized only a small region surrounding the mutation (hence the name “minigene” library). They then screened the minigene library to identify those targets in the patients’ tumors that were recognized by their TILs.
Using cDNA library screening, the researchers identified three novel nonmutated tumor targets, and four previously known non-mutated tumor targets.
Using tandem minigene library screening, they identified two novel mutated tumor targets, KIF2C and POLA2, which play important roles in cell proliferation.
With the minigene library approach, Rosenberg and colleagues recently reported another novel tumor target recognized by the activated T cells of a patient with bile duct cancer, who responded to adoptive T-cell transfer.
This study was funded by the NCI Director’s Innovation Award, the NCI Intramural Research Program, the Adelson Medical Research Foundation, the Milstein Family Foundation, and the European Research Council. Rosenberg declares no conflicts of interest.
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PHILADELPHIA — The longer a person took low-dose aspirin, the lower his or her risk for developing pancreatic cancer, according to a study published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.
Harvey A. Risch, MD, PhD
“We found that the use of low-dose aspirin was associated with cutting the risk of pancreatic cancer in half, with some evidence that the longer low-dose aspirin was used, the lower the risk,” said Harvey A. Risch, MD, PhD, professor of epidemiology in the Department of Chronic Disease Epidemiology at the Yale School of Public Health in New Haven, Connecticut. “Because about one in 60 adults will get pancreatic cancer and the five-year survival rate is less than 5 percent, it is crucial to find ways to prevent this disease.”
Men and women who took low-dose aspirin regularly had 48 percent reduction in their risk for developing pancreatic cancer. Protection against pancreatic cancer ranged from 39 percent reduction in risk for those who took low-dose aspirin for six years or less, to 60 percent reduction in risk for those who took low-dose aspirin for more than 10 years.
“Older studies of aspirin use have been clouded by the use of [regular- or high-dose] aspirin for pain relief from conditions that themselves might be related to the risk for pancreatic cancer. Only recently have people been using low-dose aspirin for long enough times [to prevent cardiovascular disease] that the use might bear on risk of pancreatic cancer development,” explained Risch.
“There seems to be enough evidence that people who are considering aspirin use to reduce the risk for cardiovascular disease can feel positive that their use might also lower their risk for pancreatic cancer, and quite certainly wouldn’t raise it,” Risch added.
Study subjects were recruited from the 30 general hospitals in Connecticut between 2005 and 2009. There were 362 pancreatic cancer cases and 690 controls. Study subjects were interviewed in person to determine when they started using aspirin, the number of years they used aspirin, the type of aspirin they used (low versus regular dose), and when they stopped using aspirin, among other things. Confounding factors, including body mass index, smoking history, and history of diabetes, were taken into account.
Of the study participants, 57 percent were men, about 92 percent were non-Hispanic white, about 49 percent were former or current smokers, and 19 percent had been diagnosed with diabetes within the three years prior to this study.
A dose of 75 to 325 mg of aspirin per day was considered as low-dose aspirin (usually taken for heart-disease prevention), and a dose higher than that, generally taken every four to six hours, was considered as regular-dose aspirin taken for pain or anti-inflammation purposes.
Of the participants, 96 percent of low-dose aspirin users and 92 percent of regular-dose aspirin users reported daily aspirin use.
The earlier a person started regularly taking low-dose aspirin, the greater the pancreatic cancer risk reduction, ranging from 48 percent reduction in those who started three years before the study, to 60 percent in those who started taking it 20 years before the study. On the other hand, discontinuation of aspirin use within two years prior to the study was associated with a threefold increased risk for pancreatic cancer compared with continuing use.
“People who are developing pancreatic cancer have various physiologic changes, including taste disorders, starting to occur two to three years before pancreatic cancer is diagnosed. Such individuals are more likely to quit using aspirin. So it may be tricky to separate the various aspects of patterns of aspirin use and risk of pancreatic cancer,” noted Risch.
“Aspirin use has potential risks of its own, and thus the risks and benefits for each person have to be evaluated based on personal characteristics and considerations,” added Risch. “For the small subset of individuals with strong family histories of pancreatic cancer or who otherwise have been evaluated to be at substantially increased risk of pancreatic cancer, aspirin use could be part of a regimen designed to reduce their risk.”
This study was funded by the National Cancer Institute. Risch declares no conflicts of interest.
Combination Tumor Imaging Can Distinguish Malignant and Benign Breast Tumors, Help Avoid Unnecessary Biopsies
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PHILADELPHIA — Imaging breast tumors using four approaches together can better distinguish malignant breast tumors from those that are benign, compared with imaging using fewer approaches, and this may help avoid repeat breast biopsies, according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research.
Katja Pinker, MD
“By assessing many functional processes involved in cancer development, a multiparameter PET-MRI of the breast allows for a better differentiation of benign and malignant breast tumors than currently used DCE-MRI alone. Therefore, unnecessary breast biopsies can be avoided,” said Katja Pinker, MD, associate professor of radiology in the Department of Biomedical Imaging and Image-guided Therapy at the Medical University of Vienna in Austria.
The new imaging technique, called multiparametric (MP) 18FDG PET-MRI, which used four imaging approaches, was 96 percent accurate in distinguishing malignant breast tumors from those that were benign, and provided better results than combinations of two or three imaging approaches. The study estimates that this technique can reduce unnecessary breast biopsies recommended by the commonly used imaging method, the DCE-MRI, by 50 percent.
“DCE-MRI is a very sensitive test for the detection of breast tumors, but is limited in visualizing the functional properties cancer cells acquire during development. Therefore, there is still room for improvement,” explained Pinker. “PET-MRI mirrors cancer biology and allows accurate diagnosis of breast cancer without a biopsy. Additionally, the more accurately we understand a tumor’s biology, the better we can tailor therapy to each breast cancer patient’s individual needs.
“Provided that a hospital is equipped with a PET-CT and an MRI scanner or a combined PET-MRI, the technique we have described can be immediately implemented in clinics,” said Pinker.
Pinker and colleagues recruited 76 patients to the study who had suspicious or inconclusive findings from a mammography or a breast ultrasonography. They performed a MP 18FDG PET-MRI on all the patients. In addition, all patients’ breast tumor biopsies were evaluated by histopathology.
To determine the combination of imaging parameters that yielded the most accurate results, Pinker and colleagues combined the imaging data from two parameters, three parameters, and all four parameters. All two-parameter and three-parameter evaluations included DCE-MRI.
All results were compared with histopathology diagnosis to evaluate which combination was most efficient in making an accurate diagnosis. Of the 76 tumors, 53 were malignant and 23 were benign, based on histopathology.
The researchers found that none of the two- or three-parameter combinations reached the same level of sensitivity and specificity as the four-parameter method, which had an AUC of 0.935. (An AUC of 0.9 to 1 means the method is excellent, and an AUC of 0.5 means the method is worthless.)
“Performing a combined PET-MRI is currently less cost-effective than existing breast imaging methods,” said Pinker. “However, a significant reduction in unnecessary breast biopsies by using this combined method may improve the cost-effectiveness.”
MP 18FDG PET-MRI allowed tumor imaging by four parameters: DCE-MRI, DWI, 3D 1H-MRSI, and 18FDG-PET.
Thomas Helbich, MD, MBA, is the senior author of this study and head of this study group.
This study was funded by the Austrian Society of Senology Scientific Funding Award, the Austrian National Bank “Jubiliaemsfond” Project, and the Medical Scientific Fund of the Mayor of Vienna Project. Pinker declares no conflicts of interest.
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PHILADELPHIA — Pancreatic ductal adenocarcinomas (PDAC) do not typically respond to immunotherapy, which limits treatment options for this cancer. By priming with a therapeutic vaccine and a low-dose chemotherapy combination prior to surgery, researchers converted PDACs into immunogenic cancers that may respond to immunotherapy, according to a study published in Cancer Immunology Research, a journal of the American Association for Cancer Research (produced in collaboration with the Cancer Research Institute).
Lei Zheng, MD, PhD
“The only curative treatment for pancreatic cancer is complete surgical resection, and approximately 80 percent of patients who undergo surgery relapse and die from the disease within five years, suggesting a need for effective strategies,” said Lei Zheng, MD, PhD, assistant professor of oncology and surgery at the Sidney Kimmel Comprehensive Cancer Center and the Skip Viragh Center for Pancreatic Cancer Research and Clinical Care at the Johns Hopkins University School of Medicine in Baltimore.
In this clinical trial, pretreatment of PDAC patients with the vaccine GVAX and low doses of the chemotherapy cyclophosphamide caused the aggregation of immune cells inside the patients’ tumors, and many of these immune cells expressed proteins that may make these cancers amenable to immunotherapies such as PD-1 inhibitors.
“Pancreatic cancer is one of a number of malignancies that typically lack tumor-infiltrating effector lymphocytes and have been considered ‘nonimmunogenic’ neoplasms,” added Zheng. “This situation has drastically slowed the development and application of immune-based therapies for these cancers.
“Our study shows for the first time that treatment with a vaccine-based therapy directly reprograms the pancreatic cancer microenvironment, allowing the formation of lymphoid aggregates, which are organized, lymph node-like, functional immune structures, and which convert an immunologically quiescent tumor into an immunologically active tumor,” Zheng said.
Between 2008 and 2012, Zheng and colleagues enrolled 59 patients with PDAC to this study and randomized them among three arms: Patients in arm A received GVAX alone, patients in arm B received GVAX plus a single intravenous dose of cyclophosphamide at 200 mg/m2, and patients in arm C received GVAX plus 100 mg oral doses of cyclophosphamide once daily, on alternate weeks.
About two weeks after vaccination, all patients underwent surgery to remove their pancreatic tumors. Of the 59 patients, 39 remained grossly free of disease after surgery and underwent further treatment with chemotherapy and radiotherapy, and their tumors were analyzed in this study.
In addition to tumor samples from the 39 patients, the researchers used, for the comparative analyses, tumor samples from 58 patients from other studies: Four were unvaccinated patients and 54 were patients whose tumor samples were collected prior to vaccination.
They found that the vaccine-chemotherapy combination resulted in the formation of lymphoid aggregates within the tumors in 33 of the 39 patients within two weeks of vaccination.
Extensive analysis of the various immune cell types found in the tumors after vaccination revealed an increase in the ratio of effector T cells to regulatory T cells. According to Zheng, this meant that the tumors had become immunogenic and the immune cells in the tumor area were capable of fighting the cancer cells. An increase in the ratio was associated with better survival.
The researchers also found that the tumors from patients who survived for more than three years after vaccine therapy had enhanced signaling pathways that promote immune responses, compared with those who survived for less than 1.5 years following vaccination.
“We are further dissecting the immune signatures within the lymphoid aggregates to study the TGF-beta and Th17 signaling pathways. TGF-beta and Th17 pathways may also be key targets, in addition to PD-1/PD-L1, for treatments that enhance vaccine-induced antitumor immune responses in pancreatic cancer,” said Zheng.
“Our study has suggested a new model for developing more effective immunotherapy for traditionally nonimmunogenic tumors like pancreatic cancer,” Zheng added. “We will next investigate immunotherapies that include both cancer vaccines and treatments that boost the ‘good’ immune-regulatory signals or block the ‘bad’ immune-regulatory signals.”
This study was funded by the National Institutes of Health, the Johns Hopkins School of Medicine Clinical Scientist Award, the American Society of Clinical Oncology Young Investigator Award, the Viragh Foundation and the Skip Viragh Pancreatic Cancer Center at Johns Hopkins, the National Pancreas Foundation, the Lefkofsky Family Foundation, the Lustgarten Foundation, the Sol Goldman Pancreatic Cancer Center, and the AACR-FNAB Fellows Grant for Translational Pancreatic Cancer Research Award. Zheng declares no conflicts of interest.
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PHILADELPHIA — Survivors of childhood cancers were hospitalized more often and for longer durations because of blood disorders and other problems, many years after cancer treatment was completed, compared with the general population, according to a study published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.
Anne C. Kirchhoff, PhD, MPH
“Our findings demonstrate that childhood cancer survivors face ongoing problems that can lead to hospitalization, even for those who are decades past their original cancer diagnosis. This can negatively impact their quality of life,” said Anne C. Kirchhoff, PhD, MPH, assistant professor of pediatrics at the Huntsman Cancer Institute of the University of Utah in Salt Lake City.
“Regular cancer-focused health care is important for identifying health problems for survivors throughout their lives,” Kirchhoff added. “Patients and families who have experienced childhood cancer should obtain a cancer treatment summary and recommendations for follow-up care from their oncologist, and coordinate their follow-up care with their oncology and primary care doctors to ensure their health care needs are being managed.”
In this study, survivors were 52 percent more likely to be hospitalized, and their number of admissions was 67 percent higher, compared with age and sex-matched individuals who did not have cancer. Survivors were also 35 percent more likely to have stayed longer every time they were hospitalized, compared with controls.
“The Affordable Care Act has several provisions that will improve insurance for cancer survivors, including expanding coverage to dependents up to age 26, prohibiting insurance denials based on health status, and eliminating lifetime limits on coverage,” noted Kirchhoff. “Better insurance coverage should hopefully help survivors identify and manage health problems at earlier, less costly stages.”
Kirchhoff and colleagues identified 1,499 childhood cancer survivors treated between 1975 and 2005 who were at least five years past their original cancer diagnosis from the Utah Population Database (UPDB) and the Utah Cancer Registry. They collected information including demographics, type of cancer, and type of treatment. Data on subsequent hospitalizations were obtained from the Utah Department of Health hospital discharge records. Using UPDB, they also identified 7,713 subjects who did not have cancer, who served as age and sex-matched controls in this study.
About 50 percent of the survivors included in this study were female, and 98 percent were non-Hispanic white. The researchers found that both female survivors and male survivors were more likely to have been hospitalized than their respective controls. Female survivors also had a longer average length of hospital stay than female controls.
More than 10 percent of survivors of central nervous system tumors, neuroblastoma, or malignant bone tumors were hospitalized five or more times during the follow-up period, and the hospital admission rates were approximately two times higher for survivors of neuroblastoma and bone tumors, respectively, compared with controls. “We saw higher rates of hospitalization across most cancer types, but not for all cancers, which gives us clues as to which groups of survivors may need better surveillance in the long term,” said Kirchhoff.
Common reasons for hospitalizations for survivors compared with the controls included conditions like blood disorders (such as anemia) and cancer, although it is unclear if this was for their original cancer diagnosis or new cancers. Infections, nervous system problems, and respiratory problems were other leading reasons for hospitalization.
Kirchhoff and colleagues will conduct further analyses to better understand the reasons survivors are hospitalized and their hospital-related costs.
This study was funded by a Huntsman Cancer Institute Cancer Control and Population Sciences Research Award, the Huntsman Cancer Foundation, a Primary Children’s Medical Foundation Career Development Award, the Utah Cancer Registry, and the National Institutes of Health. Kirchhoff declares no conflicts of interest.
American Association for Cancer Research to Participate in Upcoming Twitter Chat on the Promise of Immunotherapy
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The American Association for Cancer Research (AACR) will partner with Time magazine, Mayo Clinic Cancer Center, and Cancer Research Institute for a Twitter chat titled “The Promise of Immunotherapy,” Wednesday, June 18, 1-2 p.m. ET.
Immunotherapy is a unique approach to cancer treatment that restores the immune system’s ability to detect and eliminate cancer cells.
Esteban Celis, MD, PhD, a member of the AACR Cancer Immunology Steering Committee and professor of medicine at Georgia Regents University Cancer Center, will represent the AACR on this Twitter chat, which will be moderated by Time magazine’s Senior Health Reporter Alice Park.
Follow the conversation on Twitter and join us: #CIMchat
Follow the AACR on Twitter: @AACR
For more information, please contact Jeremy Moore at jeremy.moore@aacr.org or 215-446-7109, or Lauren Riley at lauren.riley@aacr.org or 215-446-7155.
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PHILADELPHIA — Among new adolescent smokers, boys were more likely to discontinue smoking than girls, and both boys and girls who found package warning labels to be intimidating were also more likely to stop, according to a study published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.
“Currently, few longitudinal studies identify factors that help or hinder young smokers to stop smoking,” said Jennifer O’Loughlin, Ph.D., professor in the Department of Social and Preventive Medicine at the University of Montreal in Quebec, Canada. “In our study, we learned that male sex, older age, cigarette package warnings, and participation in team sports helped with smoking discontinuation, while family stress, worry about weight, being overweight, illicit drug use, and cravings for cigarettes hindered.”
Of the students who participated in the Nicotine Dependence in Teens (NDIT) study and who smoked at least occasionally, boys were 80 percent more likely to discontinue smoking than girls, and older adolescents were 30 percent more likely to discontinue than younger adolescents. Participants who said cigarette package warnings made them afraid to smoke and those who participated in team sports were 44 percent and 40 percent more likely to quit, respectively.
“Overall, these results support that healthy family habits, which include nonsmoking as the norm as well as positive exchange and functioning, will help novice smokers discontinue smoking,” said O’Loughlin. “Parents who smoke should understand the effects of their smoking on their children, and families should work together or with professionals to identify and reduce sources of family stress. Parents should engage their children in sports and other healthy activities.
“It is imperative that we better understand the factors that promote smoking discontinuation in girls compared with boys, so that we can design gender-specific interventions,” she added.
O’Loughlin and colleagues next plan to develop a nomogram, a short screening tool, to help health practitioners distinguish between youths who likely need intervention to help them stop smoking from those who do not.
From 1999 to 2000, students ages 12 or 13 from 10 secondary schools in Montreal were enrolled in the NDIT study. Of the 1,293 participants, 706—262 boys and 444 girls—who reported smoking at enrollment or who initiated smoking during follow-up were included in this study. After collecting baseline data including self-report questionnaires and anthropometric measurements, the researchers collected follow-up data every three months for the next five years, until the participants completed secondary school. The analysis included data for 620 participants.
Forty-three percent of the participants’ parents smoked, 87 percent had friends who smoked, and 78 percent reported often seeing their teachers or other school staff smoking.
The researchers found that 40 percent of the study participants discontinued smoking during follow-up. Discontinuation was defined as a student reporting no cigarette smoking in at least four consecutive follow-up cycles over a one-year period.
Students who reported family stress, who worried about weight, who were overweight, who used illicit drugs, who had higher tolerance to cigarette smoke, or who had other nicotine dependence symptoms were 10 to 30 percent less likely to discontinue smoking.
“The predictors we identified make good sense and several are amenable to intervention, which is good news,” said O’Loughlin.
This study was funded by the Canadian Cancer Society. O’Loughlin declares no conflicts of interest.
Exposure to Organic Solvents Before First Childbirth May Increase Hormone-related Breast Cancer Risk
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PHILADELPHIA — Among women with a family history of breast cancer, those who worked with organic solvents prior to their first full-term birth had an increased risk for hormone receptor-positive breast cancer, according to data published in Cancer Research, a journal of the American Association for Cancer Research.
Christine C. Ekenga, Ph.D.
“The time between puberty and before first birth is an important period of development when the breast may be more vulnerable to chemical exposures,” said Christine C. Ekenga, Ph.D., a postdoctoral fellow in the epidemiology branch of the National Institute of Environmental Health Sciences (NIEHS) at the National Institutes of Health (NIH). “We observed that women who started working with solvents before their first full-term birth had a greater risk for breast cancer.
“We identified several occupations where solvent exposure was associated with an elevated risk for breast cancer,” added Ekenga. “These include clinical laboratory technicians, maids and house cleaners, and production [factory] workers. All women should be familiar with the chemicals and hazards that are present in their workplace, and use personal protective equipment and minimize exposures when appropriate.”
Women who worked with organic solvents prior to their first full-term birth had about a 40 percent increased risk for developing hormone receptor-positive, invasive breast cancer, and all women who worked in clinical laboratories had a twofold increased risk for this type of breast cancer.
“Our study is an important first step toward understanding how the timing of chemical exposures may impact breast cancer risk,” said Ekenga. “We hope that our findings will generate additional interest in the possible role of solvents and other chemicals in the etiology of breast cancer.”
To study the relationship between occupational exposure to solvents and breast cancer, Ekenga and colleagues used data from the Sister Study led by Dale P. Sandler, Ph.D., at the NIEHS, a prospective cohort study of 50,884 initially breast cancer-free sisters of women who had been diagnosed with breast cancer.
Participants were enrolled between 2003 and 2009, and they answered questionnaires about their occupational history and other potential breast cancer risk factors. Questions included duration of solvent exposure at the job, weekly frequency of exposure, and age at first job involving organic solvents. Participants were followed up annually for health updates. Evaluable data were available for 47,661 women.
Of the study participants, 1,798 were diagnosed with breast cancer during follow-up, of whom 1,255 had invasive cancer. Of the invasive tumors, 77 percent were hormone-receptor positive.
After adjusting for confounders including race/ethnicity, parity, exposure to tobacco smoke, and working night shifts, overall, there was no increased risk for invasive breast cancer from lifetime exposure to solvents, but the researchers found exposure to solvents prior to first full-term birth to be a critical period for breast cancer risk. A nonsignificant elevated risk was observed for women who worked as maids and housekeeping cleaners, and those who had factory-related occupations.
“Additional research is needed to characterize the types of solvents used by women in different occupational settings and the levels at which women are exposed to solvents in the workplace,” said Ekenga.
This study was funded by the Intramural Research Program of the NIH. Ekenga declares no conflicts of interest.
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PHILADELPHIA — Women whose early-stage breast cancers had reduced numbers of copies of the LRIG1 gene were more likely to have a relapse or die of their disease, according to data published in Cancer Research, a journal of the American Association for Cancer Research.
“Tumors with metastatic capability have cells within them that have stem cell-like properties, which resist chemotherapy, tend to sit quietly in the tumor, and are most likely the source of metastatic spread,” said Patricia A. Thompson, Ph.D., an associate professor in the Department of Cellular and Molecular Medicine and leader of the Cancer Prevention and Control Program at the University of Arizona Cancer Center in Tucson. “LRIG1 is a protein that is thought to control the growth of these cells and keep them quiet.”
Human cells have two copies of most genes. An increase or decrease in copy-number of certain genes is implicated in several diseases, including cancer.
Among women who were diagnosed with stage 1 or stage 2 breast cancers, those whose tumors had loss of LRIG1 copy-numbers were almost twofold more likely to have a relapse, 2.39-fold more likely to have a relapse five years after diagnosis or later, and 1.55-fold more likely to die of their disease, compared with those whose tumors did not have loss of LRIG1 copy-numbers. Stage 1 and stage 2 breast cancers are generally considered to be at a lower risk for a relapse. These results could help clinicians identify those at increased risk and monitor them more carefully.
“First, we found that the loss of LRIG1 gene copy-numbers in tumors of early-stage patients was associated with a higher risk of disease relapse, metastasis, and death,” said Thompson. “Second, we observed that the patients whose tumors had an increase in the copy-numbers of LRIG1 had much better clinical and pathology characteristics, generally. This suggested that the gain of LRIG1 copy-numbers may contribute to the lower risk observed in these patients.”
Thompson and colleagues used breast cancer tissue samples from 971 women who were treated at MD Anderson Cancer Center for stage 1 or stage 2 breast cancers between 1985 and 2000. This analysis was a joint collaboration between investigators at MD Anderson Cancer Center and the Baylor College of Medicine in Houston, and the University of Umeå in Sweden.
They used a high-resolution molecular inversion probe array with 300,000 probes, 12 of which detected alterations in LRIG1. This technology is best suited for samples that have been stored for long periods of time and was vital for this project, said Thompson.
Of the 971 samples, 3.7 percent had gain, and 8.9 percent had losses in LRIG1 copy-numbers. The researchers also found that LRIG1 copy-number loss was more common in triple-negative (13.8 percent) and HER2-positive (12.3 percent) breast cancers, which have worse prognosis, compared with luminal A and luminal B subtypes (less than 10 percent).
LRIG1 copy-number loss was also more prevalent in samples from black and Hispanic women (12.8 and 12.2 percent, respectively), who often have worse breast cancer outcomes, compared with samples from non-Hispanic white women (7.7 percent).
The researchers found that LRIG1 copy-number loss was significantly associated with disease relapse, distant metastasis, and death.
The researchers next used data from pooled, publicly available data sets yielding 1,576 samples to analyze alterations in LRIG1 and found that low expression of this gene was associated with increased distant metastasis and death, compared with medium or high expression. “Given that these results are such a strong replication of our findings from really old samples, we were very excited,” said Thompson.
Outcomes from these two analyses did not change even after adjusting for known factors that influence relapse and metastasis, leading the researchers to conclude that alteration in LRIG1 copy-numbers is an independent risk factor for breast cancer metastasis and death in otherwise low-risk patients.
“Measurement of the expression levels of LRIG1 as RNA or protein would be more clinically relevant and we would like to see the development of such an assay,” said Thompson. “Efforts in developing LRIG1 as a tumor marker would help in developing new agents to kill or silence these cells as a means to prevent breast cancer relapse and metastasis.
“Our ability to identify patients as being at high risk for relapse versus at those at very low risk is dramatically improving,” Thompson added.
This study was funded by the National Institutes of Health and Susan G. Komen. Thompson declares no conflicts of interest.
Five or More Blistering Sunburns Before Age 20 May Increase Melanoma Risk by 80 Percent
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PHILADELPHIA — The risk of developing the most deadly form of skin cancer, melanoma, was more closely related to sun exposure in early life than in adulthood in young Caucasian women, according to a study published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.
Abrar A. Qureshi, M.D., MPH
“Our results suggest that sun exposures in both early life and adulthood were predictive of nonmelanoma skin cancers, whereas melanoma risk was predominantly associated with sun exposure in early life in a cohort of young women,” said Abrar A. Qureshi, M.D., MPH, professor and chair of the Department of Dermatology at Warren Alpert Medical School of the Brown University and Rhode Island Hospital in Providence.
After following 108,916 Caucasian registered nurses for about 20 years, this study found that those who had at least five blistering sunburns when they were 15 to 20 years old had a 68 percent increased risk for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin, and an 80 percent increased risk for melanoma. Those who were exposed to the highest amounts of cumulative ultraviolet (UV) radiation in adulthood had no increased risk for melanoma, but had a 2.35-fold and 2.53-fold increased risk for developing BCC and SCC of the skin.
“Pattern of sun exposure was not uniformly associated with the risk for all the three main skin cancers we see in the United States, suggesting that there are some differences in the pathophysiology of these skin cancers,” said Qureshi. “An individual’s risk of developing skin cancer depends on both host and environmental risk factors. Persons with high host-risk traits, such as red hair color, higher number of moles, and high sunburn susceptibility, should pay more attention to avoid excessive sun exposure, especially early in life.”
Participants were from the Nurses’ Health Study II. At the time of registration they were between the ages of 25 and 42 and resided in 14 different states. At registration, the participants responded to a baseline questionnaire about their medical histories and potential risk factors for skin cancers, including number of moles on legs, number of blistering sunburns between age 15 and 20, and family history of melanoma.
Updated health information was collected every two years for about 20 years. During this time, participants answered additional questions related to skin cancer risk, including updated family history, tanning bed use, smoking and alcohol consumption habits, and body mass index.
The researchers took into account the duration participants spent residing at different locations in the United States during follow-up to calculate the cumulative UV exposure for each individual, and then grouped the participants under three categories of UV exposure: low, medium, and high baseline annual UV flux.
About 24 percent of the participants had experienced painful blisters as a child or adolescent, about 10 percent had more than five blistering sunburns between ages 15 and 20, and about 24 percent had used tanning beds.
Of the study participants, 6,955 were diagnosed with BCC, 880 were diagnosed with SCC of the skin, and 779 were diagnosed with melanoma. Of those with melanoma, 445 had invasive cancer.
After adjusting for potential confounders, Qureshi and colleagues found a strong dose-response relationship between cumulative UV flux and risk for BCC and SCC of the skin, but no such association was seen for melanoma. Those who had at least five blistering sunburns between ages 15 and 20 had increased likelihood for developing any of the three types of skin cancers, but the greatest risk was for developing melanoma.
The researchers also found that the host-risk profile may alter an individual’s risk for developing sun exposure-associated, nonmelanoma skin cancers.
“Parents may need to be advised to pay more attention to protection from early-life sun exposure for their kids in order to reduce the likelihood of developing melanoma as they grow up,” said Qureshi. “Older individuals should also be cautious with their sun exposure, because cumulative sun exposure increases skin cancer risk as well.”
This study was funded by the National Institutes of Health, and the Brigham and Women’s Hospital. Qureshi serves as a consultant for Abbott, Centocor, Novartis, and the Centers for Disease Control and Prevention.
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