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New Cancer Research Blog Makes Its Debut1435367/16/2014 1:17:08 PM Releases/AllItems.aspx568False2014-07-16T12:00:00Z<div class="ExternalClass0D81F5961F09401E9A61247589F45144"><p>PHILADELPHIA — The American Association for Cancer Research is pleased to announce the launch of its new blog, <a href="http&#58;//" target="_blank"><em>Cancer Research Catalyst</em>. </a></p><p>As our chief executive officer, Margaret Foti, PhD, MD (h.c.), notes in her <a href="http&#58;//" target="_blank">welcome post</a>, the goal of <em>Cancer Research Catalyst </em>is to increase the spread of knowledge about cancer research while providing helpful and timely information for our members and the public. Posts will cover a range of topics, including research from our journals and meetings, policy and advocacy issues, and AACR initiatives. </p><p>We want <em>Cancer Research Catalyst</em> to be an interesting and useful resource, and we welcome your feedback. We invite you to take a look and send any comments or suggestions to <a href="mailto&#58;"></a>. Follow us by adding the blog to your RSS feed or signing up to receive each post via email.</p><p>As you may have noticed, this blog is just one part of a major online refresh for the AACR, which includes our new brand identity, <a href="http&#58;//" target="_blank">logo</a>, and <a href="/" target="_blank">website</a>. ​</p></div>
Gene Signature May Predict Breast Cancer Treatment Response to Tamoxifen1406687/15/2014 1:23:18 PM Releases/AllItems.aspx567False2014-07-15T04:05:00Z<div class="ExternalClass90EF6FDACCBB4E75AE02D3968A72F8FA"><p>PHILADELPHIA — A gene signature identified using a new approach has the potential to be used in the clinic to predict which patients with estrogen receptor-positive breast cancer will benefit from tamoxifen therapy after surgery, according to data published in <em><a href="http&#58;//" target="_blank">Cancer Research</a></em>, a journal of the American Association for Cancer Research.&#160;<img alt="René Bernards, PhD" src="/PublishingImages/Bernards_Rene_150x200.jpg" style="margin&#58;10px;float&#58;right;vertical-align&#58;auto;" /></p><p>“We have used a very innovative approach to identify genes that help foretell whether a patient will respond to tamoxifen, and we showed that this gene signature performed well in two large patient groups,” said <a href="http&#58;//" target="_blank">René Bernards, PhD</a>, professor and head of the Division of Molecular Carcinogenesis at the <a href="http&#58;//" target="_blank">Netherlands Cancer Institute</a> in Amsterdam.</p><p>“About one-third of women with hormone receptor-positive breast cancer experience a relapse after adjuvant treatment with tamoxifen. Median overall survival in these patients, even with further treatment, is around 30 to 45 months,” explained Bernards. “It has been very difficult to identify patients whose tumors lack a proper response to tamoxifen, the most frequently used drug in breast cancer.</p><p>“By using CHIPseq and RNAseq technologies in combination with RNA expression data from publically available data sets, we were able to translate results from cell culture experiments into a diagnostic tool that has the potential to help identify breast cancer patients that will benefit from tamoxifen,” added Bernards.</p><p>To find out whether loss of function of certain genes is involved in resistance to tamoxifen, Bernards and colleagues took human hormone receptor-positive breast cancer cells and infected them with thousands of small pieces of RNA called shRNAs, each designed to silence a specific gene. By studying the shRNAs that survived despite treatment with tamoxifen, they identified a gene called USP9X, whose loss of function in breast cancer cells resulted in tamoxifen resistance.</p><p>Next, the researchers identified other genes that were altered during treatment with tamoxifen, in the absence of USP9X. Then, using publicly available data sets, they studied the expression of these specific genes in patients who were treated with tamoxifen after surgery, and whose treatment outcomes were known. They found that the data split into two groups, one with a gene signature with a good outcome, and the other with a signature showing bad outcome, after treatment with tamoxifen.</p><p>The gene signature they identified could not predict treatment outcomes in patients who did not receive tamoxifen therapy, suggesting that this signature is specific to outcomes with tamoxifen treatment.</p><p>Collectively, the researchers used data from about 680 patients from four different data sets to test the utility of the gene signature in predicting responses to tamoxifen therapy in hormone receptor-positive breast cancer patients.</p><p>“We are currently validating our promising results using the data from a prospective randomized controlled trial, and we expect to complete this validation by the end of this year,” said Bernards. “If this is successful, clinical implementation is a logical next step.”</p><p>This study was funded by grants from the Dutch Cancer Society. Bernards declares no conflicts of interest.​</p></div>
Tamoxifen Gel Effective When Applied to Breast, With Fewer Side Effects Than Oral Tamoxifen1406727/15/2014 1:25:20 PM Releases/AllItems.aspx566False2014-07-15T04:05:00Z<div class="ExternalClass0406D2C0B89C4EBE90813EB8FE84C468"><p>PHILADELPHIA — A breakdown product of tamoxifen, 4-OHT, applied as a gel formulation on the breasts of women with ductal carcinoma in situ (DCIS), was as effective in reducing cell proliferation as oral tamoxifen, with fewer side effects compared with oral tamoxifen, according to a study published in <em><a href="http&#58;//" target="_blank">Clinical Cancer Research</a></em>, a journal of the American Association for Cancer Research.&#160;<img src="/PublishingImages/Khan_Seema_150x200.jpg" alt="" style="margin&#58;10px;float&#58;right;vertical-align&#58;auto;" /></p><p>“In this study, we have shown that the gel application of 4-OHT to the skin resulted in high drug levels in the breast but low drugs levels in the circulation. This would maintain the effectiveness of the drug, but minimize the side effects,” said <a title="Seema A. Khan, MD" href="http&#58;//" target="_blank">Seema A. Khan, MD</a>, professor of surgery at <a href="http&#58;//" target="_blank">Northwestern University Feinberg School of Medicine</a> in Chicago, Illinois. </p><p>“Oral tamoxifen is used by some women at high risk for breast cancer to prevent the development of the disease, and our data suggest that gel application of tamoxifen could replace this approach, thus encouraging more women to adhere to preventive therapy,” added Khan.</p><p>Khan and colleagues conducted a randomized, double-blind, placebo-controlled phase II clinical trial to compare the effects of 4-OHT gel applied on the breasts with those of tamoxifen taken orally. They found that after six to 10 weeks of gel application, the reduction in a marker of cell proliferation, Ki-67, in breast tissue was comparable with that of oral tamoxifen taken for a similar period of time. Blood levels of the drug were much lower when applied as a gel, compared with oral tamoxifen, and this reduced hormonal side effects and blood clotting, which are commonly seen among patients treated with oral tamoxifen.</p><p>The researchers randomly assigned 26 women, ages 45 to 86 years, with a diagnosis of estrogen receptor-positive DCIS, to either the 4-OHT gel arm or the oral tamoxifen arm. All patients provided a baseline blood sample and completed the Breast Cancer Prevention Trial Eight Symptom Scale (BESS) questionnaire. For six to 10 weeks prior to surgery, patients in the gel arm applied 1 ml of the gel to the skin of each breast every morning. Patients from the oral tamoxifen arm took a 20 mg tamoxifen capsule every day.</p><p>One ml of the gel contained 2 mg of 4-OHT.</p><p>All patients provided a second blood sample at the end of the study, and completed the BESS questionnaire at 15 days, at the end of the study, and during the post-surgery visit.</p><p>The researchers found that equal amounts of 4-OHT were present in the breast tissue of patients from both the gel and oral tamoxifen arms (5.8 ng/g versus 5.4 ng/g, respectively) collected during surgery, but the levels of 4-OHT in the blood of patients from the gel arm was 5.5-fold lower than it was in the blood of those from the oral tamoxifen arm (0.2 ng/ml versus 1.1ng/ml, respectively).</p><p>The substantial reduction in the levels of 4-OHT in the blood of patients who administered the gel correlated with a reduction in factors that cause blood clots.</p><p>“Tamoxifen has to be broken down by the liver to its active components, which include 4-OHT. In this process, harmful side effects can also arise, such as the activation of proteins that cause blood clots. Because the liver metabolism step is eliminated when the 4-OHT gel is directly applied to breast skin, the harmful effect of increasing the risk for blood clots should also be eliminated,” explained Khan.</p><p>Based on the BESS questionnaire, however, patients from the gel arm had no significant improvement in vaginal symptoms, gastrointestinal symptoms, or hot flashes and sweats, compared with those from the oral tamoxifen arm. </p><p>“We are making rapid advances in improving the efficacy and safety of drugs, but ultimately no progress is possible without public support,” said Khan. “I would like to thank the women who participated in our study. I also ask my compatriots to please consider participation in a research study when the opportunity arises, and support federal funding of biomedical research.”</p><p>This study was funded by the National Institutes of Health and BHR Pharma LLC. Khan declares no conflicts of interest.</p></div>
Cancer Today Summer Issue Addresses Diabetes-Cancer Comorbidity and Spirituality in Cancer Treatment1305947/10/2014 3:48:17 PM30 Releases/AllItems.aspx565False2014-07-10T16:00:00Z<div class="ExternalClass2C96A9EA1AB54F48A4893B729ACBB7E8"><p>PHILADELPHIA — The Summer 2014 issue of <em><a target="_blank" href="http&#58;//">Cancer Today</a></em>, a publication of the American Association for Cancer Research (AACR), features stories on the challenge of facing both cancer and diabetes, incorporating spirituality into cancer patients’ care, and how Ed Bradley of <em>60 Minutes</em> faced leukemia.</p><p>Published quarterly by the AACR, <em>Cancer Today </em>is an authoritative resource for cancer patients, survivors, and their family members and friends. In every issue,<em> Cancer Today </em>offers information and inspiration to help readers face the challenges of diagnosis, treatment, survivorship, and caregiving.</p><p>This issue of <em>Cancer Today </em>includes “<a target="_blank" href="http&#58;//">Cancer and Diabetes&#58; A Balancing Act</a>.” People with type 2 diabetes are at greater risk for being diagnosed with cancer, and having both conditions complicates treatment for each one. “<a target="_blank" href="http&#58;//">A New Look at Spirituality</a>” shows how caring for cancer patients’ spiritual needs is playing a greater role in treatment. “<a target="_blank" href="http&#58;//">Shining a Light</a>” reviews Ed Bradley’s life and the leukemia that he kept largely private.</p><p>Also, <em>Cancer Today </em>tells the <a target="_blank" href="http&#58;//">story of John and Pat Curry</a>, who opened a coffee shop in Augusta, Georgia, in the midst of John’s colorectal cancer diagnosis and treatment.</p><p>To read these stories and others, go to <em><a target="_blank" href="http&#58;//">Cancer Today</a></em>, or follow the magazine on <a target="_blank" href="https&#58;//">Facebook</a> and <a target="_blank" href="https&#58;//">Twitter</a>. </p><p><em>Cancer Today </em>also publishes a free monthly <a target="_blank" href="http&#58;//">e-newsletter</a>, which contains links to web exclusives, information about events and resources, and highlights from new issues.</p><p>Media are welcome to use information from <em>Cancer Today</em>; however, we ask that you cite the source.​</p></div>
First AACR-Leonard Family Foundation Fellowship to Support Work on Triple-negative Breast Cancer1225857/7/2014 2:21:09 PM44 Releases/AllItems.aspx564False2014-07-07T14:00:00Z<div class="ExternalClass9B87F51EE4F8400B84F4CD623F9DB8B2"><p>PHILADELPHIA — The American Association for Cancer Research (AACR) congratulates&#160;Sara Catherine Hanna, PhD, postdoctoral research fellow at the University of North Carolina at Chapel Hill, as the first recipient of the AACR-John and Elizabeth Leonard Family Foundation Basic Cancer Research Fellowship, which will support her research on triple-negative breast cancer (TNBC). <br>&#160;<br>The $50,000 grant is expected to be offered annually for postdoctoral scientists engaged in basic cancer research under an experienced mentor. The program is funded by the <a href="http&#58;//" target="_blank">John and Elizabeth Leonard Family Foundation</a>, which was created by biotechnology industry veteran and philanthropist John Leonard, PhD, and his wife, Elizabeth. Leonard is a member of the board of trustees of the AACR Foundation for the Prevention and Cure of Cancer. </p><p>Hanna received her doctorate in genetics and molecular biology from the University of North Carolina at Chapel Hill in 2013. She currently works there in the laboratory of Gary L. Johnson, PhD, Kenan distinguished professor and chair of the Department of Pharmacology, who will serve as her mentor. Johnson is also a member of the UNC Lineberger Comprehensive Cancer Center and co-director of the cancer center’s program in molecular therapeutics. </p><p>Breast cancers are generally divided into subtypes based on the receptors found within the tumor. The most successful treatments for breast cancer use these receptors to attack the tumor. Unfortunately, treatments which target specific receptors are not available for patients with TNBC. Furthermore, TNBC patients who do not respond to initial therapy have worse overall survival compared with non-TNBC patients. There is a critical need to understand and identify the changes in the triple-negative tumors which enable these types of tumors to remain resistant to treatment.</p><p>Hanna’s project, titled “Kinome dynamics in chemo-sensitive and -insensitive breast cancer,” will focus on kinases, a large family of proteins that regulate cell growth and survival, and that are often mutated in cancers. Kinases appear important for the response to chemotherapy, and many have been successfully targeted in cancers. Hanna will examine the molecular profile of the kinome, the full complement of kinases, in tumor samples from TNBC patients who responded to chemotherapy, compared with those who were resistant to the treatment. She will examine mutations in kinase genes, as well as expression levels and enzymatic activity, to identify molecular signatures that can predict the best treatment for TNBC. In addition, she will use mouse models to further examine the differences in the molecular signatures between chemotherapy-responsive and -resistant tumors.</p><p>The data generated from the first two parts of the study may provide kinome signatures to help identify which chemotherapies may work best for treating TNBC. Hanna will use cell lines and mouse models to test how well these signatures predict the best treatment for TNBC. Ultimately, Hanna hopes to be able to predict which kinase inhibitors can be used in combination with chemotherapy to give better treatment options to patients with TNBC.</p></div>
New Approach Identifies Cancer Mutations as Targets of Effective Melanoma Immunotherapy1102227/1/2014 2:00:08 PM20 Releases/AllItems.aspx563False2014-07-01T04:05:00Z<div class="ExternalClass62C4E1909F634F54AAEE0416CAFED529"><p>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 <em><a href="http&#58;//" target="_blank">Clinical Cancer Research</a></em>, a journal of the American Association for Cancer Research. <img alt="Steven A. Rosenberg, MD, PhD" src="/PublishingImages/Rosenberg_Steven_150x200.jpg" style="margin&#58;10px;float&#58;right;vertical-align&#58;auto;" /></p><p>“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 <a href="http&#58;//" target="_blank">Steven A. Rosenberg, MD, PhD</a>, chief of surgery at the <a href="http&#58;//" target="_blank">National Cancer Institute</a> (NCI) in Bethesda, Maryland. “The two targets identified in this study play important roles in cancer cell proliferation.</p><p>“Immunotherapy has the potential to successfully treat cancer by targeting tumor mutations. We’ve moved one step closer because of this study,” Rosenberg added.</p><p>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.</p><p>“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.</p><p>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.</p><p>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.</p><p>Using cDNA library screening, the researchers identified three novel nonmutated tumor targets, and four previously known non-mutated tumor targets.</p><p>Using tandem minigene library screening, they identified two novel mutated tumor targets, KIF2C and POLA2, which play important roles in cell proliferation.</p><p>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.</p><p>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.​</p></div>
American Association for Cancer Research Debuts New Brand Identity1099267/1/2014 1:20:59 PM16 Releases/AllItems.aspx562False2014-07-01T04:00:00ZUpdated look reflects a more public-facing direction for the AACR to raise awareness and support for cancer research<div class="ExternalClass3047AF7514344064ACEC46803AEE0315"><p>&#160;</p><p><img src="/PublishingImages/aacr_logo070114.jpg" alt="" style="margin&#58;5px;" />&#160;</p><p>PHILADELPHIA — The American Association for Cancer Research (AACR), the world's largest scientific organization dedicated to accelerating advances against cancer, unveiled a new <a href="http&#58;//;" target="_blank">logo and brand identity</a> 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.</p><p>The new identity begins its official launch today on the AACR's new website, <a href="/" target="_blank"></a>, with a robust public awareness campaign to follow in the fall of 2014 through the AACR Foundation.</p><p>&quot;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,&quot; said Margaret Foti, PhD, MD (h.c.), chief executive officer of the AACR. &quot;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.&quot;</p><p>The new logo is designed to be distinctive and bold, according to Foti. &quot;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,&quot; said Foti.</p><p>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.</p><p>&quot;This is a very exciting period of growth and new direction for the AACR,&quot; said Foti. &quot;The way we present ourselves to all of our constituencies now reflects this dynamism.&quot;</p><p>To view the new logo and brand identity of the AACR, visit the organization's website at <a href="/" target="_blank"></a>.</p></div>
Continued Use of Low-dose Aspirin May Lower Pancreatic Cancer Risk1088656/30/2014 8:30:18 PM20 Releases/AllItems.aspx561False2014-06-26T04:00:00Z<div class="ExternalClass0D5B241BE9FC4966B00E493CC01221EF"><p>​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 <em><a title="Cancer Epidemiology, Biomarkers &amp; Prevention" target="_blank" href="http&#58;//">Cancer Epidemiology, Biomarkers &amp; Prevention</a></em>, a journal of the <a href="/">American Association for Cancer Research</a>.<br><br>“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 <a target="_blank" href="http&#58;//">Harvey A. Risch, MD, PhD</a>, professor of epidemiology in the Department of Chronic Disease Epidemiology at the <a href="http&#58;//" target="_blank">Yale School of Public Health</a> 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.”<br><br>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.<br><br>“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.<br><br>“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.<br><br>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.<br><br>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.<br><br>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.<br><br>Of the participants, 96 percent of low-dose aspirin users and 92 percent of regular-dose aspirin users reported daily aspirin use.<br><br>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. <br><br>“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.<br><br>“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.”<br>&#160;<br>This study was funded by the National Cancer Institute. Risch declares no conflicts of interest.<br></p></div>
Combination Tumor Imaging Can Distinguish Malignant and Benign Breast Tumors, Help Avoid Unnecessary Biopsies52756/25/2014 6:40:37 PM Releases/AllItems.aspx560False2014-06-24T04:00:00Z<div class="ExternalClass383C00F52D09410999BA0C03ACA3B916"><p>​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 <em><a href="http&#58;//" target="_blank">Clinical Cancer Research</a></em>, a journal of the American Association for Cancer Research.&#160;</p><p>“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 <a href="http&#58;//">Medical University of Vienna </a>in Austria.</p><p>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.</p><p>“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.</p><p>“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.</p><p>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.</p><p>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.</p><p>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.<br>&#160;<br>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.)</p><p>“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.”</p><p>MP 18FDG PET-MRI allowed tumor imaging by four parameters&#58; DCE-MRI, DWI, 3D 1H-MRSI, and 18FDG-PET.</p><p>Thomas Helbich, MD, MBA, is the senior author of this study and head of this study group.</p><p>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.</p></div>
A Vaccine May Cause Pancreatic Cancer to Respond to Immunotherapy52737/1/2014 9:07:55 PM26 Releases/AllItems.aspx559False2014-06-18T04:00:00Z<div class="ExternalClass3A00D4393E714F85AD4B108EF3BAB3F0"><p>​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 <a href="http&#58;//" target="_blank"><em>Cancer Immunology Research</em></a>, a journal of the American Association for Cancer Research (produced in collaboration with the Cancer Research Institute). <img title="Lei Zheng, MD, PhD" alt="Lei Zheng, MD, PhD" src="/PublishingImages/Zheng_Lei_150x200.jpg" border="0" style="margin&#58;10px;width&#58;150px;float&#58;right;vertical-align&#58;auto;" /><br><br>“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 <a href="http&#58;//;appRedirRef=http&#58;//" target="_blank">Lei Zheng, MD, PhD</a>, assistant professor of oncology and surgery at the <a href="http&#58;//" target="_blank">Sidney Kimmel Comprehensive Cancer Center</a> and the <a href="http&#58;//" target="_blank">Skip Viragh Center for Pancreatic Cancer Research and Clinical Care</a> at the Johns Hopkins University School of Medicine in Baltimore. <br><br>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.<br><br>“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.<br><br>“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.<br><br>Between 2008 and 2012, Zheng and colleagues enrolled 59 patients with PDAC to this study and randomized them among three arms&#58; 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. <br><br>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.<br><br>In addition to tumor samples from the 39 patients, the researchers used, for the comparative analyses, tumor samples from 58 patients from other studies&#58; Four were unvaccinated patients and 54 were patients whose tumor samples were collected prior to vaccination. <br><br>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. <br><br>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.<br><br>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.<br><br>“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.<br><br>“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.”<br><br>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.</p></div>