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Immune Therapy to Fight Cancer

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Topic: Immune Therapy to Fight Cancer
Posted By: 123Donna
Subject: Immune Therapy to Fight Cancer
Date Posted: Feb 21 2012 at 8:43pm
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Clinical Trials Network Aims to Strengthen Cancer Immunotherapy Pipeline

Later this year, the first clinical trials will be launched under a new NCI-funded initiative to spur the development of cancer treatments that work by revving up the immune system's response to tumors. The  http://citninfo.org/index.html - Cancer Immunotherapy Trials Network   http://www.cancer.gov/global/web/policies/page8">Exit Disclaimer  (CITN) includes the foremost researchers in cancer immunotherapy from  http://www.cancer.gov/ncicancerbulletin/040511/page11#b - 27 top U.S. cancer centers and universities who are working collectively to identify promising agents and to formulate and run the trials in which they will be tested.

The first  http://www.cancer.gov/dictionary?CdrID=45729 - immunotherapy  agents to enter CITN trials have been selected, and several trials are moving closer to launch. The first two agents,  http://www.cancer.gov/drugdictionary?CdrID=661035 - interleukin-15 (IL-15) and  http://www.cancer.gov/drugdictionary?CdrID=588974 - CP-870,893 , were selected "based on broad consensus and the field's collective experience and 'wisdom,'" explained Dr. Martin A. "Mac" Cheever, the CITN's principal investigator and director of the CITN Central Operating and Statistical Center (COSC), located at the Fred Hutchinson Cancer Research Center in Seattle.

All CITN trials will be  http://www.cancer.gov/dictionary?CdrID=45830 - phase I  or  http://www.cancer.gov/dictionary?CdrID=45831 - phase II  trials. The network's aim is to establish a pipeline of agents to test in the large  http://www.cancer.gov/dictionary?CdrID=45833 - phase III  trials that ultimately determine whether a new treatment will make it to the clinic, said Dr. Cheever, who, along with co-investigator Dr. Kim Margolin, runs the network's day-to-day operations. Correlative science studies, such as those that look for  http://www.cancer.gov/dictionary?CdrID=45618 - biomarkers  that indicate which patients are likely to respond to a treatment and that assess the extent to which treatments stimulate an immune response, will be built into the trials. These studies will be performed under the direction of Dr. Cheever's other co-investigator, Dr. Mary L. "Nora" Disis.

"The goal," Dr. Cheever explained, "is to design trials that can quickly demonstrate proof of concept and patient benefit, ultimately helping to define a path toward regulatory approval."

The Field Comes Together

The concept of using a patient's own immune system to destroy tumors has enticed researchers for decades. Until quite recently, however, regimens focused on boosting patient immune responses to their own cancers, although effective in some patients, have failed to produce many broadly effective treatments. (For years, blood and bone marrow transplants, which restore or replace patients' immune systems, have been highly effective treatments for leukemia and lymphoma, and some monoclonal antibodies, such as  http://www.cancer.gov/cancertopics/druginfo/trastuzumab - trastuzumab  [Herceptin], are believed to work, in part, by stimulating an antitumor immune response.)

But a confluence of events has propelled the field forward, said Dr. William Merritt of NCI's  http://dctd.cancer.gov/ - Division of Cancer Treatment and Diagnosis  (DCTD) and NCI program director for the CITN. Chief among them has been the "vastly improved understanding of tumor immunology and the number of agents known to modify the immune response to tumors," Dr. Merritt said.

A major tipping point was the first NCI-sponsored Immunotherapy Agents Workshop, held in 2007, which brought together leading cancer immunologists to identify the most promising immunotherapy agents for further study and development. From more than 120 candidates, 20 agents were chosen. NCI held additional workshops to help further prioritize agents for development, with an emphasis placed on agents with the greatest potential for broad usage by multiple investigators in different regimens, Dr. Cheever explained.

"Everything that's happened progressed from that first workshop," Dr. Cheever added.

Not long after the series of prioritization workshops, a group of immunotherapy researchers approached then-NCI Director Dr. John E. Niederhuber and urged him to increase the institute's support for efforts to facilitate the development of high-priority agents, Dr. Merritt recalled. Dr. Niederhuber and DCTD leaders agreed, and the CITN concept was born.

Cancer Immunotherapy Trials Network logo

In addition, the Food and Drug Administration last year approved two cancer immunotherapies: ipilimumab (Yervoy) http://www.cancer.gov/ncicancerbulletin/040511/page8 - to treat advanced melanoma  and sipuleucel-T (Provenge) for the  http://www.cancer.gov/ncicancerbulletin/050410/page2 - treatment of advanced prostate cancer .

The impact of those approvals was enormous, said Dr. Jedd Wolchok, a CITN investigator at Memorial Sloan-Kettering Cancer Center. "For pharmaceutical companies and the industry to see a successful immunotherapy that can be administered in a doctor's office has really changed the field," Dr. Wolchok said.

Researchers have historically had difficulty gaining access to the diverse array of investigational immunotherapy agents that have shown significant promise in laboratory testing as well as early phase clinical trials. In some cases, the company that developed an agent prioritized its development for a disease other than cancer, or the agent needed to be developed in combination with other agents as part of a multi-component regimen.

Availability has "definitely been a major bottleneck," said Dr. Thomas Gajewski, a CITN investigator at the University of Chicago Medical Center. 

That is now beginning to change. Numerous companies are more interested in making agents available for study and developing new investigational immunotherapy agents, Dr. Wolchok said. Several are even establishing immuno-oncology departments.

"And we, as a community of cancer immunotherapy investigators, need to be prepared to help them test [these agents] in a thoughtful way," he continued. "And that's where the CITN can play a major role."

Collaboration Pushing Science Forward

Having a network of investigators and centers "means that we can initiate trials in a timely way," Dr. Merritt explained. "We don't have to wait for individual grants to get funded, with  [researchers] doing their own trials at their own institutions." And having multiple centers involved in each trial, he added, will significantly improve how quickly trials can accrue patients and be completed.

But the potential benefits go well beyond speedier trials, Dr. Gajewski stressed.

"With a network, data are shared, and data management and statistical analysis are all uniform," he explained. "Before data are published, we'll all be exchanging this information, so the cross-fertilization potential will be huge. Ideas will move much more readily among investigators and among projects."

The CITN has benefitted greatly from the support of staff from another NIH-funded clinical trials initiative run out of Fred Hutchinson, the  http://www.hvtn.org/ - HIV Vaccine Trials Network   http://www.cancer.gov/global/web/policies/page8">Exit Disclaimer  supported by the National Institute of Allergy and Infectious Diseases, Dr. Cheever noted. And potential research collaborations are already being discussed between the CITN and a similar international cancer immunotherapy trials network led by Dr. Wolchok, the Cancer Vaccine Collaborative.

The CITN is funded for 5 years, Dr. Cheever said, and he has had encouraging discussions about obtaining additional funding from industry and philanthropy groups.

Getting the initial trials up and going is an important step, Dr. Merritt said. But it's just the beginning. "Several CITN working groups and its steering committee are now discussing the trial concepts for the next group of agents to move forward," he noted. "I'm very encouraged by the progress so far."

http://www.cancer.gov/ncicancerbulletin/bios/phillips - Carmen Phillips

The First Agents

Numerous types of immunotherapeutic agents have been developed, including  http://www.cancer.gov/dictionary?CdrID=44928 - T-cell  and  http://www.cancer.gov/dictionary?CdrID=44439 - NK-cell   http://www.cancer.gov/dictionary?CdrID=45705 - growth factors  like  http://www.cancer.gov/drugdictionary?CdrID=661035 - IL-15 , others that stimulate T cells or activate  http://www.cancer.gov/dictionary?CdrID=44948 - dendritic cells , so-called immune checkpoint inhibitors like ipilimumab, and others that inhibit or neutralize factors secreted by tumors that suppress the immune system.

The first two agents to be tested in CITN-led trials, selected from the 20 identified in the 2007 workshop, will be IL-15 and a dendritic cell-activating   http://www.cancer.gov/dictionary?CdrID=46066 - monoclonal antibody  called  http://www.cancer.gov/drugdictionary?CdrID=588974 - CP-870,893 .

The first human trial of IL-15 was  http://www.cancer.gov/ncicancerbulletin/012412/page8 - recently launched  at NCI by Dr. Thomas Waldmann, who co-discovered IL-15 nearly 18 years ago, and Dr. Kevin Conlon. For these first trials, NCI is manufacturing IL-15 at its drug production facility on the  http://web.ncifcrf.gov/ - NCI-Frederick  campus. The CITN trial of IL-15 is separate from Dr. Waldmann and Dr. Conlon's trial, but CITN investigators are working closely with Dr. Waldmann on IL-15's development, Dr. Cheever noted.

The Pfizer-developed CP-870,893—which targets the CD40  http://www.cancer.gov/dictionary?CdrID=46086 - antigen  on certain immune cells—has already http://www.cancer.gov/ncicancerbulletin/040511/page3#d - shown efficacy  in a small phase I trial of patients with advanced pancreatic cancer. The CITN trial, to be led by Dr. Robert Vonderheide of the University of Pennsylvania, will test the CD40-targeted antibody as a presurgical treatment in patients with operable pancreatic cancer.

Planning and negotiations are underway to test several other treatment strategies, including the cytokine http://www.cancer.gov/drugdictionary?CdrID=305941 - IL-7  and an agent in development that targets the immune checkpoint protein PD-1 on the surface of certain immune cells.

http://www.cancer.gov/ncicancerbulletin/022112/page6 - http://www.cancer.gov/ncicancerbulletin/022112/page6



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15




Replies:
Posted By: christina1961
Date Posted: Feb 21 2012 at 8:51pm
Smile
Very good news!


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2.5 cm TNBC, BRCA-, diag. 2/11, neoadj chemotherapy, uni MX, y2cm,2/16 nodes, RCBII, tumor retested 5-10%ER+,PR-,Her2-, rads, clin trial eribulin 10/11-2/12, tamox.


Posted By: 123Donna
Date Posted: May 01 2012 at 3:55pm

Pitt aims to prove therapy can offer new cancer hope

David Templeton
Pittsburgh Post-Gazette

04-27-12

April 27--A human clinical trial under way at UPMC's Hillman Cancer Center in Shadyside will help determine whether a combination of approved drugs based on a new theory of cancer can "revolutionize cancer therapy."

That's the explanation of lead researcher Michael T. Lotze, who says his team has combined interleukin 2 (IL-2) with hydroxychloroquine in a new therapy designed to be more effective and less toxic in curing cancer than IL-2 alone.

The new cancer theory, how the two drugs work in tandem and how the treatment works involve complicated science. The Pitt team starts with IL-2, a drug that strengthens the immune response to cancer but doesn't work in the majority of patients, in part, due to severe toxicity. It then adds an inexpensive drug, hydroxychloroquine, to serve a different role -- to reduce the cancer drug's toxicity and increase its cancer-killing efficiency.

IL-2, a hormone that promotes immune T cells that fight infections and cancer at local sites, is considered the only cancer cure available. But it's effective in only 10 percent of the patients with renal-cell (kidney) cancer and melanoma who qualify for the treatment.

One chief concern is IL-2's toxicity in high doses sent bodywide to fight cancer. The drug causes healthy tissue and organ cells to begin consuming themselves in a process known as autophagy -- Greek for "self-eating" -- that leads to vascular leakage among other serious side effects.

But a new Pitt theory about cancer says autophagy also helps explain how cancer cells produce tumors.

Dr. Lotze, professor of surgery, immunology and bioengineering at the University of Pittsburgh School of Medicine, said cancer patients who undergo IL-2 immunotherapy experience extreme influenza-like symptoms that many can't tolerate for the few days they receive it. But the oral medication hydroxychloroquine, originally used to treat patients with malaria and now used to treat patients with systemic lupus erythematosus, rheumatoid arthritis, HIV and other diseases, reduces IL-2 toxicity by inhibiting autophagy without hindering the drug assault on cancer.

The drug combination in mice with cancer proved to be "dramatically more effective" than IL-2 alone. Published April 3 in Cancer Research, the study was performed by Xiaoyan Liang, a UPMC scientist on the Lotze team at the cancer center.

Clinical-trial success could increase IL-2's use in treating kidney cancer and melanoma and expand that use to other major cancers.

With the two drugs already approved for use by the U.S. Food and Drug Administration, Pitt's Cancer Institute team hopes to test the new drug regimen on 60 renal-cell (kidney) patients. Those interested in participating should call 877-470-7241.

Michael Wong, professor of medicine at the Norris Comprehensive Cancer Center at the University of Southern California, said he's familiar with the study but was not involved in it.

The key problem with IL-2, he said, is that patients must be admitted to a hospital because of blood pressure problems and vascular leakage it causes, along with impacts on the liver, kidneys and other organs.

"The holy grail," he said, would be reductions in IL-2's toxic side effects so more patients could undergo the treatment.

"One in 10 people have a tremendous response from IL-2 -- a complete response where the tumor melts away," he said, describing it as a cure in that small percentage. But the1-in-10 success rate in those able to undergo the therapy has not budged for many years.

"In the Lotze trial, if they can get more patients in and move the needle to 2 out of 10 or 3 out of 10 -- if it truly works -- it's going to be dramatic," Dr. Wong said. "Any improvement would be mind-boggling because we've been stuck here for quite a while."

The traditional theory of cancer says a genetic mutation causes uncontrolled cell growth. But the Pitt team says cancer isn't just a disorder of cell growth, but just as much a disorder in cell death.

Rather than die in an organized, natural way through a process known as "apoptosis," as occurs with normal cells, a genetic mutation causes cancer cells to die through the process of necrosis following autophagy. Dr. Lotze describes necrosis as "a terrible, horrible, screaming-out-loud, blood-in-the-streets type of death."

In the process, cancer cells consume themselves and shed cellular parts into the tissue to keep other cancer cells alive. It also provides biological infrastructure to sustain tumor growth.

"Tumors just want to die," Dr. Lotze said. But those dying cancer cells promote autophagy and set the stage for their survival by recruiting immune cells and new cells to develop blood vessels. Those vessels help sustain the cancer cells that otherwise would die.

"What's new is our understanding of autophagy," he said. "Our innovation was to marry tumor immunology to autophagy."

The Pitt team's goal is to kill cancer cells naturally through immunology rather than allow autophagy to continue. Even with its toxic side effects, IL-2 remains "the closest to a [cancer] cure that we have," Dr. Lotze said.

Traditional chemotherapy, which can reduce tumor size and knock back cancer growth temporarily, also can promote rather than halt autophagy, which allows cancer to return with a vengeance, he said.

The Pitt team's theory about autophagy's role in cancer "is a novel one" that could make scientists "rethink what holds true" with cancer, Dr. Wong said. "It can shake the ground you stand on, and this is the first step in that direction."

If the clinical trial shows that the combination drug treatment is less toxic and more effective, Dr. Lotze said, "We think this can potentially revolutionize cancer therapy."

David Templeton: dtempleton@post-gazette.com or 412-263-1578.

___

(c)2012 the Pittsburgh Post-Gazette

Visit the Pittsburgh Post-Gazette at www.post-gazette.com

Distributed by MCT Information Services

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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jun 03 2012 at 7:01pm
While not breast cancer related, promising research on immunotherapy clinical trials.

Cancer therapy that boosts immune system ready for wider testing

Two clinical trials led by Johns Hopkins Kimmel Cancer Center researchers in collaboration with other medical centers, testing experimental drugs aimed at restoring the immune system’s ability to spot and attack cancer, have shown promising early results in patients with advanced non-small cell lung cancer, melanoma, and kidney cancer. More than 500 patients were treated in the studies of two drugs that target the same immune-suppressive pathway, and the investigators say there is enough evidence to support wider testing in larger groups of patients

http://www.breakthroughdigest.com/medical-news/cancer-therapy-that-boosts-immune-system-ready-for-wider-testing/ - http://www.breakthroughdigest.com/medical-news/cancer-therapy-that-boosts-immune-system-ready-for-wider-testing/
.



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jun 08 2012 at 9:31pm
New cancer therapy liberates captive cancer-fighting T-cells
http://www.usatoday.com/news/health/story/2012-06-01/liberating-t-cells-cancer/55335158/1?loc=interstitialskip - http://www.usatoday.com/news/health/story/2012-06-01/liberating-t-cells-cancer/55335158/1?loc=interstitialskip


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jun 16 2012 at 3:45pm

Drug Helps Immune System Fight Cancer, Study Says

William Weir, The Hartford Courant, Conn. 
The Hartford Courant, Connecticut

06-04-12

June 02--NEW HAVEN -- A study conducted in part by researchers at the Yale School of Medicine suggests that a new drug that bolsters the immune system can shrink tumors in certain cancers -- including lung cancer, which has been resistant to treatment.

The tumors of about one-fourth of the study's 300 patients with non-small cell lung cancer, renal cell cancer and advanced melanoma significantly decreased in size after the patients were given the drug.

The study -- which was also authored by researchers from Johns Hopkins University, Harvard University, Bristol-Myers Squibb and other institutions -- appears Saturday in the New England Journal of Medicine. Several of the researchers are also presenting their findings at the annual meeting of the American Society of Clinical Oncology in Chicago this weekend.

The drug, known as BMS-936558, was developed by Bristol-Myers Squibb and is still in the study phase.

The drug is an antibody designed to restore the functions of lymphocyte cells, known as T-cells, and to foil tumors' ability to fight off the immune system.

"What happens is that the T-cells look for things that shouldn't be in the body," said co-author Scott Gettinger, associate professor of medicine at Yale.

But sometimes, Gettinger said, "there's a communication between the T-cell and the tumor, which tells the T-cell to not attack it." The drug, he said, "binds to the T-cell, which doesn't allow the negative communication."

Tumors shrank by at least 30 percent in 28 percent of the melanoma patients; a slightly smaller percentage of renal cancer patients had similar reductions in tumors. And 18 percent of the lung cancer patients had tumor reductions of 30 percent or more.

Gettinger said the progress made in the lung cancer tumors was most surprising.

"Immunotherapy has been tried for a long time in lung cancer in prior studies and it never amounted to much," he said.

Gettinger said the drug has to go through the U.S. Food and Drug Administration approval process so it could be years before it is widely available.

___

(c)2012 The Hartford Courant (Hartford, Conn.)

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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jan 03 2013 at 8:38pm

Revolutionary techniques could help harness patients’ own immune cells to fight disease


The human body contains immune cells programmed to fight cancer and viral infections, but they often have short lifespans and are not numerous enough to overcome attacks by particularly aggressive malignancies or invasions. Now researchers reporting in two separate papers in the January 4th issue of the Cell Press journal Cell Stem Cell used stem cell technology to successfully regenerate patients’ immune cells, creating large numbers that were long-lived and could recognize their specified targets: HIV-infected cells in one case and cancer cells in the other. The findings could help in the development of strategies to rejuvenate patients’ exhausted immune responses.

The techniques the groups employed involved using known factors to revert mature immune T cells into induced pluripotent stem cells (iPSCs), which can differentiate into virtually any of the body’s different cell types. The researchers then expanded these iPSCs and later coaxed them to redifferentiate back into T cells. Importantly, the newly made T cells were “rejuvenated” with increased growth potential and lifespan, while retaining their original ability to target cancer and HIV-infected cells. These findings suggest that manipulating T cells using iPSC techniques could be useful for future development of more effective immune therapies.

In one study, investigators used T cells from an HIV-infected patient. The redifferentiated cells they generated had an unlimited lifespan and contained long telomeres, or caps, on the ends of their chromosomes, which protect cells from aging. This is significant because normal aging of T cells limits their expansion, making them inefficient as therapies. “The system we established provides ‘young and active’ T cells for adoptive immunotherapy against viral infection or cancers,” says senior author Dr. Hiromitsu Nakauchi, of the University of Tokyo.

The other research team focused on T cells from a patient with malignant melanoma. The redifferentiated cells they created recognized the protein MART-1, which is commonly expressed on melanoma tumors. “The next step we are going to do is examine whether these regenerated T cells can selectively kill tumor cells but not other healthy tissues. If such cells are developed, these cells might be directly applied to patients,” says senior author Dr. Hiroshi Kawamoto, of the RIKEN Research Center for Allergy and Immunology. “This could be realized in the not-so-distant future.”

###

Nishimura et al.: “Generation of rejuvenated antigen-specific T cells by pluripotency reprogramming and redifferentiation.”

Vizcardo et al.: “Regeneration of human tumor antigen-specific T cells from iPS cells derived from mature CD8+ T cells.”

Contact: Mary Beth OLeary
mailto:moleary@cell.com - moleary@cell.com
617-397-2802

http://www.breakthroughdigest.com/medical-news/revolutionary-techniques-could-help-harness-patients-own-immune-cells-to-fight-disease/ - http://www.breakthroughdigest.com/medical-news/revolutionary-techniques-could-help-harness-patients-own-immune-cells-to-fight-disease/



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jun 24 2013 at 9:06pm

Targeted viral therapy destroys breast cancer stem cells in preclinical experiments


A promising new treatment for breast cancer being developed at Virginia Commonwealth University Massey Cancer Center and the VCU Institute of Molecular Medicine (VIMM) has been shown in cell culture and in animal models to selectively kill cancer stem cells at the original tumor site and in distant metastases with no toxic effects on healthy cells, including normal stem cells. Cancer stem cells are critical to a cancer’s ability to recur following conventional chemotherapies and radiation therapy because they can quickly multiply and establish new tumors that are often therapy resistant.

The study, published in the International Journal of Cancer, focuses on a gene originally cloned in the laboratory of primary investigator Paul B. Fisher, M.Ph., Ph.D. The gene, melanoma differentiation associated gene-7 (mda-7), also known as interleukin (IL)-24, has been shown to directly impact two forms of cell suicide known as apoptosis and toxic autophagy, regulate the development of new blood vessels and also play a role in promoting cancer cell destruction by the immune system. In the present study, the researchers used a recombinant adenovirus vector, an engineered virus with modified genetic material, known as Ad.mda-7 to deliver the mda-7/IL-24 gene with its encoded protein directly to the tumor.

“Therapy with the mda-7/IL-24 gene has been shown to be safe in a phase I clinical trial involving patients with advanced cancers, and prior studies in my laboratory and with collaborators have shown that the gene could also be effective against breast, prostate, lung, colorectal, ovarian, pancreatic and brain cancers,” says Fisher, Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics program at VCU Massey, chairman of VCU School of Medicine’s Department of Human and Molecular Genetics and director of the VCU Institute of Molecular Medicine. “Our study demonstrates that this therapy may someday be an effective way to eradicate both early and advanced stage breast cancer, and could even be used to reduce the risk of cancer recurrence.”

The researchers found that infection of human breast cancer cells with the adenovirus decreased the proliferation of breast cancer stem cells without affecting normal breast stem cells. It was also shown to induce a stress response in the cells that led to apoptosis by disrupting Wnt/B-catenin signaling, a process cells rely upon to transmit signals that initiate biological functions critical to survival. In mouse models, the therapy profoundly inhibited the growth of tumors generated from breast cancer stem cells and also killed cancer cells in distant, uninjected tumors.

Since discovering the mda-7/IL-24 gene, Fisher and his team have worked to develop better ways to deliver it to cancer cells, including two cancer “terminator” viruses known as Ad.5-CTV and Ad.5/3-CTV. Cancer terminator viruses are unique because they are designed to replicate only within cancer cells while delivering immune-modulating and toxic genes such as MDA-7/IL-24. Coupled with a novel stealth delivery technique known as ultrasound-targeted microbubble destruction (UTMD), researchers can now systemically deliver viruses and therapeutic genes and proteins directly to tumors and their surrounding tissue (microenvironment) at both primary and metastatic tumor sites. UTMD uses microscopic, gas-filled bubbles that can be paired with viral therapies, therapeutic genes and proteins, and imaging agents and can then be released in a site and target-specific manner via ultrasound. Fisher and his colleagues are pioneering this approach and have already reported success in experiments utilizing UTMD technology and mda-7/IL-24 gene therapy in prostate and colorectal cancer models.

“We are hopeful that this targeted gene therapy could be safely combined with conventional chemotherapies to significantly improve outcomes for patients with breast cancer and potentially a variety of other cancers,” says Fisher. “When paired with promising new delivery techniques such as UTMD, physicians may one day be able to better target site-specific cancers and also monitor the effectiveness of these types of therapies in real time.”

http://www.breakthroughdigest.com/medical-news/targeted-viral-therapy-destroys-breast-cancer-stem-cells-in-preclinical-experiments/" rel="nofollow - http://www.breakthroughdigest.com/medical-news/targeted-viral-therapy-destroys-breast-cancer-stem-cells-in-preclinical-experiments/



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: denise07
Date Posted: Jun 24 2013 at 10:51pm
Donna,
Thank you so much for this information you are one fighting trooper who has our backs covered.
Love ya,
Denise


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DX Idc 10/07,st2,gr3,2/6 lymphnodes


Posted By: kah
Date Posted: Jun 24 2013 at 11:54pm
Ditto! Thanks Donna!!!


Posted By: 123Donna
Date Posted: Jun 28 2013 at 9:50pm
We'll have to keep an eye on this drug/trial.

http://www.huffingtonpost.com/2013/05/16/mpdl3280a-immunotherapy-drug-cancer_n_3281876.html" rel="nofollow - http://www.huffingtonpost.com/2013/05/16/mpdl3280a-immunotherapy-drug-cancer_n_3281876.html




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jul 03 2013 at 8:51am
This is the clinical trial, Phase 1 for MPDL3280A:

http://clinicaltrials.gov/show/NCT01375842" rel="nofollow - http://clinicaltrials.gov/show/NCT01375842

Engineered Antibody Demonstrated Safety, Efficacy in Wide Range of Advanced Tumors

  • The PD-L1 antibody MPDL3280A displayed antitumor activity across a range of cancer types, including lung, kidney, colon and stomach cancers.
  • MPDL3280A was well tolerated.
  • Phase I study results demonstrated no limiting toxicities.
WASHINGTON, D.C. — The engineered antibody MPDL3280A, which targets a protein called programmed death-ligand 1 (PD-L1), was safe and effective for several cancers, according to phase I study results presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“Our PD-L1 antibody was well tolerated, and there were no limiting toxicities,” said Michael S. Gordon, M.D., research director at Pinnacle Oncology Hematology in Scottsdale, Ariz. “It was active with antitumor activity across a broad range of cancers, and we have developed biomarker tools that we are testing, which may allow us to optimize patient selection for this novel therapy.”

PD-L1, a protein found on the surface of many cancer cells, impairs the immune system’s ability to fight cancer, according to Gordon. 

“PD-L1 is essentially a plug, which inserts into an outlet (PD-1) on the surface of the immune T cells,” Gordon said. “As the T cells come close to the tumor, for example, they are engaged by PD-L1, which inserts into the outlet on the surface of the T cell. That starts a signal inside the T cell that blocks the T cell’s ability to kill the cancer cell.” 

MPDL3280A, a human monoclonal antibody under development by Genentech, a member of the Roche Group, binds to PD-L1 and blocks this action.

Gordon and colleagues administered an escalating intravenous dose of MPDL3280A once every three weeks to 30 patients with a variety of locally advanced or metastatic solid tumors. They escalated the dose from 0.01 mg/kg to as high as 20 mg/kg. The data being presented are the preliminary data from the dose escalation cohorts of the ongoing phase I trial. 

No dose-limiting toxicities or grade 4 adverse events have been reported. “We were able to escalate to the top dose without being limited by any serious side effects,” Gordon said.

“From a therapeutic standpoint, we were able to identify a number of patients with a broad range of diseases, including lung cancer, kidney cancer, colon cancer and stomach cancer, who responded to the treatment,” he said. 

A second protein, called PD-L2, fits into the same T-cell “outlet” as PD-L1, according to Gordon. MPDL3280A is specific for PD-L1; it does not block PD-L2, which is expressed in noncancerous tissues including the lung, he added. 

“One would anticipate, compared with drugs being developed to specifically block the T-cell outlet (PD-1) and, therefore, block the relationship between the outlet and both PD-L1 and PD-L2, that we might see less lung or pulmonary toxicity with MPDL3280A. But we need to conduct larger studies to confirm this.”
http://www.aacr.org/home/public--media/aacr-in-the-news.aspx?d=3059" rel="nofollow - http://www.aacr.org/home/public--media/aacr-in-the-news.aspx?d=3059


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jul 13 2013 at 11:27pm
Could this be what we've been waiting for?  I hope we don't have to wait 5 or 10 years to find out.

Exclusive: Cancer - A cure just got closer thanks to a tiny British company - and the result could change lives of millions

A revolution is brewing on an English business park as scientists harness our natural-born killers – the T cells – to target malign tumours

A single-storey workshop on a nondescript business park in Oxfordshire is not the sort of place where you would expect scientific revolutions to take place. But behind the white-painted walls of this small start-up company, scientists are talking about the impossible – a potential cure for cancer.

For the past 20 years, the former academics who set up Immunocore have worked hard on realising their dream of developing a totally new approach to cancer treatment, and finally it looks as if their endeavours are beginning to pay off. In the past three weeks, the company has signed contracts with two of the biggest players in the pharmaceuticals industry which could lead to hundreds of millions of pounds flowing into the firm's unique research on cancer immunotherapy – using the body's own immune system to fight tumour cells.

Immunocore is probably the only company in the world that has developed a way of harnessing the power of the immune system's natural-born killer cells: the T-cells of the blood which nature has designed over millions of years of evolution to seek out and kill invading pathogens, such as viruses and bacteria. T-cells are not nearly as good at finding and killing cancer cells, but the hard-nosed executives of the drugs industry – who are notoriously cautious when it comes to investments – believe Immunocore may have found a way around this so that cancer patients in future are able to fend off their disease with their own immune defences.

"Immunotherapy is radically different," said Bent Jakobsen, the Danish-born chief scientific officer of Immunocore who started to study T-cells 20 years ago while working at the Medical Research Council's Laboratory of Molecular Biology in Cambridge. "It doesn't do away with the other cancer treatments by any means, but it adds something to the arsenal that has one unique feature – it may have the potency to actually cure cancer," Dr Jakobsen said.

It is this potency that has attracted the attention of Genentech in California, owned by the Swiss giant Roche, and Britain's GlaxoSmithKline. Both companies have independently signed deals with Immunocore that could result in up to half a billion pounds being invested in new cancer treatments based on its unique T-cell therapy.

It is no understatement to say that cancer immunotherapy, or immuno-oncology as it is technically called, represents a sea change in terms of cancer treatment. Cancer in the past has been largely treated by slicing (surgery), poisoning (chemotherapy) or burning (radiotherapy). All are burdened with the inherent problem of how to spare healthy tissue from irreparable damage while ensuring that every cancer cell is killed, deactivated or removed.

Now there is another approach based on the immune system, a complex web of cells, tissues and organs that constantly strive to keep the body free of disease, which almost certainly includes keeping cancerous cells in check.

For many years, scientists have realised that the immune system plays a key role in cancer prevention. There is ample evidence of this, not least from patients who are immune-suppressed in some way – they are more likely than other patients to develop cancer.

The immune system has two basic ways of fighting invading pathogens and the body's own cells that have gone awry. One involves the release of free-floating proteins, or antibodies, that lock on to an invader, triggering other immune cells to come in and sweep them away.

Many organisations have tried to develop anti-cancer treatments based on antibodies, with limited success, Dr Jakobsen said. Part of the problem is that antibodies are not really designed to recognise cells. What Immunocore has done is to build a therapy around the second arm of the immune system, known as cellular immunity, where T-cells seek out and destroy invading pathogens.

"There are a lot of companies working with antibodies but we are virtually the only company in the world that has managed to work with T-cells. It has taken 20 years and from that point we are unique," Dr Jakobsen said.

Immunocore has found a way of designing small protein molecules, which it calls ImmTACs, that effectively act as double-ended glue. At one end they stick to cancer cells, strongly and very specifically, leaving healthy cells untouched. At the other end they stick to T-cells.

The technology is based on the "T-cell receptor", the protein that sticks out of the surface of the T-cell and binds to its enemy target. Immunocore's ImmTACs are effectively independent T-cell receptors that are "bispecific", meaning they bind strongly to cancer cells at one end, and T-cells at the other – so introducing cancer cells to their nemesis.

"What we can do is to use that scaffold of the T-cell receptor to make something that is very good at recognising cancer even if it doesn't exist naturally," said Dr Jakobsen. "Although T-cells are not very keen at recognising cancer, we can force them to do so. The potential you have if you can engineer T-cell receptors is quite enormous. You can find any type of cell and any kind of target. This means the approach can in theory be used against any cancer, whether it is tumours of the prostate, breast, liver or the pancreas.

The key to the success of the technique is being able to distinguish between a cancer cell and a normal, healthy cell. Immunocore's drug does this by recognising small proteins or peptides that stick out from the surface membrane of cancer cells. All cells extrude peptides on their membranes and these peptides act like a shop window, telling scientists what is going on within the cell, and whether it is cancerous or not.

"All these little peptides tell you the story of the cell. The forest of them on the cell surface is a sort of display saying 'I am this kind of cell. This is my identity and this is everything going on inside me'," Dr Jakobsen explained.

Immunocore is building up a database of peptide targets on cancer cells in order to design T-cell receptors that can target them, leaving healthy cells alone and so minimising possible side effects – or that is the hope.

The first phase clinical trial of the company's therapy, carried out on a small number of patients in Britain and the United States with advanced melanoma, has shown that people can tolerate the drug reasonably well and preliminary results suggest there are "early signs of anti-tumour activity", the company said.

A danger with deploying T-cells against cancer is their potency. Yet it is this very potency that it is so exciting because it could lead to a cure for metastatic disease that has spread around the body, Dr Jakobsen said. "You can never make a single-mechanism drug that would come anywhere near a T-cell in terms of its potency.

"If you want to make an impact on cancer you need something that is incredibly potent – but when something goes wrong, it goes badly wrong. I think the honest truth about all cancer treatments is that no matter how much we test and do beforehand, it will continue to go wrong sometimes."

One infamous case of something going disastrously wrong was a clinical trial in 2006 at Northwick Park Hospital in London where scientists were testing a powerful immuno-regulatory drug on six volunteers. All suffered serious side effects caused by the overstimulation of their immune systems.

But Dr Jakobsen said the clinical trial of Immunocore's T-cell drug, as well as future trials, are inherently safe because they are based on incremental rises in dose. All indications suggest it will lead to the expected breakthrough.

He added: "All the pharma companies have come to the realisation that immunotherapy may hold the ultimate key to cancer; it is the missing link in cancer treatment that can give cures."

"They have seen this technology develop. It has come over the mountain top, if you like. With our melanoma trial they have seen it is safe – and it is working."

T-cell therapy

Using the body's immune system to fight cancer is one of the most promising areas of therapy, and could prove particularly helpful in the treatment of metastatic disease, when the cancer has spread from its original site.

The immune system is complex and is composed of many kinds of cells, proteins and chemical messengers that modulate how it works. Scientists are working on ways of exploiting the immune defences to recognise and eliminate cells that have become cancerous.

One of the most interesting examples is ipilimumab, a "monoclonal antibody" made by Bristol-Myers-Squib. It recognises and binds to a molecule, called CTLA-4, which is found on the T-cells of the immune system. CTLA-4 normally keeps T-cells from proliferating, but in the presence of ipilimumab, it becomes blocked, allowing T-cells to increase in numbers, so leading them to attack cancer cells.

Other drugs based on monoclonal antibodies are designed to attack tumours more directly. When they bind to a cancerous cell, it serves as a signal for other cells of the immune system to come in and sweep the cancer cells away.

The trouble is that cancer cells are notoriously mutational. Eliminating 99.9 per cent of cancer cells in a patient may be an improvement, but it still leaves 0.1 per cent that could "escape".

One hope of using T-cells, is that this possibility of escape is narrowed down, or even eliminated. Of course, these are still early days. This is only just beginning to go through the first clinical trials. It could take five or 10 years before we know whether or not they work.

http://www.independent.co.uk/news/science/exclusive-cancer--a-cure-just-got-closer-thanks-to-a-tiny-british-company--and-the-result-could-change-lives-of-millions-8707590.html" rel="nofollow - http://www.independent.co.uk/news/science/exclusive-cancer--a-cure-just-got-closer-thanks-to-a-tiny-british-company--and-the-result-could-change-lives-of-millions-8707590.html



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Oct 01 2013 at 12:36pm
Another Immunotherapy drug trial to keep our eye on.


Scancell reports progress across a number of trials

Scancell, which develops novel immunotherapies for the treatment of  http://www.sharecast.com/news/scancell-reports-progress-across-a-number-of-trials/21194198.html#" rel="nofollow - , on Tuesday revealed that four out of the six evaluable patients treated with either the 2mg or 4mg dose of its SCIB1 drug still remain alive.

It said the mean survival time in this group of five Stage IV and one Stage IIIb patients is currently 21 months from trial entry.

As a result of the positive developments and minimal  http://www.sharecast.com/news/scancell-reports-progress-across-a-number-of-trials/21194198.html#" rel="nofollow -  seen with the 4mg dose, Scancell has initiated evaluation of an 8mg dose in up to six patients with measurable tumours, and is currently seeking the appropriate regulatory approval to treat a further 10 patients.

The group also reported that planning is underway for the preclinical and clinical development of SCMod1 as an immunotherapeutic, provisionally for the treatment of triple-negative breast cancer, ovarian and endometrial cancers. First-in-man clinical studies are scheduled to start in 2016.
http://www.sharecast.com/news/scancell-reports-progress-across-a-number-of-trials/21194198.html" rel="nofollow - http://www.sharecast.com/news/scancell-reports-progress-across-a-number-of-trials/21194198.html


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Nov 22 2013 at 11:48am
Immune system mutations found in breast cancers

http://www.medicalnewstoday.com/releases/269047.php" rel="nofollow - http://www.medicalnewstoday.com/releases/269047.php


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Mar 07 2014 at 9:07am
Some cancers evade detection by silencing parts of immune system cells
http://www.medicalnewstoday.com/releases/273535.php?tw" rel="nofollow - http://www.medicalnewstoday.com/releases/273535.php?tw


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: May 26 2014 at 11:35pm
Research Worth Watching: Immunotherapy
http://blog.dslrf.org/?p=1996" rel="nofollow - http://blog.dslrf.org/?p=1996


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jun 03 2014 at 10:41pm
Immunotherapy May Be an Option in Challenging Breast Cancer, Mayo Clinic Study Finds

 A promising new study from Mayo Clinic, in conjunction with Caris Life Sciences, points to immunotherapy as a possible treatment option for patients with the difficult-to-treat triple negative breast cancer mutation. The study was presented this week at the 50th annual meeting of the American Society of Clinical Oncology in Chicago.

“This study may change our ability to treat triple negative breast cancer patients,” says Barbara Pockaj, M.D., lead investigator of the study and Mayo Clinic surgeon. “We may have signs that these patients can be treated with immunotherapy. We don’t have a lot of options for these patients and this would really expand our options.”

Triple negative breast cancer is an aggressive form of breast cancer that evades the immune system because it lacks expression of genes for estrogen receptor, progesterone receptor and HER2. This limits treatment options. The study examined biomarkers involved in immune evasion including the gene PD-L1 and its association with other biological pathways as potential treatment options. In other cancers, patients who have the PD-L1 gene have been treated with immunotherapy – enhancing the body’s immune system – and some of the results have been dramatic, Dr. Pockaj says.

“This is important because immunotherapy is evolving as an effective treatment for patients with cancer,” she says. “We’ve seen remarkable results with patients with melanoma, renal cell carcinoma and even lung cancer. The question is, ‘Can we expand this type of treatment to patients with breast cancer?’”

The study analyzed 511 triple negative breast cancer samples using a multiplatform approach, including whole genome mRNA expression, protein expression, gene copy number changes and gene sequencing. The study found that 25 to 30 percent had the PD-L1 gene, which means those patients may be candidates for immunotherapy. There is a suggestion that the percentage may be even higher for patients who carry the BRCA1 gene, which produces tumor suppressor proteins. While the results need further investigation, they illustrate how molecular profiling can be used to identify potential treatment targets in triple negative breast cancer and other difficult-to-treat cancers.

“We now want to do validation studies in which we would hope to determine whether those patients who overexpress PD-L1 also have changes in their DNA repair genes,” Dr. Pockaj says. “And if they have both, it suggests the combination immunotherapy and chemotherapy may work.”

http://www.newswise.com/articles/immunotherapy-may-be-an-option-in-challenging-breast-cancer-mayo-clinic-study-finds" rel="nofollow - http://www.newswise.com/articles/immunotherapy-may-be-an-option-in-challenging-breast-cancer-mayo-clinic-study-finds


http://truebluetribune.com/caris-life-sciences-biomarker-research-suggests-role-for-immune-targeted-therapies-in-subsets-of-patients-with-triple-negative-breast-cancer-tnbc/3134" rel="nofollow - http://truebluetribune.com/caris-life-sciences-biomarker-research-suggests-role-for-immune-targeted-therapies-in-subsets-of-patients-with-triple-negative-breast-cancer-tnbc/3134



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: MomMom44
Date Posted: Jun 04 2014 at 5:27pm
This looks so promising!  Thank you for making us aware of it Donna.  Wonder how far off this is?

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DX TNBC 1/14; age 66; Stage 1; Grade 2; 1.2 cm; 0/2 nodes; lumpectomy; BRAC Neg; 4 DD AC; Completed 12 weekly Taxol July 2014; Radiation August 2014


Posted By: Mark4Lori
Date Posted: Jun 11 2014 at 1:02pm
I agree.  This looks great! 


Posted By: 123Donna
Date Posted: Sep 04 2014 at 11:28pm
This is a Phase 1 Clinical Trial:

Bristol-Myers Squibb and Celgene Enter Clinical Collaboration Agreement to Evaluate Immunotherapy and Chemotherapy Combination Regimen

Phase I study to evaluate OPDIVO (nivolumab), Bristol-Myers Squibb’s investigational PD-1 immune checkpoint inhibitor, with Celgene’s ABRAXANE® for multiple cancers

http://news.bms.com/press-release/rd-news/bristol-myers-squibb-and-celgene-enter-clinical-collaboration-agreement-evalua" rel="nofollow - http://news.bms.com/press-release/rd-news/bristol-myers-squibb-and-celgene-enter-clinical-collaboration-agreement-evalua




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Oct 16 2014 at 11:38pm
Early clinical results with the drug, known as MPDL3280A, in so-called triple negative breast cancer will be revealed at the Dec. 9-13 San Antonio Breast Cancer Symposium.

Read more:  http://www.businessinsider.com/r-roche-extends-immunotherapy-fight-to-breast-cancer-2014-10#ixzz3GMzySTew" rel="nofollow - http://www.businessinsider.com/r-roche-extends-immunotherapy-fight-to-breast-cancer-2014-10#ixzz3GMzySTew


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Oct 18 2014 at 12:47pm
Merck and Roche are hoping to widen this novel approach to treat advanced triple negative breast cancer, which is notoriously impervious to some of the most effective therapies available for breast cancer, like hormone therapy and drugs that target HER2 receptors. The New Jersey-based drugmaker and Swiss company will present early clinical results at the San Antonio Breast Cancer Symposium in December, according to Reuters.

Roche's drug, MPDL3280A, has already posted encouraging results in bladder, lung and skin cancers though it's not yet approved to treat any indications. Meanwhile, Merck is studying how triple negative breast cancer patients fair with its PD-1 drug Keyruda, which won approval for melanoma and has shown promise in stomach and other cancers.

Bristol-Myers is also moving in on this target, with its August announcement that it will begin a Phase I breast cancer trial of its PD-1 drug nivolumab alongside Celgene ( http://www.fiercebiotech.com/tags/celgene" rel="nofollow - $CELG ) Abraxane.

http://www.fiercebiotech.com/story/merck-and-roche-prep-breast-cancer-data-promising-pd-1-drugs/2014-10-17" rel="nofollow - http://www.fiercebiotech.com/story/merck-and-roche-prep-breast-cancer-data-promising-pd-1-drugs/2014-10-17



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: kellly
Date Posted: Oct 18 2014 at 3:26pm
Thanks for sharing Donna! 
 Do you have any information on the trial?



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DX '08,34yr, TN-IBC, gr3, 4 FEC, 3 Taxotere, biMST ->3/9 nodes+, 23rad's, BRCA-, bi DIEP '09. '12 son born!
Dx2 feb'14 mets subcl. & mediast. lymph nodes.CHEK2-. Olaparib, Carboplatin. Now: Nivolumab


Posted By: 123Donna
Date Posted: Oct 18 2014 at 5:12pm
Clinical Trials with PD-1 and breast cancer

http://clinicaltrials.gov/ct2/results?term=PD-1+and+triple+negative+breast+cancer&recr=Open&no_unk=Y" rel="nofollow - http://clinicaltrials.gov/ct2/results?term=PD-1+and+triple+negative+breast+cancer&recr=Open&no_unk=Y

http://clinicaltrials.gov/ct2/results?term=PD-1+and+breast+cancer&recr=Open&no_unk=Y" rel="nofollow - http://clinicaltrials.gov/ct2/results?term=PD-1+and+breast+cancer&recr=Open&no_unk=Y


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Oct 23 2014 at 9:36pm
Keytruda, has already been approved by the FDA for treating advanced melanoma. However, the drug showed promise in treating other cancers including triple-negative breast cancer (TNBC). TNBC is difficult to cure because it does not usually improve after using traditionally effective treatments such as hormone therapy. Merck hopes to change that with Keytruda.

The drug works by inhibiting a protein called programmed death receptor 1 (PD-1), which negatively regulates immune response. Tumors use PD-1 to avoid cells that fight against diseases. PD-1 blockers are a new class of immunotherapy drugs.

  http://www.financialbuzz.com/merck-co-nyse-mrk-set-to-announce-breast-cancer-drug-results-in-december-market-news-166552" rel="nofollow - http://www.financialbuzz.com/merck-co-nyse-mrk-set-to-announce-breast-cancer-drug-results-in-december-market-news-166552

Keytruda will reportedly be the sixth most expensive drug on the market at a price of $12,500 per patient per month.



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Nov 12 2014 at 8:50pm
Caris Life Sciences Study Shows Molecular Profiling May Expand Use of PD-1 and PD-L1 Inhibitors to Wide Variety of CancersResults Published in Cancer Epidemiology Biomarkers & Prevention Demonstrate Utility of Caris Molecular Intelligence™ in Exploring Expression of Targetable Immune Proteins

More:  http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=103630#.VGQKT_nF98E#ixzz3IuR7fS96" rel="nofollow - http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=103630#.VGQKT_nF98E#ixzz3IuR7fS96


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Dec 11 2014 at 8:07am
PD-L1 and MEK inhibition may be synergistic in triple-negative breast cancer
MHC-I/II and PD-L1 expression appeared to have opposing effects on the immune system in patients with triple-negative breast cancer who had residual disease after neoadjuvant chemotherapy, according to study results presented at the  http://www.healio.com/hematology-oncology/cb/%7Beb123f63-624f-438d-980f-dd7e89fed06f%7D/highlights-from-sabcs-2014" rel="nofollow - San Antonio Breast Cancer Symposium .

These findings suggest that combined PD-L1 and MEK inhibition may have a synergistic antitumor effect in triple-negative breast cancer, researchers said.

“Increased tumor-infiltrating lymphocytes have been shown to predict favorable patient prognosis in triple-negative and  http://www.healio.com/hematology-oncology/breast-cancer/news/online/%7B7ee3b8ce-a846-4a22-952f-f37fca39f7f5%7D/pertuzumab-conferred-unprecedented-os-benefit-in-her-2positive-metastatic-breast-cancer" rel="nofollow - HER-2–positive breast cancers  in a variety of different disease states, including in the adjuvant setting,” Justin M. Balko, PharmD, PhD, assistant professor of medicine and cancer biology at Vanderbilt University in Nashville, Tenn., said during a presentation. “Increased tumor-infiltrating lymphocytes in pretreatment biopsies can also predict pathological complete response in the neoadjuvant setting, and in patients who lack a pathological complete response to neoadjuvant chemotherapy, increased tumor infiltrating lymphocytes in residual disease can predict improved RFS and OS.”

To read more:

http://www.healio.com/hematology-oncology/breast-cancer/news/online/%7Bf3d801cf-3605-40b6-a68f-775c712c7bc3%7D/pd-l1-and-mek-inhibition-may-be-synergistic-in-triple-negative-breast-cancer" rel="nofollow - http://www.healio.com/hematology-oncology/breast-cancer/news/online/%7Bf3d801cf-3605-40b6-a68f-775c712c7bc3%7D/pd-l1-and-mek-inhibition-may-be-synergistic-in-triple-negative-breast-cancer



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: CatWhispurrer
Date Posted: Dec 11 2014 at 2:47pm
Thanks Donna.   Such exciting news.   I am in a different clinical trial for stage IV TNBC at Vanderbilt and so far, I have had complete response.    I am excited to see other alternatives being developed, especially less toxic ones!Thumbs Up


-------------
Found lump 9/16/11, age 55, Diagnosed 10/27 IDC TN, LX/SNB 12/7/11, Stage 1, Grade 3, 1.8 cm, 0/3 nodes, BRCA-, DD A/C on 1/23/12, followed by DD Taxol. 3/14/14 Stage IV, 3/26/14 Paclitaxel


Posted By: katrinaS
Date Posted: Dec 11 2014 at 8:13pm
Catwhispurrer,
What clinical trial are you in?  I have been in Roche/Genentech's MPDL3280A clinical trial for anti-PDL1 treatment and had a lot of progression on it and was taken off the trial.  Thank you,
Katrina


Posted By: 123Donna
Date Posted: Dec 11 2014 at 8:24pm
Early trial of new drug shows promise for patients with triple-negative breast cancer
In patients with metastatic triple-negative breast cancer—a disease with no approved targeted therapies—infusion of pembrolizumab produced durable responses in almost one out of five patients enrolled in a phase-Ib clinical trial, according to data presented Dec. 10, at the 2014 San Antonio Breast Cancer Symposium.

The multi-center, non-randomized trial was designed to evaluate the safety, tolerability and  http://medicalxpress.com/tags/antitumor+activity/" rel="nofollow - antitumor activity  of bi-weekly infusions of pembrolizumab (MK-3475, marketed as Keytruda®). The researchers enrolled 27 http://medicalxpress.com/tags/patients/" rel="nofollow - patients , aged 29 to 72 years, who had metastatic  http://medicalxpress.com/tags/triple-negative+breast+cancer/" rel="nofollow - triple-negative breast cancer  that either relapsed after treatment for early stage disease or progressed on therapy for advanced disease.

"For this group of patients our  http://medicalxpress.com/tags/treatment+options/" rel="nofollow - treatment options  are limited to chemotherapy," said study director Rita Nanda, MD, assistant professor of medicine and associate director of the breast medical oncology program at the University of Chicago.

All patients in the study had triple-negative tumors with high levels of a protein called programmed death-ligand 1 (PD-L1). This protein can suppress the immune system's efforts to eliminate  http://medicalxpress.com/tags/cancer+cells/" rel="nofollow - cancer cells . Pembrolizumab is a monoclonal antibody designed to help reactivate a person's own immune system to help fight the tumor.

"Pembrolizumab appears to make a significant difference for a subset of patients," Nanda said. "Of the 27 patients in this study with measurable disease, five (18.5%) had encouraging results. One patient had a complete response, and four had a partial response to treatment."

Responses for those five patients were long-lasting. Meanwhile, the patient with a complete response and two of those with a partial response continue to be treated with pembrolizumab.

An additional seven patients had stable disease, and twelve had progressive disease. Three patients left the trial early because their disease progressed.

Pembrolizumab, approved in September 2014 by the Food and Drug Administration for treatment of melanoma, does have some side effects. But Nanda said those are generally mild and easy to manage. They include fatigue, cough, nausea, itchy skin, rash, decreased appetite, constipation, joint pain and diarrhea.

In this trial, four of the 27 patients experienced at least one severe or life-threatening drug-related adverse event. One patient died while on the study treatment.

"The median survival for patients with triple-negative breast cancer is approximately one year," Nanda said. "We need better treatments for this disease. The promising activity of pembrolizumab seen in PD-L1-expressing, triple-negative  http://medicalxpress.com/tags/breast+cancer/" rel="nofollow - breast cancer  is exciting, and certainly worthy of further investigation."

An important next step, she said, is to learn how to predict which patients are most likely to benefit and how to manage the drug's toxicity.

http://medicalxpress.com/news/2014-12-early-trial-drug-patients-triple-negative.html" rel="nofollow - http://medicalxpress.com/news/2014-12-early-trial-drug-patients-triple-negative.html



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Dec 12 2014 at 10:58pm
Results of the first phase I trials of programmed cell death 1 (PD-1) and PD-L1 inhibitors in breast cancer were presented at the 2014 San Antonio Breast Cancer Symposium (SABCS), held December 9–13 in San Antonio, Texas. - See more at: http://www.cancernetwork.com/sabcs-2014/immunotherapy-yields-response-triple-negative-breast-cancer#sthash.ecVKpD4V.dpuf

A phase II trial of pembrolizumab in patients with advanced triple-negative breast cancer is expected to start in the first half of 2015. - See more at: http://www.cancernetwork.com/sabcs-2014/immunotherapy-yields-response-triple-negative-breast-cancer#sthash.ecVKpD4V.dpuf

http://www.cancernetwork.com/sabcs-2014/immunotherapy-yields-response-triple-negative-breast-cancer" rel="nofollow - http://www.cancernetwork.com/sabcs-2014/immunotherapy-yields-response-triple-negative-breast-cancer


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: kellly
Date Posted: Dec 14 2014 at 8:11am
https://clinicaltrials.gov/ct2/results?term=pdl1+breast+cancer&Search=Search

two trials, both anti PDL1, but 2 different drugs.
so there are several anti pdl-1 drugs. what could be the difference between them? Donna do you know how that works?


-------------
DX '08,34yr, TN-IBC, gr3, 4 FEC, 3 Taxotere, biMST ->3/9 nodes+, 23rad's, BRCA-, bi DIEP '09. '12 son born!
Dx2 feb'14 mets subcl. & mediast. lymph nodes.CHEK2-. Olaparib, Carboplatin. Now: Nivolumab


Posted By: CatWhispurrer
Date Posted: Dec 14 2014 at 10:23pm
Katrina - I am in a trial with Cisplatin and GDC-019 (Pi3K inhibitor) at Vanderbilt.


-------------
Found lump 9/16/11, age 55, Diagnosed 10/27 IDC TN, LX/SNB 12/7/11, Stage 1, Grade 3, 1.8 cm, 0/3 nodes, BRCA-, DD A/C on 1/23/12, followed by DD Taxol. 3/14/14 Stage IV, 3/26/14 Paclitaxel


Posted By: 123Donna
Date Posted: Dec 16 2014 at 8:27am
Pembrolizumab (MK-3475 - Keytruda)

In patients with metastatic triple-negative breast cancer--a disease with no approved targeted therapies--infusion of pembrolizumab produced durable responses in almost one out of five patients enrolled in a phase-Ib clinical trial, according to data presented at the 2014 San Antonio Breast Cancer Symposium.

The multi-center, non-randomized trial was designed to evaluate the safety, tolerability and antitumor activity of bi-weekly infusions of pembrolizumab (MK-3475, marketed as Keytruda®). The researchers enrolled 27 patients, aged 29 to 72 years, who had metastatic triple-negative  http://www.medicalnewstoday.com/articles/37136.php" rel="nofollow - breast cancer  that either relapsed after treatment for early stage disease or progressed on therapy for advanced disease.

http://www.medicalnewstoday.com/releases/286848.php?tw" rel="nofollow - http://www.medicalnewstoday.com/releases/286848.php?tw



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: positive_attitude
Date Posted: Dec 18 2014 at 9:21pm
Is anyone familiar with CAR T-cell immune-therapy? It seems to be very successful for some other deadly cancers http://www.cancer.gov/cancertopics/research-updates/2013/CAR-T-Cells" rel="nofollow - : http://www.cancer.gov/cancertopics/research-updates/2013/CAR-T-Cells . Someone said, "[The CAR T cells are] much more potent than anything we can achieve [with other immune-based treatments being studied]."

I also came across a trial of CAR-T for breast cancer. TNBC and metastatic BC can participate. Even newly diagnosed TNBC. Is anyone on this trial: http://clinicaltrials.gov/ct2/show/NCT01837602" rel="nofollow - https://clinicaltrials.gov/ct2/show/NCT01837602 ?

Rebecca




-------------
DX IDC TNBC May, 2014, 4.7cm, 5.8cm on Taxol. Taxol 4 weeks, AC 6. double mastectomy OCT 2014. 1.8cm residual in breast and 3mm a lymph node. BRCA-. 11/17 Abraxane,5FU.11/20, rads, 1/19 FUMEPx2


Posted By: 123Donna
Date Posted: Jan 12 2015 at 8:13pm

OncoSec Medical Plans to Initiate Pilot Study in Triple Negative Breast Cancer

Study to Be Conducted at Stanford University

OncoSec Medical Inc. (OTCQB:  http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Ffinance.yahoo.com%2Fq%3Fs%3Doncs&esheet=51016994&newsitemid=20150112005249&lan=en-US&anchor=ONCS&index=1&md5=7ed4e34e75653a683b1b7c305eee7563" rel="nofollow - ONCS ), a company developing DNA-based intratumoral cancer immunotherapies, plans to initiate a pilot study to assess IL-12 ImmunoPulse in patients with Triple Negative Breast Cancer (TNBC). The study will be conducted at Stanford University with Melinda L. Telli, MD, serving as lead investigator.

This pilot study is designed to assess whether IL-12 ImmunoPulse increases TNBC tumor immunogenicity by driving a pro-inflammatory cascade of events that leads to increases in cytotoxic tumor-infiltrating lymphocytes (TILs). The presence and number of TILs is thought to be a key requirement for promoting the anti-tumor activity of antibodies like anti-PD-1/PD-L1. By driving cytotoxic immune cells into the tumor, IL-12 ImmunoPulse may be an ideal candidate to combine with checkpoint blockade therapies which reported some activity in TNBC.

Worldwide, TNBC amounts to approximately 200,000 cases each year and accounts for approximately 20 percent of all breast cancer. It is most commonly diagnosed in younger women (less than 40 years) and is characterized by higher relapse rates when compared with estrogen receptor (ER)-positive breast cancers. TNBC is also associated with an increased risk of recurrence, both locally and in distant sites, including the lung and brain. Advanced TNBC remains a significant area of unmet medical need and there is no established standard-of-care. Treatment generally includes chemotherapy, with or without radiation and/or surgery. However, no treatment regimen has clearly demonstrated superiority.

Previous studies have reported that patients with TNBC tumors associated with markers of inflammation, such as the presence of tumor-infiltrating lymphocytes (TILs), have improved survival, and recent data presented have shown that TNBC is responsive to immunotherapies like anti-PD-1 or anti-PD-L1 checkpoint blockade drugs. Response rates in TNBC patients receiving either anti-PD-1 or anti-PD-L1 in early Phase 1 studies were reported to be 18 to 33 percent.

“The data presented at the 2014 San Antonio Breast Cancer Symposium (SABCS), combined with historical data correlating increased immunogenicity with improved survival in TNBC, strongly suggest that treatments aimed at augmenting pro-inflammatory signals within the tumor have a central role in improving the clinical outcomes for TNBC patients,” said Mai H. Le, Chief Medical Officer at OncoSec Inc. “We are very excited to be working closely with our colleagues at Stanford on this pilot clinical program, which is specifically designed to evaluate the role of IL-12 ImmunoPulse in promoting tumor immunogenicity in TNBC and, ultimately, improving patient outcomes.”

Dr. Robert H. Pierce, OncoSec’s Chief Scientific Officer, commented: “Both the Merck and Roche/Genentech studies presented at SABCS indicate that a distinct sub-population of TNBC patients respond to inhibition of the immunosuppressive PD-1/PD-L1 axis. Both independent studies support the emerging paradigm that the presence of ‘stalled’ CD8 T cells (so called ‘adaptive resistance’) drives the response to PD-1/PD-L1 therapeutics. We are excited that two experts in this field, Drs. Holbrook Kohrt (Stanford) and Paul Tumeh (UCLA), will be involved in analyzing our samples from this pilot study.”

http://www.businesswire.com/news/home/20150112005249/en/OncoSec-Medical-Plans-Initiate-Pilot-Study-Triple#.VLRxOSvF98E" rel="nofollow - http://www.businesswire.com/news/home/20150112005249/en/OncoSec-Medical-Plans-Initiate-Pilot-Study-Triple#.VLRxOSvF98E




-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: tripleneg-mom
Date Posted: Jan 25 2015 at 3:39pm
What a great thread with excellent information on immunotherapy.  I'm trying to get on an immunotherapy trial at MD Anderson but so far no luck.  It sounds so promising.  

I ran across the following article.  It's focused alot on melenoma but I found it interesting that some of these patient stories mention how it took awhile to actually see good results.

http://www.wsj.com/articles/cancers-super-survivors-how-immunotherapy-is-transforming-oncology-1417714379?mod=trending_now_2" rel="nofollow - http://www.wsj.com/articles/cancers-super-survivors-how-immunotherapy-is-transforming-oncology-1417714379?mod=trending_now_2



Posted By: Lillie
Date Posted: Jan 25 2015 at 6:03pm
WOW!!
I watched the video of each person and have a feeling that the immunotherapy trial is a winner for melanoma.
The comment at the end from the man whose wife has stage 4 triple negative breast cancer really caught my eye. Wouldn't it be wonderful if it WORKS for us as well as for melanoma.

God Bless,
Lillie

-------------
Dx 6/06 age 65,IDC-TNBC
Stage IIb,Gr3,2cm,BRCA-
6/06 L/Mast/w/SNB,1of3 Nodes+
6/06 Axl. 9 nodes-
8/8 thru 11/15 Chemo (Clin-Trial) DD A/Cx4 -- DD taxol+gemzar x4
No Rads.
No RECON - 11/2018-12 yrs NED


Posted By: Lillie
Date Posted: Jan 26 2015 at 7:45pm
Double WOW!
Guess what the topic of conversation was today at lunchtime. Melanoma, stage iv triple negative breast cancer and YERVOY.
A drug representative provided lunch for the doctors and staff. As I said the topic of conversation was YERVOY and a stage iv TN cancer patient. The oncologist and staff are hoping to get her insurance to give the go ahead with the Yervoy. I'm praying for NED for the lady who hopefully will be getting YERVOY.

God Bless,
Lillie

-------------
Dx 6/06 age 65,IDC-TNBC
Stage IIb,Gr3,2cm,BRCA-
6/06 L/Mast/w/SNB,1of3 Nodes+
6/06 Axl. 9 nodes-
8/8 thru 11/15 Chemo (Clin-Trial) DD A/Cx4 -- DD taxol+gemzar x4
No Rads.
No RECON - 11/2018-12 yrs NED


Posted By: 123Donna
Date Posted: Jan 26 2015 at 8:20pm
Lillie,

Thanks so much for sharing!  Yervoy's clinical name is ipilimumab.  Hope it proves useful as a targeted therapy for TNBC.  

http://www.medscape.com/viewarticle/803014_13" rel="nofollow - http://www.medscape.com/viewarticle/803014_13

The first immune-checkpoint inhibitor to be tested in a clinical trial was ipilimumab (Yervoy, Bristol-Myers Squibb), an anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) mAb. CTLA-4 belongs to the immunoglobulin superfamily of receptors, which also includes programmed cell death protein 1 (PD-1), B and T lymphocyte attenuator, T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), and V-domain immunoglobulin suppressor of T cell activation. In 2011, the US Food and Drug Administration approved the use of ipilimumab in patients with metastatic melanoma, either as initial therapy or after relapse.


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: tripleneg-mom
Date Posted: Jan 29 2015 at 4:50pm
Wow Lillie, that's amazing.  I wonder what is behind the decision to try to get the lady Yervoy vs the Nivolumab (its the anti PD-1), also by Bristol-Meyers.  There's a study that is actually trying these 2 together, and includes TNBC in the criteria.  MD Anderson (where I go) is one of the locations, but the magic gatekeeper has those gates closed for some reason.

http://clinicaltrials.gov/ct2/show/NCT01928394?term=NCT01928394&rank=1" rel="nofollow - https://clinicaltrials.gov/ct2/show/NCT01928394?term=NCT01928394&rank=1   


Posted By: 123Donna
Date Posted: Mar 01 2015 at 11:28am
In Pre-Clinical Studies Ibrutinib Enhances Anti-tumor Activity When Combined With An Anti-PD-L1 Antibody

http://www.pipelinereview.com/index.php/2015022857047/Small-Molecules/In-Pre-Clinical-Studies-Ibrutinib-Enhances-Anti-tumor-Activity-When-Combined-With-An-Anti-PD-L1-Antibody.html" rel="nofollow - http://www.pipelinereview.com/index.php/2015022857047/Small-Molecules/In-Pre-Clinical-Studies-Ibrutinib-Enhances-Anti-tumor-Activity-When-Combined-With-An-Anti-PD-L1-Antibody.html


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Mar 01 2015 at 1:52pm

New test predicts a woman's chance of surviving breast cancer: Images track hotspots in tumours where the immune system attacks disease cells


  • Test tracks how strongly the immune system is working to control tumours
  • Location of immune cell clusters is 'as important as the number of cells'  
  • Test analyses images, checking cells are well-placed to attack cancer
  • Those at low risk survived 50 per cent longer before the cancer spread 


Read more:  http://www.dailymail.co.uk/health/article-2972285/New-test-predicts-woman-s-chance-surviving-breast-cancer-Images-track-disease-hotspots-body-reveal-progression.html#ixzz3TA501EmY" rel="nofollow - http://www.dailymail.co.uk/health/article-2972285/New-test-predicts-woman-s-chance-surviving-breast-cancer-Images-track-disease-hotspots-body-reveal-progression.html#ixzz3TA501EmY  

http://www.eurekalert.org/pub_releases/2015-02/iocr-nbc022715.php" rel="nofollow - http://www.eurekalert.org/pub_releases/2015-02/iocr-nbc022715.php



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Mar 10 2015 at 8:18am
http://money.cnn.com/news/newsfeeds/articles/prnewswire/LN51278.htm" rel="nofollow - http://money.cnn.com/news/newsfeeds/articles/prnewswire/LN51278.htm

-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Apr 16 2015 at 1:24pm

Roche to Skip Ahead to Late-Stage Study for Breast Cancer Drug

Roche Holding AG will skip a mid-stage study of an experimental immunotherapy for breast cancer and proceed directly to a phase 3 trial later this year. 

The Swiss company will study MPDL3280A for triple-negative breast cancer, which is currently treated mostly with chemotherapy, spokeswoman Holli Dickson said in a phone interview. The drug will be tested in combination with chemotherapy.

http://www.swissinfo.ch/eng/roche-to-skip-ahead-to-late-stage-study-for-breast-cancer-drug/41384180" rel="nofollow - http://www.swissinfo.ch/eng/roche-to-skip-ahead-to-late-stage-study-for-breast-cancer-drug/41384180




-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: kellly
Date Posted: Apr 17 2015 at 8:23am
very promising.

-------------
DX '08,34yr, TN-IBC, gr3, 4 FEC, 3 Taxotere, biMST ->3/9 nodes+, 23rad's, BRCA-, bi DIEP '09. '12 son born!
Dx2 feb'14 mets subcl. & mediast. lymph nodes.CHEK2-. Olaparib, Carboplatin. Now: Nivolumab


Posted By: 123Donna
Date Posted: Apr 20 2015 at 11:19pm
http://www.medscape.com/viewarticle/843418" rel="nofollow - http://www.medscape.com/viewarticle/843418

-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: May 27 2015 at 8:26am
Immunotherapy Lies on the Horizon for Breast Cancer

http://www.clinicaloncology.com/ViewArticle.aspx?d=Solid+Tumors&d_id=148&i=May+2015&i_id=1191&a_id=32498" rel="nofollow - http://www.clinicaloncology.com/ViewArticle.aspx?d=Solid+Tumors&d_id=148&i=May+2015&i_id=1191&a_id=32498


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: kellly
Date Posted: May 28 2015 at 5:27am
very exciting !
Thanx for posting Donna,
i am trying to get in a trial checkpoint inhibitor trial, but havent been succesful yet. 


-------------
DX '08,34yr, TN-IBC, gr3, 4 FEC, 3 Taxotere, biMST ->3/9 nodes+, 23rad's, BRCA-, bi DIEP '09. '12 son born!
Dx2 feb'14 mets subcl. & mediast. lymph nodes.CHEK2-. Olaparib, Carboplatin. Now: Nivolumab


Posted By: 123Donna
Date Posted: May 30 2015 at 2:48pm
TESARO and Merck to Collaborate on a Combination Study of Niraparib and KEYTRUDA(R) (Pembrolizumab)

Clinical Trial Will Evaluate TESARO's PARP Inhibitor With Merck's anti-PD-1 Therapy in Patients With Breast and Ovarian Cancers

To evaluate the combination of TESARO's niraparib plus Merck's anti-PD1 therapy, KEYTRUDA® (pembrolizumab), in a Phase 1/2 clinical trial.

This trial is planned to evaluate the preliminary safety and efficacy of niraparib plus KEYTRUDA in patients with triple negative breast cancer or ovarian cancer. This trial will be conducted by TESARO and Merck, through a subsidiary, and is expected to begin by the end of 2015.

"The combination of a PARP inhibitor and anti-PD-1 antibody in this study has the potential to build upon the responses already observed with each of these compounds as monotherapies," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "Treatment options for patients with triple negative breast cancer are extremely limited, and we look forward to assessing this exciting new approach."

http://globenewswire.com/news-release/2015/05/30/740632/10136643/en/TESARO-and-Merck-to-Collaborate-on-a-Combination-Study-of-Niraparib-and-KEYTRUDA-R-Pembrolizumab.html" rel="nofollow - http://globenewswire.com/news-release/2015/05/30/740632/10136643/en/TESARO-and-Merck-to-Collaborate-on-a-Combination-Study-of-Niraparib-and-KEYTRUDA-R-Pembrolizumab.html


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: May 31 2015 at 12:07pm
Genentech's PD-L1 breakthrough star 'atezo' positioned to vault ahead on cancer
MPDL3280A--it's atezolizumab now, or just "atezo" 

"Behind the headline presentations here at ASCO, you'll find one of the biggest players in immuno-oncology quietly positioning itself to vault into a leading role in the fast-emerging market, using its in-house technology to best identify the patients most likely to respond to their checkpoint inhibitor and then rapidly exploiting that edge with a full slate of combination therapies matched to their lead program. 


http://www.fiercebiotech.com/tags/genentech" rel="nofollow - Genentech  arrived at  http://www.fiercebiotech.com/tags/asco-2015" rel="nofollow - ASCO  with a new name for MPDL3280A--it's atezolizumab now, or just "atezo" for shorthand--which is in 10 Phase III studies (an 11th is being readied) amid a blizzard of 36 clinical trials. An abstract to be posted here at ASCO points to newly identified subpopulations of  http://www.fiercebiotech.com/tags/lung-cancer" rel="nofollow - lung cancer  patients who may turn out to be ideally suited to atezo, which has "breakthrough" status at the FDA as regulators appear eager to approve these new drugs.


There's also an intriguing experimental treatment now in Phase I--the "anti-CEA" RG7802 program--that promises to add a brand new  http://www.fiercebiotech.com/tags/t-cells-1" rel="nofollow - T cell  approach to fighting cancer that is being lined up for a combo approach with atezo. Investigators are using bispecific antibody technology to direct a T cell attack directly against the CEA antigen that clusters on the surface of cancer cells. And Dan Chen, Genentech's global development team leader for immuno-oncology, says using that in combination with atezo "makes total sense."

http://www.fiercepharma.com/offer/mwvhealthcare_june2015?source=drawer" rel="nofollow -
Susan Zager's insight:

According to Chen, "The bispecific antibody RG7802 treatment is "similar to but different from CAR-T," referring to the hot new field that reengineers T cells with a chimeric antigen receptor to direct an attack against cancer cells. In this case, Genentech has designed a bispecific antibody that attaches to cancer cells as well as T cells. T cells that would normally be circulating in search of an invader like the flu are redirected to attack cancer cells. In preclinical studies, he says, it has looked like one of the most potent cancer therapies he's seen. 

In Chen's view of the next few years, the development of their checkpoint inhibitors will move past chemotherapy combinations to new approaches that involve a big step up through the use of more innovative matchups, with pipeline agents coming in to amp up impact. Roche has also paired itself with  http://www.fiercebiotech.com/tags/immatics" rel="nofollow - immatics biotechnologies , a German biotech that's been working on new  http://www.fiercebiotech.com/tags/cancer-vaccine" rel="nofollow - cancer vaccines . And there's an anti-OX40 approach that stimulates the production of T cells.

http://www.scoop.it/t/breast-cancer-news" rel="nofollow - http://www.scoop.it/t/breast-cancer-news


http://www.fiercebiotech.com/story/genentechs-pd-l1-breakthrough-star-atezo-positioned-vault-ahead-cancer/2015-05-30" rel="nofollow - http://www.fiercebiotech.com/story/genentechs-pd-l1-breakthrough-star-atezo-positioned-vault-ahead-cancer/2015-05-30



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Sep 03 2015 at 7:31pm
The inhibition of CDK 4/6 and PD-1 represent two of the most exciting developments in the field of metastatic breast cancer. Following an accelerated approval in February 2015, the CDK4/6 inhibitor palbociclib (Ibrance) has continued to make headlines as an exciting new agent for patients with HR-positive metastatic breast cancer. Additionally, PD-1 and PD-L1 inhibitors have shown early signs of promise for patients with metastatic triple-negative breast cancer (TNBC).

The phase II PALOMA-1 trial,1 which was the basis for the approval of palbociclib, found that the novel CDK 4/6 inhibitor in combination with letrozole (Femara) reduced the risk of disease progression by 51% compared with letrozole alone. The median progression-free survival (PFS) with palbociclib was 20.2 versus 10.2 months for letrozole alone (HR, 0.488; P = .0004).

At the 2015 ASCO Annual Meeting, the PALOMA-3 trial found that palbociclib plus fulvestrant (Faslodex) improved PFS compared with fulvestrant alone in women with HR-positive, HER2-negative metastatic breast cancer following progression on prior endocrine therapy.2 At the time of the interim analysis, the median PFS was 9.2 months for palbociclib plus fulvestrant and 3.8 months for placebo plus fulvestrant (HR, 0.422; 95% CI, 0.318-0.560; P <.0001).

In addition to this now FDA-approved approach, two early phase clinical trials have shown potential for PD-1/PD-L1 inhibition in pretreated patients with TNBC. In the KEYNOTE-012 trial,3 pembrolizumab demonstrated an overall response rate (ORR) of 18.5%. In a similar patient population, the PD-L1 inhibitor atezolizumab showed an ORR of 19%.4 Larger trials are now looking to confirm these findings. - See more at:
http://www.onclive.com/web-exclusives/breast-cancer-pioneer-examines-novel-therapies-for-metastatic-breast-cancer" rel="nofollow - http://www.onclive.com/web-exclusives/breast-cancer-pioneer-examines-novel-therapies-for-metastatic-breast-cancer


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Sep 20 2015 at 8:52pm
http://www.mdanderson.org/publications/oncolog/previous-issues/2015-july/immunotherapy-trials-offer-hope-to-patients-with-high-risk-or-metastatic-breast-cancer.html" rel="nofollow - http://www.mdanderson.org/publications/oncolog/previous-issues/2015-july/immunotherapy-trials-offer-hope-to-patients-with-high-risk-or-metastatic-breast-cancer.html

Triage Program for Triple-Negative Breast Cancer

Triple-negative breast cancers—those that do not express estrogen receptors, progesterone receptors, or HER2—have about a 50% chance of responding to standard neoadjuvant chemotherapy. For patients whose cancer does not respond and who therefore are at higher risk for recurrence, researchers at MD Anderson Cancer Center have developed a triage program to find an appropriate experimental treatment.

At MD Anderson, patients with triple-negative breast cancer undergo genomic testing and then begin standard neoadjuvant chemotherapy. Dr. Litton said the triage program is similar in design to the I-SPY 2 TRIAL (see  http://www.mdanderson.org/publications/oncolog/previous-issues/2015-april/novel-trial-design-streamlines-development-of-breast-cancer-therapies.html" rel="nofollow - Novel Trial Design Streamlines Development of Breast Cancer Therapies , OncoLog, April 2015), except that patients begin treatment right away instead of waiting 2–3 weeks for the results of the genomic tests. When the results arrive, physicians also have clinical data that indicate whether the cancer is responding to standard chemotherapy.

“In the triage protocol, we can look at the early response and, for patients whose cancer is responding, we continue standard therapy and observe them; these patients will likely do well,” Dr. Litton said. “But we know that patients whose cancer does not respond to those initial doses of first-line treatment have only a 5% chance of a complete pathologic response to standard second-line treatment, and these patients are assigned to a clinical trial based on the results of the genomic tests. We’re in the process of opening a series of phase II trials of new treatments—including immunotherapy—for triple-negative breast cancer.”

Dr. Litton said that MD Anderson is the only institution in the United States to offer such a program for patients with triple-negative breast cancer.



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Sep 20 2015 at 8:54pm
Immunotherapy Trials Offer Hope to Patients with High-Risk or Metastatic Breast Cancer

Although the cure rate for breast cancer has risen steadily in recent decades, recurrent or metastatic disease remains difficult to control. To fight metastatic breast cancer and forestall the recurrence of high-risk primary disease, researchers at The University of Texas MD Anderson Cancer Center are using various techniques to boost the body’s immune system. Clinical trials of many of these therapies are already under way.

Graph

Patients with metastatic breast cancer treated with standard chemotherapy followed by the STn-KLH vaccine who also received endocrine therapy (tamoxifen) had a longer median overall survival than did those treated with standard chemotherapy followed by a control vector. Adapted from Ibrahim NK, et al. J Cancer 2013;4:577–584.

Recent research findings have sparked interest in the role of immunotherapy in breast cancer treatment, said Elizabeth Mittendorf, M.D., Ph.D., an associate professor in the Department of Surgical Oncology. “For a very long time, breast cancers were not thought to be immunogenic,” she said. “But data published in the past 2 years have shown that there are immune cells, including T cells, in breast tumors. This suggests that breast tumors are indeed immunogenic.”

Breakthroughs in immunotherapy against other types of cancer have encouraged research of its use against breast cancer. “The understanding of immunology in cancer is progressing very fast,” said Nuhad Ibrahim, M.D., a professor in the Department of Breast Medical Oncology. Citing the recent successes of immunotherapy drugs and vaccines in melanoma and prostate cancer, Dr. Ibrahim said, “In breast cancer we still have not had those kinds of breakthroughs, but there are definitely leads.”

Those leads have encouraged researchers to explore multiple avenues. “As much as we’ve always been fascinated with pushing the immune system, there has never been enough response to older immunotherapies, like interferon or interleukin-2, to benefit breast cancer patients,” said Debu Tripathy, M.D., a professor in and chair of the Department of Breast Medical Oncology. But with advances in therapeutic vaccines, immune checkpoint inhibitors, and other immunotherapies, he said, “We’ve finally crossed that threshold.”

Vaccines

Anti-MUC1 vaccines

“The early studies of immunotherapy with vaccines in patients with metastatic breast cancer did not meet their primary objective of improving overall survival, but we learned a lot from these studies,” said Dr. Ibrahim, who in the 1990s—along with James Murray III, M.D., a professor in the Department of Breast Medical Oncology—led a randomized trial of the sialyl-Tn–keyhole limpet hemocyanin (STn-KLH; also called Theratope) vaccine. The STn-KLH vaccine was derived from MUC1, a mucin expressed on the surface of a large proportion of breast cancer cells. The study did not meet its goal of extending progression-free survival for patients with metastatic breast cancer. However, in a post hoc analysis, the vaccine appeared to improve survival outcomes for patients who had previously been treated with tamoxifen.

Dr. Ibrahim, in collaboration with the U.S. National Cancer Institute, recently completed a trial of an anti-MUC1, anti–carcinoembryonic antigen vaccine combined with costimulatory molecules and given with docetaxel. The study’s report is under peer review.

OPT-822

OPT-822 is a carbohydrate vaccine similar in structure to the STn-KLH vaccine. Early studies of OPT-822 demonstrated prolonged overall survival in a subset of patients with metastatic breast cancer, especially when patients received low-dose cyclophosphamide. These findings led to a multicenter trial that recently completed enrollment. Dr. Murray is MD Anderson’s principal investigator for the trial, in which patients with metastatic breast cancer received low-dose cyclophosphamide with the OPT-822 vaccine along with the lipid adjuvant OPT-821 or placebo. The results are currently being analyzed.

E75

Of the breast cancer vaccines, the farthest along is E75 (nelipepimut-S, NeuVax), a peptide vaccine that is derived from human epidermal growth factor receptor 2 (HER2). Dr. Murray led a small phase I clinical trial of E75 combined with granulocyte-macrophage colony-stimulating factor (GMCSF) in patients with metastatic breast or ovarian cancer. Although HER2-specific immune responses were generated in most patients, no antitumor responses were observed, possibly because of the large tumor burden in the population studied.

“A general consensus at MD Anderson is that for vaccines to be successful against breast cancer, they need to be given in patients with low-volume disease, and that means giving them in the adjuvant therapy rather than the metastatic disease setting,” said Dr. Mittendorf, who also served as a principal investigator of early trials of the E75 vaccine.

Dr. Mittendorf is now the principal investigator of two multicenter trials of the E75 vaccine as adjuvant therapy for patients with HER2-positive breast cancer at high risk for recurrence: a phase III trial that has completed enrollment and a phase II trial of the vaccine plus trastuzumab that is currently enrolling patients.

GP2 and AE37

Two other HER2-derived peptide vaccines, GP2 and AE37, are under investigation as adjuvant therapy in an ongoing study that has completed enrollment. The GP2 vaccine—which resulted from research led by George Peoples Jr., M.D., an adjunct professor in the Department of Surgical Oncology—has greater immunogenicity than E75 and binds to both human leukocyte antigen (HLA)-A2 and HLA-A3. AE37 contains more than 10 amino acids, allowing for a broad range of immune stimulation in patients. AE37 was shown in preclinical studies to significantly enhance HER2-specific CD4-positive “helper” T cells.

Patients included in the ongoing adjuvant therapy study had a high risk for recurrence because of lymph node involvement or other factors such as high levels of HER2 expression; however, patients with HER2 immunohistochemistry scores indicating HER2-negative or borderline status were also included in the study. Because the two vaccines bind to different major histocompatibility complex class molecules, patients in the study were sorted according to their HLA status before randomization. Those who were positive for HLA-A2/A3 were randomly assigned to receive GM-CSF with or without GP2; those who were negative for HLA-A2/A3 were randomly assigned to receive GM-CSF with or without AE37.

Dr. Mittendorf presented the primary analyses of the study’s GP2 and AE37 arms in 2014 at the American Society of Clinical Oncology’s Breast Cancer Symposium and its Annual Meeting, respectively. “Both vaccines were safe and stimulated an immune response,” Dr. Mittendorf said. “AE37 had its strongest efficacy in patients with triple-negative breast cancer, and we’re developing a trial of the vaccine for these patients. GP2 had its strongest signal in HER2-positive patients who had received trastuzumab.”

E39 and J65

The E39 vaccine is derived from folate binding protein, which is expressed on the surface of most breast and ovarian cancer cells. Studies performed at MD Anderson demonstrated that E39 produced a robust immune response in ovarian cancer patients; however, whether this response would exhaust the immune system and prove counterproductive was not known. To determine the optimal strategy for using the vaccine, Dr. Mittendorf and her colleagues have begun a clinical trial at MD Anderson in which patients with breast or ovarian cancer receive E39 and J65, an attenuated version of E39, on various dosing schedules. Patients are randomly assigned to receive monthly injections according to one of three regimens: six injections of E39, three injections of E39 followed by three of J65, or three injections of J65 followed by three of E39.

“This trial will determine whether it’s better to come in hard with E39 for a few doses and then give J65 to soften the blow or start soft with J65 and ramp up slowly to E39,” Dr. Mittendorf said.

Immune checkpoint inhibitors

The relatively new class of drugs that inhibit immune checkpoints—cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and the PD-1 ligand (PD-L1)—has extended survival for patients with metastatic melanoma and has been found to be effective against several other types of cancer, including breast cancer.

Jennifer Litton, M.D., an associate professor in the Department of Breast Medical Oncology, has been an investigator on early trials of anti–PD-1 and anti–PD-L1 antibodies as well as two trials combining an anti–CTLA-4 antibody with an anti–PD-1 antibody in patients with metastatic breast cancer. “We didn’t see the huge numbers of responses we’ve seen with other breast cancer therapies, but the few patients who did respond had long-lasting responses,” Dr. Litton said. “In several national trials, we’ve had people with triple-negative breast cancer whose responses have lasted for years. That’s the game-changer.”

The responses to checkpoint inhibitors in patients with triple-negative breast cancer are particularly encouraging, Dr. Tripathy said, because these patients have limited treatment options. Triple-negative breast cancers tend to have more genetic mutations than do other breast cancer subtypes, and these mutations generate abnormal or overexpressed proteins that may present targets for immunotherapy. For example, a recent study by Drs. Mittendorf and Litton and their colleagues found that 20% of triple-negative breast cancers expressed PD-L1. “Triple-negative breast cancer may be a little more immunogenic than other subtypes,” Dr. Tripathy said, “and that may be an opportunity.”

Dr. Litton agreed. “Almost all of the checkpoint inhibitor trials we have in the planning stages are for patients with triple-negative breast cancer,” she said. Although most of these trials are for patients with metastatic disease, researchers are eager to learn whether checkpoint inhibitors can play a role in other settings.

Of particular interest is a clinical trial of the anti–PD-L1 antibody MPDL3280A with nanoparticle albumin-bound paclitaxel in patients with triple-negative breast cancer that did not respond to initial standard neoadjuvant treatment. Dr. Litton, the trial’s principal investigator, said the trial is part of a new MD Anderson program to identify patients whose cancer does not respond to standard chemotherapy and offer alternative treatments (see  http://www.mdanderson.org/publications/oncolog/previous-issues/2015-july/immunotherapy-trials-offer-hope-to-patients-with-high-risk-or-metastatic-breast-cancer.html#triage" rel="nofollow - Triage Program for Triple-Negative Breast Cancer , below).

Researchers are also planning a large trial of the anti–PD-1 antibody pembrolizumab as adjuvant therapy in patients with triple-negative breast cancer who have residual tumor cells in the breast or lymph nodes after neoadjuvant chemotherapy. “These patients have a higher risk of developing metastatic disease and dying of their disease later,” Dr. Tripathy said. Patients in the study will be randomly assigned to standard follow-up care with or without pembrolizumab.

In addition, a clinical trial of pembrolizumab will soon begin enrolling patients with inflammatory breast cancer, which is uncommon but aggressive. The trial, which aims to determine whether pembrolizumab can sustain the antitumor immune response started by standard-of-care chemotherapy, is led by Naoto Ueno, M.D., Ph.D., a professor in the Department of Breast Medical Oncology and executive director of the Morgan Welch Inflammatory Breast Cancer Program.

Although the survival effects of checkpoint inhibitors in breast cancer patients remain largely unknown, Dr. Litton is optimistic. “I think we’re only scratching the surface,” she said. “I think we’re going to see combinations of different immunotherapies as well as how to trigger an immune response in a greater percentage of breast cancer patients.”

Other immunotherapy approaches

“Our immunotherapy studies have moved from just vaccines to include checkpoint inhibitors and other immunotherapy strategies,” Dr. Mittendorf said. “And as an institution, we have the opportunity to do more.”

For example, Dr. Ibrahim is the principal investigator at MD Anderson for an ongoing multi-institutional trial of the oral immunostimulant indoximod with taxane-based chemotherapy for patients with HER2-negative metastatic breast cancer. Indoximod inhibits the indoleamine 2,3-dioxygenase pathway, which suppresses T cell activity.

Also under investigation are agents that block the action of interleukin-8 (CXCL8), which has an immunomodulatory effect and is associated with breast cancer growth and metastasis. A trial of one such agent, reparixin, which binds to the CXCL8 receptor CXCR1, is underway at MD Anderson and other institutions.

Preclinical studies of promising therapies also are underway. For example, Dr. Mittendorf said, Laurence Cooper, M.D., Ph.D., a professor in the Division of Pediatrics, is investigating the use of T cells modified with chimeric antigen receptors (see  http://www2.mdanderson.org/depts/oncolog/articles/14/5-may/5-14-2.html" rel="nofollow - “Sleeping Beauty” Technique Modifies T Cells to Treat B Cell Malignancies , OncoLog, May 2014) against triple-negative breast cancer.

Also on the horizon are studies of antiphosphatidylserine antibodies, which have been shown to improve the activity of taxanes against breast cancer. Likewise, studies are being planned of agents that stimulate the activity of natural killer cells and therefore may enhance the response to standard breast cancer drugs such as trastuzumab and toll-like receptor agonists.

Looking ahead

As researchers continue to elucidate the role of immunotherapy against breast cancer, clinical trials are increasingly becoming available for patients with metastatic disease and those with difficult-to-treat subtypes at high risk of recurrence. “There are trials that are open or in the process of opening for patients with triple-negative breast cancer,” Dr. Tripathy said. “The field is moving rapidly, and we hope that immunotherapy can prevent recurrences.”

For more information, contact Dr. Nuhad Ibrahim at 713-792-2817, Dr. Jennifer Litton at 713-792-2817, Dr. Elizabeth Mittendorf at 713-792-2362, Dr. James Murray at 713-792-2817, or Dr. Debu Tripathy at 713-792-2817. To learn more about ongoing clinical trials at MD Anderson for patients with breast cancer, visit http://www.clinicaltrials.org/" rel="nofollow - www.clinicaltrials.org .


http://www.mdanderson.org/publications/oncolog/previous-issues/2015-july/immunotherapy-trials-offer-hope-to-patients-with-high-risk-or-metastatic-breast-cancer.html" rel="nofollow - http://www.mdanderson.org/publications/oncolog/previous-issues/2015-july/immunotherapy-trials-offer-hope-to-patients-with-high-risk-or-metastatic-breast-cancer.html



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Oct 08 2015 at 11:14am
The drug, called Atezolizumab, is a form of immunotherapy, a new treatment option for patients with some types of lung cancer, bladder cancer and melanoma. Based on early data from a clinical trial, the treatment, which helps the immune system fight cancer, looks promising for women with metastatic, triple-negative  http://www.baltimoresun.com/health/health/breastcancer/" rel="nofollow - breast cancer .

To read the entire article about the research at John Hopkins:

http://www.baltimoresun.com/health/breastcancer/bs-hs-triple-negative-breast-cancer-drugs-20151007-story.html" rel="nofollow - http://www.baltimoresun.com/health/breastcancer/bs-hs-triple-negative-breast-cancer-drugs-20151007-story.html


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Oct 09 2015 at 8:55am
A Study of Atezolizumab (MPDL3280A) in Combination With Nab-Paclitaxel Compared With Placebo With Nab-Paclitaxel for Patients With Previously Untreated Metastatic Triple Negative Breast Cancer (IMpassion130)

http://clinicaltrials.gov/ct2/show/NCT02425891" rel="nofollow - http://clinicaltrials.gov/ct2/show/NCT02425891


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: mhurt84
Date Posted: Nov 06 2015 at 11:10am
Hi everyone,
Just checking in. Last time I posted a few things happened. Mom originally enrolled in a clinical trial using Taxol + Cobimetinib (MEK inhibitor) but had a solitary brain met diagnosed so she was taken off the trial (a few days without no active brain lesions was an inclusion criteria). Long story short she got SRS right away and instead a week later enrolled in this phase 3 trial you mentioned above of MPDL3280A/placebo +Abraxane.
 
End of the month will be her follow up scan to decide where we go from here..see how she is responding to therapy. Her oncologist is very aware that this is a randomized placebo controlled trial and he's blinded as to whether she is getting the immunotherapy. He plans to see the results of the 8 week follow up trial CT scan and go from there.
I was wondering if anyone else is on an immunotherapy? What are your side effects??
 
Mom is getting the typical side effects of Abraxane (mild neuropathy/fatigue/hair loss)
but she has itchy eyes/sandy eyes, not sure if that could be the immunotherapy.
 
This can be a bit nerve wrecking not knowing if she is actually getting the immunotherapy, also who knows if it would even work. There is a lot of promise but still under investigation...
 
Pembrolizumab (Keytruda) is the other immunotherapy opening up as monotherapy soon also for metastatic TNBC patients. My moms oncologist has mentioned this to me. He has this in mind if we come to find out that she could indeed be on placebo/not MPDL3280a and there is any sign of progression, he can unblind himself...
 
I know she is still getting standard of care with Abraxane and have read some ladies that this therapy has conrolled/brought them to NED.
 
Thats what I am praying for <3!!
 
Just wanted to see if others out there are on these immunotherapies (Nivolumab/Pembrolizumab/MPDL now called Azetolizumab)? share your experiences...
I dont see much post about it and would love to share her experience with others...
 
Thank you!!!
God bless you all <3


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Daughter-Mom w/ TNBC 9/15 mets to lungs and bones-Dx 2011 TNBC stage IIA s/p MX, Chemo (ACT), Radiation.
" Trust in the Lord with all your heart..acknowledge him..and he shall direct your paths"


Posted By: gordon15
Date Posted: Nov 06 2015 at 2:08pm
I can't help with any immuneotherapy but my wife had itchy eyes after finishing her Carboplatin/Gemzar chemo & her PCP is treating as "pink eye" and gave her drops yesterday fyi the Rx is antibiotic drops called Ciprofloxacin Hydrochloride.


Posted By: 123Donna
Date Posted: May 03 2016 at 10:34pm
Keytruda - Pembrolizumab Promising in Metastatic Triple-Negative Breast Cancer

Results from a phase Ib trial suggest that the programmed death 1 (PD-1) inhibitor pembrolizumab has activity and an acceptable toxicity profile as single-agent therapy in heavily pretreated, advanced triple-negative breast cancer (TNBC). 

“TNBC tumors are frequently of high histological grade, present at an advanced stage, are typically more aggressive and difficult to treat than hormone receptor–positive tumors, and are associated with a higher risk of early relapse,” wrote study authors led by Rita Nanda, MD, of the University of Chicago. “Given the suboptimal outcomes with chemotherapy, new targeted therapies for TNBC are urgently needed.”

Previous research has suggested that immunotherapy may provide benefit in TNBC. The new study, called KEYNOTE-012, was a nonrandomized phase Ib trial of pembrolizumab, which included a number of malignancies; this analysis focused on the 32 TNBC patients who were positive for the PD-1 ligand PD-L1. The results were  http://jco.ascopubs.org/content/early/2016/04/27/JCO.2015.64.8931.abstract" rel="nofollow - published  in the Journal of Clinical Oncology.

This was a heavily pretreated population, with 46.9% of patients having received at least three lines of therapy for metastatic disease, and 25.0% having received at least five lines. The median age in the study was 50.5 years.

Of the 32 patients included, 37.5% experienced some decrease in tumor burden from baseline. Twenty-seven of the patients met protocol-specified inclusion criteria for the efficacy analysis, and in those patients the overall response rate was 18.5%. One patient (3.7%) had a complete response, four had a partial response (14.8%), seven had stable disease (25.9%), and 13 patients had progressive disease (48.1%). The overall disease control rate (complete or partial response or stable disease for at least 24 weeks) was 25.9%.

Most patients (56.3%) experienced some treatment-related toxicity, and 15.6% had at least one grade 3 or higher adverse event (AE). The most common treatment-related AEs were arthralgia (18.8%), fatigue (18.8%), myalgia (18.8%), and nausea (15.6%). The grade 3 AEs included anemia, aseptic meningitis, lymphopenia, headache, and pyrexia. One patient died due to a treatment-related AE, a combination of disseminated intravascular coagulation and grade 4 decreased blood fibrinogen. Onset of this event occurred 10 days after the initial pembrolizumab dose.

The authors found that there was evidence of increasing probability of response with pembrolizumab with increasing expression of PD-L1, but they noted the small population size limits that finding’s significance. The 18.5% overall response rate was similar to other subsets of the KEYNOTE-012 study, including head and neck cancer patients (21.4%) and gastric cancer patients (22.2%).

“Overall, these results support further development of pembrolizumab for the treatment of metastatic TNBC,” the authors concluded. A phase II trial ( https://clinicaltrials.gov/ct2/show/NCT02447003" rel="nofollow - KEYNOTE-086 ) is currently enrolling TNBC patients to test this therapy, and other studies that will combine the PD-1 inhibitor with other therapies are also in development.


http://www.cancernetwork.com/breast-cancer/pembrolizumab-promising-metastatic-triple-negative-breast-cancer" rel="nofollow - http://www.cancernetwork.com/breast-cancer/pembrolizumab-promising-metastatic-triple-negative-breast-cancer




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: May 11 2016 at 9:19pm
Antibody appears to attack cancer cells, leaving other cells unscathed
An antibody has been developed from the body's own immune system that preferentially attacks cancer cells. The antibody works by targeting a natural defense mechanism that cancer tumors exploit. Cells in the body essentially use a home security system that relies on certain proteins to protect the cell surface and keep it safe. These proteins help the cell avoid injury and even death from unwanted activation of the immune system.

A research team from Duke Health has developed an antibody from the body's own immune system that preferentially attacks cancer cells.

The antibody works by targeting a natural defense mechanism that cancer tumors exploit.

Cells in the body essentially use a home security system that relies on certain proteins to protect the cell surface and keep it safe. These proteins help the cell avoid injury and even death from unwanted activation of the immune system.

In a paper published online May 5, 2016 in Cell Reports, the Duke team describes the workings of a cancer-fighting antibody they discovered, developed and tested in cell lines and animal models. The antibody dismantles a specific part of a cancer cell's defense system and then employs several mechanisms of attack.

"This is the first completely human-derived antibody developed as an anti-cancer therapy, which is very different from other immunotherapy approaches," said senior author Edward F. Patz, Jr., M.D., the James and Alice Chen Professor of Radiology and professor in the Department of Pharmacology and Cancer Biology at Duke.

Patz and colleagues -- including principals from the Duke Human Vaccine Institute who have been advancing the development of antibodies for an HIV vaccine -- started with the observation that some lung cancer patients have early-stage tumors that never progress to advanced disease.

One of the features that separated these patients from those who had more lethal tumors was the presence of antibodies against a protein called complement factor H, or CFH, which protects cells from an immune system attack.

CFH works by preventing activation of an important immune response. It inhibits the deposit of a complement C3b protein on the cell surface. Complement C3b initiates the degradation of the cell membrane, which eventually leads to cell death.

Once the antibody for CFH was identified, Patz and colleagues sought to explore how this immune response could be optimized as a cancer therapy. Critical to that effort was finding a way to produce antibodies that recognized the exact same part of CFH as the autoantibodies made by the early-stage cancer patients, thus assuring that the antibodies would have a particular affinity for cancer cells.

Patz and colleagues pooled the white blood cells from CFH antibody-producing cancer patients and then isolated and cloned the antibody genes from single immune cells that make the specific antibodies.

This was an efficient process that enabled the researchers to produce mature antibodies that recognized the same region of CFH targeted by the original patient's immune systems -- therefore leading to the attack of cancer cells, not healthy cells.

The researchers then tested the antibodies in multiple cancer cell lines, including lung, gastric and breast cancers in lab dishes, and in tumors in living mice. They found that the antibodies caused tumor cell death without any obvious side effects. The antibodies also appeared to trigger an additional adaptive immune response when the damaged cells sent signals to recruit an army of lymphocytes, creating a potentially more lethal systemic attack.

"We believe it might be this additional cellular response that could potentially have the most profound impact on cancer outcomes long-term," Patz said, noting that further tests would be required to understand the full potential of the approach.

"This could represent a whole new approach to treating cancer, and it's exciting because the antibody selectively kills tumor cells, so we don't have significant side effects to achieve tumor control," Patz said. "We believe we can modulate the immune response and let the body's own immune system take over to either kill the tumor or keep it from growing."

http://www.sciencedaily.com/releases/2016/05/160505133907.htm" rel="nofollow - http://www.sciencedaily.com/releases/2016/05/160505133907.htm



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jan 09 2017 at 8:51pm
A class of drugs already approved for the treatment of estrogen receptor-positive breast cancer may also have the potential to halt the spread of hard-to-treat, triple-negative breast cancer, a new study finds. . . .

. . . .Now, study co-author Dr. Matthew Goetz, leader of the Women's Cancer Program at Mayo Clinic in Rochester, MN, and colleagues suggest that CDK 4/6 inhibitors may also be effective for the treatment of triple-negative breast cancer.

CDK 4/6 inhibitors reduced triple-negative breast cancer metastasis

Triple-negative breast cancer accounts for around  http://www.breastcancer.org/symptoms/diagnosis/trip_neg" rel="nofollow - 10-20 percent  of breast cancers.

In triple-negative breast cancer, cancer cells are absent of estrogen, progesterone, and HER2 receptors. As such, the cancer does not respond to therapies that target these receptors, making it more difficult to treat.

According to Dr. Goetz and colleagues, previous research has shown that CDK 4/6 inhibitors are ineffective in reducing the growth of cancer cells in triple-negative breast cancer.

While the new study confirmed these findings, the team found that CDK 4/6 inhibitors may be effective for halting the spread of cancer cells to other areas of the body - otherwise known as cancer metastasis - in triple-negative breast cancer.

The researchers came to their  http://www.nature.com/articles/ncomms13923" rel="nofollow - findings  by testing CDK 4/6 inhibitors in a number of triple-negative breast cancer models, including "patient-derived xenografts," which are immunodeficient mouse models implanted with human  http://www.medicalnewstoday.com/articles/249141.php" rel="nofollow - tumor  tissue.

The team found that while CDK 4/6 inhibitors did not halt the growth of triple-negative breast cancer cells, the drugs significantly reduced the spread of cancer cells to distant organs by targeting a protein called SNAIL, which is known to promote cancer metastasis.

According to the researchers, their study results indicate that CDK 4/6 inhibitors may be beneficial for patients with triple-negative breast cancer.

"These findings may provide a new treatment for the prevention of cancer metastasis. Mayo Clinic is now developing new studies that will focus on the role of CDK 4/6 inhibitors and their potential to inhibit cancer metastasis in women with triple-negative breast cancer who are at highest risk for cancer metastasis."

Dr. Matthew Goetz


http://www.medicalnewstoday.com/articles/315110.php" rel="nofollow - http://www.medicalnewstoday.com/articles/315110.php



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jun 03 2017 at 5:26pm
Tested on animals, but not on humans yet.
 

Combined use of two existing drugs appears to slow cancer's tendency to spread, study shows

A team led by Johns Hopkins researchers has discovered a biochemical signaling process that causes densely packed cancer cells to break away from a tumor and spread the disease elsewhere in the body. In their study, published online May 26 in Nature Communications, the team also reported that the combined use of two existing drugs disrupts this process and appears to significantly slow cancer's tendency to travel, a behavior called metastasis.

The new findings are important, the researchers said, because 90 percent of cancer deaths are caused by metastasis, and anything that derails this activity could improve the prognosis for patients. The crucial new signaling process turned up when the team took a closer look at cellular events that promote metastasis.

"We found that it was not the overall size of a primary tumor that caused cancer cells to spread, but how tightly those cells are jammed together when they break away from the tumor," said lead author Hasini Jayatilaka, a postdoctoral fellow at Johns Hopkins' Physical Sciences-Oncology Center. "At a fundamental level, we found that cell density is very important in triggering metastasis. It's like waiting for a table in a severely overcrowded restaurant and then getting a message that says you need to take your appetite elsewhere."

Jayatilaka and her colleagues found a medication mix that kept this microscopic message from being delivered. The team members cautioned that this treatment was tested in animal models, but not yet on human cancer patients. Nevertheless, they said the discovery contributes to a promising new focus for cancer research: disrupting the biochemical activity that prods cancer cells to spread through the body.

One of the study's senior authors, Denis Wirtz, who is Johns Hopkins University's vice provost for research and director of its Physical Sciences-Oncology Center, said no commercial drugs are now being produced specifically to inhibit metastasis because drug companies believe the best way to stop cancer from spreading is to destroy the primary tumor from which it originates.

"The pharmaceutical companies view metastasis as a by-product of tumor growth," said Wirtz, who also holds Johns Hopkins faculty appointments in chemical and biomolecular engineering, in pathology and at the Johns Hopkins Kimmel Cancer Center. "Our study looked more closely at the steps that actually initiate metastasis. By doing this, we were able to develop a unique therapeutic that directly targets metastasis, not the growth of the primary tumor. This treatment has the potential to inhibit metastasis and thus improve cancer patient outcomes."

The two key drivers of metastasis, Wirtz said, are cancer cells' tendency to reproduce at a rapid rate and their ability to move through surrounding tissue until they reach the bloodstream, where they can then hitch a ride to spread the disease to other parts of the body.

By studying tumor cells in a three-dimensional environment that resembles human tissue, the researchers were able to determine how these activities begin. The team discovered that as two types of cancer cells reproduced and created more crowded conditions in the test site, these cells secreted certain proteins that encouraged migration. The researchers identified these proteins as Interleukin 6 (IL-6) and Interleukin 8 (IL-8).

"IL-6 and IL-8 seem to deliver a message to cancer cells, telling them to move away from the densely populated primary tumor," said lead author Jayatilaka, who recently earned her doctorate in chemical and biomolecular engineering as a member of Wirtz's lab team and earlier received her undergraduate degree from Johns Hopkins' Whiting School of Engineering.

In the team's animal studies, the researchers found that applying two existing drugs--Tocilizumab and Reparaxin--blocked the receptors that enable cancer cells to get their relocation orders. Tocilizumab is an approved medication for rheumatoid arthritis and is in trials for use in ovarian cancer cases. Reparaxin is being evaluated as a possible treatment for breast cancer.

"In our eight-week experiment, when we used these two drugs together, the growth of the primary tumor itself was not stopped, but the spread of the cancer cells was significantly decreased," Jayatilaka said. "We discovered a new signaling pathway that, when blocked, could potentially curb cancer's ability to metastasize."

Source:

https://hub.jhu.edu/2017/05/26/cellular-target-cancer-spread/" rel="nofollow - https://hub.jhu.edu/2017/05/26/cellular-target-cancer-spread/
http://www.news-medical.net/news/20170526/Combined-use-of-two-existing-drugs-appears-to-slow-cancers-tendency-to-spread-study-shows.aspx" rel="nofollow - http://www.news-medical.net/news/20170526/Combined-use-of-two-existing-drugs-appears-to-slow-cancers-tendency-to-spread-study-shows.aspx



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jun 05 2017 at 9:47pm

Keytruda Shows Meaningful Clinical Benefit When Combined with Standard Therapy 


Two independent studies have added new evidence to the benefits of combined therapies with  http://www.merck.com/" rel="nofollow - Merck ‘s PD-1 inhibitor  https://www.keytruda.com/" rel="nofollow - Keytruda  (pembrolizumab) for the treatment of aggressive triple-negative breast cancer (TNBC).

Adding Keytruda to standard therapies for breast cancer improved the number of patients achieving a complete response to therapy.

The findings will be featured in a poster, “ http://abstracts.asco.org/199/AbstView_199_183215.html" rel="nofollow - Efficacy/safety of epacadostat plus pembrolizumab in triple-negative breast cancer and ovarian cancer: Phase I/II ECHO-202 study ,” to be presented at the  https://am.asco.org/" rel="nofollow - American Society of Clinical Oncology (ASCO) 2017 Annual Meeting , set for June 2-6 in Chicago.

Designed to target the  https://immuno-oncologynews.com/tag/pd-1/" rel="nofollow - PD-1  receptor, Keytruda is meant to improve the activity of immune T-cells capable of fighting cancer cells. Originally approved by the U.S. Food and Drug Administration (FDA) to treat melanoma, Keytruda has since won FDA approval for several other cancers, such as non-small cell lung cancer, head and neck squamous cell carcinoma, classical Hodgkin lymphoma (cHL), and bladder cancer.

Researchers at the University of Pennsylvania’s Abramson Cancer Center are currently studying the benefits of Keytruda for other cancer types, including TNBC. Their Phase 1/2 ECHO-202 trial ( https://clinicaltrials.gov/ct2/show/NCT02178722" rel="nofollow - NCT02178722 ) involved 39 patients with TNBC who received a combination of  https://immuno-oncologynews.com/keytruda-pembrolizumab/" rel="nofollow - Keytruda  and an investigational checkpoint inhibitor known as epacadostat, developed by  https://www.incyte.com/" rel="nofollow - Incyte .

Undergoing dose escalating evaluations, the combined therapy was found to be generally well-tolerated with no major adverse events being reported.

“In each patient group, the combination did not add any significant increase in side effects compared to what patients experience with the PD-1 inhibitor alone,” Dr. Tara Gangadhar, who led five of the new analyses from the ECHO-202 trial, said in a  https://medicalxpress.com/news/2017-05-multiple-cancers-pembrolizumab-combination-therapies.html" rel="nofollow - press release . Gangadhar is an assistant professor of hematology oncology at the university’s Perelman School of Medicine.


A second study, “ http://abstracts.asco.org/199/AbstView_199_194235.html" rel="nofollow - Pembrolizumab plus standard neoadjuvant therapy for high-risk breast cancer (BC): Results from I-SPY 2 ,” evaluated the clinical benefits of Keytruda plus standard of care, given before  https://breastcancer-news.com/breast-cancer-surgery/" rel="nofollow - surgery , to HER2-negative metastatic breast cancer.

The multicenter Phase 2 I-SPY 2 trial ( https://clinicaltrials.gov/ct2/show/NCT01042379" rel="nofollow - NCT01042379 ) included 69 women who received Keytruda plus Taxol ( https://breastcancer-news.com/albumin-bound-paclitaxel-nab-paclitaxel-or-abraxane/" rel="nofollow - paclitaxel ) or standard therapy with Taxol alone. The Keytruda-Taxol combo more than tripled TNBC patients’ complete response rate compared to Taxol alone.

Patients with hormone receptor positive breast cancer had a 28 percent complete response rate, compared to the 14.8 percent response rate among the control group.

“This is incredibly exciting news for patients with aggressive cancers and the beginning of generating new and better curative options at diagnosis,” said Angela DeMichele, chair of trial operations for the study. “These findings reflect a growing body of knowledge about how these drugs interact with the immune system that will lead to safer use of PD-1 inhibitors in future studies.”

http://breastcancer-news.com/2017/06/01/keytruda-improves-aggressive-breast-cancer-response-to-standard-therapy" rel="nofollow - http://breastcancer-news.com/2017/06/01/keytruda-improves-aggressive-breast-cancer-response-to-standard-therapy



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: mainsailset
Date Posted: Jun 06 2017 at 11:20am
'more than tripled the response' is a huge breakthrough and because Keytruda already has a track record I'm hopeful that it will join the lineup of drug therapies already approved soon.

All the more reason to keep up on these breakthroughs for everyone looking at treatment because it's good to go over these options with your oncology team as they just might be the treatment that saves your life!

Here's another article, check out the clinical trials

https://seekingalpha.com/article/4079115-lynparza-gets-parp-edge-breast-cancer" rel="nofollow - https://seekingalpha.com/article/4079115-lynparza-gets-parp-edge-breast-cancer

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dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear


Posted By: 123Donna
Date Posted: Jun 09 2017 at 11:26am
This study is game changing - instead of trying to treat one type of cancer, they looked at the uniqueness of the responders to see what they had in common.

Cancer Drug Proves to Be Effective Against Multiple Tumors

The new study was based on a different idea. The immune system can recognize cancer cells as foreign and destroy them. But tumors deflect the attack by shielding proteins on their surface, making them invisible to the immune system.

Pembroluzimab is a new type of immunotherapy drug known as a PD-1 blocker, which unmasks the cancer cells so that the immune system can find and destroy them.

The drug is the happy result of a failed trial. A nearly identical drug, nivolumab, was given to 33 colon cancer patients, and just one showed any response — but his cancer vanished altogether.

What was special about that one patient? Dr. Diaz, a geneticist at Johns Hopkins until now, and lead author of the new study, found the answer: a genetic mutation that prevented the tumor from repairing DNA damage.

As a result, the man’s cancer cells contained a plethora of mutated genes, which produced thousands of strange-looking proteins on the surfaces of the cells. Once the tumor’s cloaking mechanism was short-circuited by the drug, the man’s immune system had no trouble targeting the foreign proteins on the cancer cells.

That led to the idea for the Dr. Diaz’s new study. He and his colleagues sought patients whose tumors had the same genetic defect, which can arise in any of four genes in a pathway that repairs damaged DNA. They gave these patients a PD-1 blocker and were surprised by the results.

The drug’s effects have been so durable that the investigators do not know how long the results should be expected to persist or how long these patients might expect to survive. That kind of result, Dr. Baselga said, “is insane.”

One patient in the study, Adrienne Skinner, 60, of Larchmont, N.Y., had an extraordinarily rare and deadly cancer, ampullary cancer, that arises at the end of the bile duct. There is no standard treatment, and the prognosis is dire.

Her doctors scheduled her for a drastic surgery that removes part of the pancreas, part of the small intestine, and the gall bladder. But her surgeon canceled the operation when he discovered her cancer had invaded her liver.

She tried chemotherapy instead — six months of one kind, then six months of another. Neither worked.

Then she qualified for Dr. Diaz’s clinical trial at Johns Hopkins. On April 15, 2014, Ms. Skinner had her first dose of the drug.

In July, her doctor inserted an endoscope for another biopsy. He turned to Ms. Skinner and said, “If someone hadn’t told me you have ampullary cancer, I would not have known.” The tumor was gone.

The trial involved giving patients the drug for two years, so Ms. Skinner continued to take the drug as a sort of insurance. Last year, she stopped, and her cancer has not returned.

“In effect, I was cured within months,” she said. “I have a great life.”

But even this promising trial has left a thread dangling: Why didn’t all of the patients respond?

There is now a fervid search for the answer. “Multiple labs are looking like crazy,” Dr. Balsega said.
http://www.nytimes.com/2017/06/08/health/cancer-drug-keytruda-tumors.html" rel="nofollow - http://www.nytimes.com/2017/06/08/health/cancer-drug-keytruda-tumors.html



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jun 16 2017 at 9:58am
Results from I-SPY 2 clinical trial has found that adding the drug pembrolizumab (Keytruda) in combination with standard therapy before surgery shows potential for meaningful outcomes in patients with locally advanced triple negative (TNBC) or hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancers.

http://www.uab.edu/medicine/news/latest/item/1558-data-from-i-spy-2-trial-shows-potential-of-a-new-precision-medicine-drug-therapy-for-breast-cancer-patients" rel="nofollow - http://www.uab.edu/medicine/news/latest/item/1558-data-from-i-spy-2-trial-shows-potential-of-a-new-precision-medicine-drug-therapy-for-breast-cancer-patients


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Aug 16 2017 at 8:07pm

Triple Negative Breast Cancer Patients Who Responded to Immunotherapy Had Long-term Survival Benefit

Among patients with metastatic triple-negative breast cancer (TNBC) who were treated with the anti-PD-L1 cancer immunotherapy Tecentriq (atezolizumab), those who responded to the medicine lived significantly longer compared with those who did not respond, according to data from a small clinical study presented at the American Association of Cancer Research annual meeting.

About Triple Negative Breast Cancer

Approximately 12% of breast cancers are triple-negative breast cancers, meaning that they are estrogen-receptor negative (ER-), progesterone-receptor negative (PR-), and human epidermal growth factor receptor 2-negative (HER2-). This means that TNBC is not stimulated to grow from exposure to the female hormones estrogen or progesterone, nor through an overactive HER2 pathway.

Unfortunately, many available and effective treatment options for the majority of breast cancers block the growth stimulating effects of ER, PR and/or HER2; therefore, TNBC has limited therapeutic options.

In addition, TNBC tends to be an aggressive type of cancer, tends to be diagnosed at a more advanced stage, and proportionately affects younger women more often than other breast cancers. Novel treatment options for TNBC have lagged behind that of other types of breast cancers.

About Tecentriq

Tecentriq is an agent that helps to restore the body’s immune system in fighting cancer. It creates its anti-cancer effects by blocking a specific protein that is used by cancer cells to escape an attack by the immune system, called PD-L1. Once PD-L1 is blocked, cells of the immune system are able to identify cancer cells as a threat, and initiate an attack to destroy the cancer. Tecentriq and other “checkpoint inhibitors” have been approved for the treatment of several cancers recently.

In the current clinical study evaluating Tecentriq in patients with TNBC, the most significant findings were the difference in the overall survival between patients who responded to Tecentriq and patients who did not respond, and the prolonged average duration of response; 21 months, which is substantially longer than what has been seen with other treatments. All responders were alive after one year and the one-year survival rate for nonresponders was only 38 percent.

Immune therapy with checkpoint inhibitors appears to be a promising treatment approach for individuals with TNBC whether used alone or in combination with other therapies.2,3

References:

  1. https://twitter.com/hashtag/AACR17?src=hash" rel="nofollow - #AACR17
  2. http://news.cancerconnect.com/keytrudahalaven-combo-may-effective-advanced-triple-negative-breast-cancer/" rel="nofollow - http://news.cancerconnect.com/keytrudahalaven-combo-may-effective-advanced-triple-negative-breast-cancer/
  3. http://news.cancerconnect.com/tecentriq-plus-abraxane-effective-combo-difficult-treat-breast-cancer/" rel="nofollow - http://news.cancerconnect.com/tecentriq-plus-abraxane-effective-combo-difficult-treat-breast-cancer/

    http://news.cancerconnect.com/triple-negative-breast-cancer-patients-responded-immunotherapy-long-term-survival-benefit/" rel="nofollow - http://news.cancerconnect.com/triple-negative-breast-cancer-patients-responded-immunotherapy-long-term-survival-benefit/


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Aug 17 2017 at 6:41pm
Cancer Drugs That Halt Tumors Can Also Shrink Them

A class of drugs known as CDK4/6 inhibitors, which have been approved for treating some types of breast cancer, may have much more to offer than previously thought. Not only can they stop tumors from growing by halting cell division, but they can also "spur the immune system to attack and shrink" them.

This was the main finding of a new study from the Dana-Farber Cancer Institute and Brigham and Women's Hospital, both in Boston, MA, the results of which have been published in the journal Nature.

CDK4/6 inhibitors are a class of drugs that work by blocking certain proteins called cyclin-dependent kinases (CDKs) 4 and 6, which promote the growth of  http://www.medicalnewstoday.com/info/cancer-oncology/" rel="nofollow - cancer  cells.

At present, these drugs have only been approved for treating some patients with metastatic breast cancer, "but they've also shown promise against others types of tumors in clinical trials," says co-first author Shom Goel, Ph.D., of the Dana-Farber Cancer Institute.

Shrink as well as halt tumors

Dr. Goel says that in early clinical trials of CDK4/6 inhibitors in breast cancer patients, they noticed that not only did the tumors stop growing - as you might expect with drugs that arrest cell division - but they also shrank, "sometimes quite dramatically."

He and his colleagues believe that scientists are only just beginning to discover the full potential of what CDK4/6 inhibitors may have to offer.

In  http://dx.doi.org/10.1038/nature23465" rel="nofollow - their study , the researchers found that not only did the drugs stop cancer cells dividing, but they also promoted anti-cancer immunity in two ways.

One way was by getting cancer cells to increase their display of abnormal proteins on their surfaces, which made it easier for the immune system to find and destroy them.

Another way that the CDK4/6 inhibitors helped the immune system to attack tumors was by reducing immune cells called T regulatory cells (Tregs). Tregs usually dampen immune response, so the fewer there are, the fiercer the attack.

The team discovered the tumor-halting and tumor-shrinking effects when they treated mice with breast cancer and other solid tumors with the CDK4/6 inhibitor abemaciclib. The experimental drug  http://www.prnewswire.com/news-releases/fda-grants-priority-review-for-lillys-abemaciclib-for-the-treatment-of-advanced-breast-cancer-300484992.html" rel="nofollow - recently received  priority status from the U.S. Food and Drug Administration (FDA).

Confirmed in human samples

When they analyzed biopsy samples from women taking part in a clinical trial testing a CDK4/6 inhibitor for breast cancer, the researchers observed the same effects that they saw in the mice; not only did the drug halt the  http://www.medicalnewstoday.com/articles/249141.php" rel="nofollow - tumor  cell cycle, but it also spurred the immune system to attack the tumors.

The authors explain that clinical trials show that around 20 percent of breast cancer patients treated just with abemaciclib show a "significant response," while another 20 to 30 percent experience "stabilizations of tumor growth." These effects emerge within 4 months of starting on the drug.

Dr. Goel and colleagues also found that the anti-cancer effect was even stronger when they coupled the CDK4/6 inhibitors with other immunotherapy drugs known as checkpoint inhibitors, which can stop cancer cells evading the immune system.

"It appears that the CDK4/6 inhibitors might be able to sensitize some patients' cancers to the anti-tumor effects of immune checkpoint inhibitors. The result might be especially encouraging for breast cancer patients, who have derived little benefit from immunotherapy in trials conducted to date."

The team says that more work should be done to discover why CDK4/6 inhibitors appear to benefit some patients more than others. They also hope that their findings will encourage others to look at how to combine CDK4/6 inhibitors with different immunotherapies.

http://www.medicalnewstoday.com/articles/319013.php" rel="nofollow - http://www.medicalnewstoday.com/articles/319013.php





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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: Sarahlou
Date Posted: Aug 18 2017 at 10:00pm
A friend is in a clinical trial using Keytruda and has had success with it shrinking her tumor. She has TNBC.


Posted By: 123Donna
Date Posted: Aug 31 2017 at 8:47am

Study sheds light on why some breast cancers have limited response to immunotherapy

UNC Lineberger Comprehensive Cancer Center researchers have identified a possible reason why some aggressive breast cancers are unresponsive to certain immunotherapy treatments, as well as a potential solution.

In the Journal of Clinical Investigation, researchers report on their study that explored a perplexing question: Why were drugs designed to unleash the immune system against cancer ineffective in a type of triple negative breast cancer with a heavy presence of immune cells? Their findings could lead to a strategy to improve immunotherapy responses in the "claudin-low" subtype of breast cancer.

"We were trying to figure out why a tumor made up, in some instances, of half immune cells doesn't respond to a treatment that should ramp up immune cells present in the tumor," said the study's senior author Jonathan Serody, MD, UNC Lineberger member and the Elizabeth Thomas Professor in the UNC School of Medicine. "I think it's important for us to try to start segregating out the types of tumors that don't respond to these treatments at a much granular genomic level, and try to figure out new mechanisms to enhance the response rate to immunotherapy."

The American Cancer Society estimates that approximately 12 percent of breast cancers are "triple negative," meaning they lack three cell surface receptors that are known to help drive the cancer. Triple negative breast cancer tumors typically grow faster and come back sooner than other breast cancer types. There are no targeted treatments for these cancers.

In a subset of triple negative breast cancers known as "claudin low," researchers found an elevated level of immune cells in and around the tumors. They believed this would help the body fight the cancer. However, the researchers found the opposite: "Checkpoint inhibitors," a type of immunotherapy that works by unlocking the immune system's brakes against cancer, were ineffective in this subtype.

They determined with gene expression analysis that, instead of being flooded with immune cells that attack cancer tumors, claudin-low tumors had a high concentration of regulatory T-cells - a type of immune cell that suppresses the body's defenses. Claudin-low tumors were releasing a chemical signal to attract these regulatory T-cells.

"This regulatory T-cell population is preventing the immune system from rejecting the cancer," said UNC Lineberger's Benjamin Vincent, MD, an assistant professor in the UNC School of Medicine. "We thought if we could get rid of those cells, we could help the immune system better fight the breast cancer cells."

In an effort to allow the immune-stimulating cancer treatments to work, the researchers tested an investigational approach to deplete the regulatory T-cells, and they combined the treatment with a checkpoint inhibitor in order to try to improve outcomes. This combination slowed tumor growth. They believe they have identified a key aspect of what is preventing immunotherapy treatments from working.

"This finding may shed some light on why response rates to immunotherapy treatments remain low in triple negative breast cancer," Vincent said. "We are looking to understand why patients who don't respond don't respond, and what we can do to render their tumors immunotherapy responsive."

Vincent is helping to lead a clinical trial testing this strategy to improve responses to checkpoint inhibitors. Researchers also believe these findings may also underscore the need to study other cancer types at a genomic level to understand differences in response rates to immunotherapy treatments.

"This speaks to the mission of UNC Lineberger, which is to conduct groundbreaking basic science research, but always with the mission of extending and improving the lives of patients as our end goal," Vincent said.


https://medicalxpress.com/news/2017-08-immune-cells-contribute-treatment-resistance.html" rel="nofollow - https://medicalxpress.com/news/2017-08-immune-cells-contribute-treatment-resistance.html



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: mainsailset
Date Posted: Aug 31 2017 at 10:56am
Donna, I saw that report this morning and it's so interesting and a good reminder how now more than ever it's important for our medical teams to id all the characteristics of our particular tumor to determine what choices in treatment can be made. Amazing to me to see the researchers perplexed by the finding that the Claudin low tumors reacted the opposite of what they expected.


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dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear


Posted By: 1maJ
Date Posted: Sep 04 2017 at 10:22pm
Hi Donna, thanks for posting all this info on new research.  I came back to the forum to look for the latest on TNBC treatments, and this gives me hope and calms me down.  I am 2 years out from diagnosis, the time when most women have their recurrence, so I am finding myself to have a bit more anxiety than I would like.  Every little headache is a reminder that something could be brewing :(  But I am doing fine though, and enjoying life more than ever :)

Thanks!

Ima


Posted By: 123Donna
Date Posted: Oct 25 2017 at 11:14pm
Adoptive T Cell Therapy 

http://theconversation.com/a-new-clue-into-treatments-for-triple-negative-breast-cancer-a-mean-disease-85379" rel="nofollow - http://theconversation.com/a-new-clue-into-treatments-for-triple-negative-breast-cancer-a-mean-disease-85379




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Dec 21 2017 at 8:02am

According to new research out of the Case Comprehensive Cancer Center at Case Western Reserve University School of Medicine. In the Proceedings of the National Academy of Sciences, researchers showed triple-negative breast cancer cells are highly vulnerable to interferon-β-;a potent antimicrobial that also activates the immune system. The new study shows interferon-β impairs breast cancer cells' ability to migrate and form tumors. The study also suggests interferon-β treatment could improve outcomes for certain breast cancer patients.

"We demonstrate that interferon-β reverses some of the more aggressive features of triple-negative breast cancer, which are responsible for metastasis and therapy-failure," said Mary Doherty, first author and pathology graduate student at Case Western Reserve School of Medicine. "Moreover, we found that evidence of interferon-β in triple-negative breast cancer tumors correlates with improved patient survival following chemotherapy.

To read the entire article:
https://www.news-medical.net/news/20171218/Study-suggests-new-treatment-option-for-most-lethal-form-of-breast-cancer.aspx" rel="nofollow - https://www.news-medical.net/news/20171218/Study-suggests-new-treatment-option-for-most-lethal-form-of-breast-cancer.aspx


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Feb 15 2018 at 7:06pm

Triple-negative Breast Cancer Patients Who Responded to Immunotherapy Had Long-term Survival Benefit

Among patients with metastatic triple-negative breast cancer (TNBC) who were treated with the anti-PD-L1 cancer immunotherapy Tecentriq (atezolizumab), those who responded to the medicine lived significantly longer compared with those who did not respond, according to data from a small clinical study presented at the American Association of Cancer Research annual meeting.

About Tecentriq

Tecentriq is an agent that helps to restore the body’s immune system in fighting cancer. It creates its anti-cancer effects by blocking a specific protein that is used by cancer cells to escape an attack by the immune system, called PD-L1. Once PD-L1 is blocked, cells of the immune system are able to identify cancer cells as a threat, and initiate an attack to destroy the cancer. Tecentriq and other “checkpoint inhibitors” have been approved for the treatment of several cancers recently.

In the current clinical study evaluating Tecentriq in patients with TNBC, the most significant findings were the difference in the overall survival between patients who responded to Tecentriq and patients who did not respond, and the prolonged average duration of response; 21 months, which is substantially longer than what has been seen with other treatments. All responders were alive after one year and the one-year survival rate for nonresponders was only 38 percent.

Immune therapy with checkpoint inhibitors appears to be a promising treatment approach for individuals with TNBC whether used alone or in combination with other therapies.2,3

http://news.cancerconnect.com/triple-negative-breast-cancer-patients-responded-immunotherapy-long-term-survival-benefit/" rel="nofollow - http://news.cancerconnect.com/triple-negative-breast-cancer-patients-responded-immunotherapy-long-term-survival-benefit/



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Feb 21 2018 at 6:37pm

Newly Identified Potential Therapeutic Approach Kills Triple-Negative Breast Cancer Cells in Pre-Clinical Study

Findings suggests potential new area of focus for checkpoint blockade immunotherapy


Triple-negative breast cancer (TNBC), a highly aggressive, relapse-prone cancer that accounts for one-fourth of all breast cancers, could be the focus of a new area of study for immune checkpoint blockade therapy.  A team of researchers at The University of Texas MD Anderson Cancer Center revealed that in TNBC a cell process called glycosylation is required for PD-L1/PD1 molecules to interact and identified exactly how and why glycosylation is so crucial. Findings from the study were published in the Feb. 12 issue of  http://www.cell.com/cancer-cell/home" rel="nofollow - Cancer Cell .

Immune checkpoint blockade therapy relies on connections between PD-L1 and its sister molecule, PD1, found on T-cell surfaces, allowing cancer cells to go undetected by the immune system. Blocking PD-L1 and PD-1 interaction has been the basis for successful immunotherapies already in use in other cancers.

“Glycosylation is a process that attaches portions of sugar molecules called moieties to the protein providing it fuel to grow and spread,” said  https://faculty.mdanderson.org/profiles/mien-chie_hung.html" rel="nofollow - Mien-Chie Hung, Ph.D. , chair of  https://www.mdanderson.org/research/departments-labs-institutes/departments-divisions/molecular-and-cellular-oncology.html" rel="nofollow - Molecular and Cellular Oncology . “Glycosylation of PD-L1 in tumor cells stabilizes PD-L1, but it is largely unknown whether sugar moiety by itself is required for binding to PD-1 to suppress anti-tumor immunity.”

Hung’s research group shed further light in this area through discovery of glycosylated PD-L1 (gPD-L1), and worked with STCube Pharmaceuticals, Inc. to develop anti-gPD-L1 antibodies that recognize this glycosylated form of PD-L1, killing tumor cells while not harming healthy ones.

To improve the therapeutic efficacy of anti-gPD-l1 antibody, the team linked a potent small molecule chemotherapy agent, called MMAE, to the anti-gPD-L1, creating a new antibody drug conjugate (ADC), called anti-gPD-L1-MMAE, which resulted in higher therapeutic efficacy in animal models. Hung believes the development of this glycosylated PD-L1 ADC (anti-gPD-L1-MMAE) may represent a new generation of immunotherapy that is more targeted with fewer adverse effects.

“We demonstrated that gPD-L1 is an excellent candidate for ADC as sugar moiety is critical for PD-L1’s detrimental role in TNBC,” said Hung. “Immune checkpoint blockade treatment options remains limited in TNBC, so identifying new immune checkpoint targets to improve upon current therapy is urgently needed.”

https://newswise.com/articles/newly-identified-potential-therapeutic-approach-kills-triple-negative-breast-cancer-cells-in-pre-clinical-study" rel="nofollow - https://newswise.com/articles/newly-identified-potential-therapeutic-approach-kills-triple-negative-breast-cancer-cells-in-pre-clinical-study



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Mar 23 2018 at 1:05pm
More research needed, but looks promising.

Groundbreaking research has revealed a promising strategy to stop the recurrence of cancer, and it comes in the form of a biodegradable gel.

Created by scientists at the Dana-Farber Cancer Institute in Boston, MA, the gel was designed to deliver immunotherapy directly to the area from which a cancerous  https://www.medicalnewstoday.com/articles/249141.php" rel="nofollow - tumor  has been surgically removed.

Upon testing the gel on mice during the surgical removal of  https://www.medicalnewstoday.com/articles/37136.php" rel="nofollow - breast cancer  tumors, the scientists found that it not only helped to prevent tumor recurrence at the primary site, but that it also eliminated secondary tumors in the lungs. . . .

. . .'Encouraging' results

For their study, Goldberg and team tested the gel in mice that underwent the surgical removal of breast cancer tumors. The team made the decision to use the gel directly after tumor removal, rather than before.

"We reasoned," Goldberg explains, "that it would be easier to eliminate a small number of residual cancer cells by creating an immunostimulatory environment than it would be to treat an intact primary tumor, which has many means of evading an immune system attack."

Several months after surgery, the mice treated with the gel were much less likely to experience tumor regrowth, compared with rodents that received conventional immunotherapy delivery.

When the researchers injected breast cancer cells into the side opposite to where the original tumor was removed, the gel-treated rodents showed no signs of tumor formation.

Also, the study found that the gel eradicated secondary tumors in the lungs of the mice — that is, it eliminated lung tumors formed from breast cancer cells that had spread from the primary site.

The researchers also replicated their findings in mice with primary lung cancer and  https://www.medicalnewstoday.com/articles/154322.php" rel="nofollow - melanoma , which is a deadly form of  https://www.medicalnewstoday.com/articles/154322.php" rel="nofollow - skin cancer .

Based on their results, Goldberg and colleagues believe that their gel-based immunotherapy could be an effective treatment strategy against a number of different cancers.

"This approach has the potential to deliver immunotherapy in a manner that focuses the therapy at the site of interest during a critical time window," he says.

"We are extremely encouraged by the results of this study and hope that this technology will be adapted for patients for testing in clinical trials in the not-too-distant future."

Michael Goldberg, Ph.D.



https://www.medicalnewstoday.com/articles/321307.php" rel="nofollow - https://www.medicalnewstoday.com/articles/321307.php



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jun 25 2018 at 7:06pm

Zejula-Keytruda Shows Promising Response Rates for Triple-negative Breast Cancer in Phase 1/2 Trial


A combination of  https://www.keytruda.com/" rel="nofollow - Keytruda  (pembrolizumab) and https://www.zejula.com/en" rel="nofollow - Zejula (niraparib) has shown promising and durable response rates in triple-negative breast cancer patients, regardless of their BRCA mutational status, Phase 1/2 trial data show.

The trial, called TOPACIO ( http://clinicaltrials.gov/show/NCT02657889" rel="nofollow - NCT02657889 ), is assessing the combination in triple-negative breast cancer patients with advanced or metastatic disease and in women with ovarian cancer.

Results from the breast cancer group were recently presented at the https://am.asco.org/" rel="nofollow - 2018 American Society of Clinical Oncology Annual Meeting , in an oral presentation, titled “ http://abstracts.asco.org/214/AbstView_214_213387.html" rel="nofollow - TOPACIO/Keynote-162: Niraparib + pembrolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC), a phase 2 trial .”

PARP enzymes act as DNA damage sensors, binding to the sites of DNA damage and contributing to their repair. Cancer cells that have defects in other DNA repair mechanisms — such as those with mutated BRCA tumor suppressor genes — rely on PARP to survive and proliferate.

Zejula, developed by  http://www.tesarobio.com/" rel="nofollow - TESARO , is a PARP inhibitor that leads to the accumulation of DNA damage and ultimately to the death of these cancer cells.

The medicine is already approved as a maintenance therapy for ovarian cancer patients, and has shown promise in breast cancer patients with mutations in the BRCA genes.

Keytruda, developed by http://www.merck.com/index.html" rel="nofollow - Merck , has been https://breastcancer-news.com/2017/06/09/keytruda-effective-patients-metastatic-triple-negative-breast-cancer/" rel="nofollow - shown to induce responses in 5-18% of triple-negative breast cancer patients, which led researchers to test a combination of both agents.

TOPACIO is a Phase 1/2 trial assessing if Keytruda and Zejula together can increase response rates in patients with advanced or metastatic triple-negative breast cancer (TNBC) and recurrent ovarian cancer.

http://ir.tesarobio.com/static-files/ff92ae6b-5f1c-4de9-88a9-7fd1862824bd" rel="nofollow - As of April 2018 , 46 of the TNBC patients were able to be assessed for an initial response. Among them, 15 had BRCA mutations, and five had genetic alterations in other DNA repair genes.

http://ir.tesarobio.com/static-files/ff92ae6b-5f1c-4de9-88a9-7fd1862824bd" rel="nofollow - To date , three patients had complete responses, 10 had partial tumor reductions, and 10 had their disease stabilized with the treatment. This represents an overall response rate of 28% and a disease control rate of 50%.

As expected, patients with BRCA mutations had the best response rates, at 60%, followed by those with mutations in other DNA repair genes, at 55%, and those who were positive for the PD-L1 protein — a biomarker that predicts response to Keytruda — at 36%.

Overall, the 15 patients with BRCA mutations lived for a median of 8.3 months without their disease progressing, which is better than the three to five months seen with standard https://breastcancer-news.com/chemotherapy/" rel="nofollow - chemotherapy , or the rates seen with either agent alone.

The study is ongoing, with eight of the responders still receiving the combination, including five patients who experienced a beneficial clinical effect for approximately one year.

In general the treatment has been well-tolerated, with the most common serious events being anemia and reduced blood platelet levels.

http://breastcancer-news.com/2018/06/18/zejula-keytruda-promising-response-rates-phase-1-2-trial-breast-cancer" rel="nofollow - http://breastcancer-news.com/2018/06/18/zejula-keytruda-promising-response-rates-phase-1-2-trial-breast-cancer



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Aug 27 2018 at 6:26pm

NCI Awards $2.3M Grant to Advance Possible Therapy for Triple-negative Breast Cancer


The https://www.nih.gov/about-nih/what-we-do/nih-almanac/national-cancer-institute-nci" rel="nofollow - National Cancer Institute has awarded a Fast Track  https://www.sbir.gov/about/about-sbir" rel="nofollow - Small Business Innovation Research grant to http://www.agilvax.com/" rel="nofollow - Agilvax to support development of the company’s lead immunotherapy candidate, AX09, for an aggressive and difficult-to-treat  https://breastcancer-news.com/breast-cancer-overview/" rel="nofollow - breast cancer .

The grant, worth about $2.3 million, will go toward preclinical trials, a toxicology study, and the establishment of good manufacturing practices. Ultimately, it aims to enable the submission of AX09’s investigational new drug application (IND) to the https://www.fda.gov/" rel="nofollow - U.S. Food and Drug Administration  to begin clinical testing.

The three most common types of receptors that fuel breast cancer growth are the estrogen, progesterone, and HER2. In some 20 percent of breast cancer patients, whose cancer is called triple-negative, these receptors are not present in the tumor.

In these patients, treatments like https://breastcancer-news.com/hormone-therapy/" rel="nofollow - hormone therapy or those that target estrogen, progesterone, and HER-2 are ineffective. Triple-negative breast cancer (TNBC) also tends to be more aggressive.

AX09 is a virus-like-particle immunotherapy aiming to treat TNBC. It targets the stem cell protein xCT, found in a high percentage of breast cancers including TNBC.

“We are delighted to receive this grant award from the National Cancer Institute (NCI) to advance the development of AX09 in TNBC, which is one of the lead indications for this product,” Federica Pericle, PhD, president and chief executive officer of Agilvax, said in a https://www.businesswire.com/news/home/20180807005092/en/Agilvax-Awarded-2.3-Million-SBIR-Fast-Track4" rel="nofollow - news release . “The SBIR award is an important indication of the significant clinical and commercial opportunity of AX09. We are extremely grateful to the NCI and our investors as we execute our development of this novel immunotherapy.”

Expression of xCT is associated with poorer outcomes in patients, with xCT being linked to tumor growth and cancer spread. Animal studies in TNBC mouse model show that AX09 significantly decreases cancer metastases and the amount of breast cancer stem cells within tumor.

“There is a desperate need for targeted therapies and combinational approaches for patients with TNBC,” said George Peoples, MD, FACS, director of the Cancer Vaccine Development Program at the http://metisfoundationusa.org/about-us/" rel="nofollow - Metis Foundation , a nonprofit that supports research relevant to military personnel. “AX09 shows promise in preclinical studies to inhibit an exploitable target and its novel mechanism of action makes AX09 a potentially powerful combination therapy to achieve durable responses for breast cancer patients.”

http://breastcancer-news.com/2018/08/13/nci-awards-2-3-million-grant-to-advance-agilvaxs-lead-candidate-ax09-to-treat-triple-negative-breast-cancer" rel="nofollow - http://breastcancer-news.com/2018/08/13/nci-awards-2-3-million-grant-to-advance-agilvaxs-lead-candidate-ax09-to-treat-triple-negative-breast-cancer



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Oct 29 2018 at 9:47pm

Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer

Background

Unresectable locally advanced or metastatic triple-negative (hormone-receptor–negative and human epidermal growth factor receptor 2 [HER2]–negative) breast cancer is an aggressive disease with poor outcomes. Nanoparticle albumin-bound (nab)–paclitaxel may enhance the anticancer activity of atezolizumab.

Methods

In this phase 3 trial, we randomly assigned (in a 1:1 ratio) patients with untreated metastatic triple-negative breast cancer to receive atezolizumab plus nab-paclitaxel or placebo plus nab-paclitaxel; patients continued the intervention until disease progression or an unacceptable level of toxic effects occurred. Stratification factors were the receipt or nonreceipt of neoadjuvant or adjuvant taxane therapy, the presence or absence of liver metastases at baseline, and programmed death ligand 1 (PD-L1) expression at baseline (positive vs. negative). The two primary end points were progression-free survival (in the intention-to-treat population and PD-L1–positive subgroup) and overall survival (tested in the intention-to-treat population; if the finding was significant, then it would be tested in the PD-L1–positive subgroup).

Results

Each group included 451 patients (median follow-up, 12.9 months). In the intention-to-treat analysis, the median progression-free survival was 7.2 months with atezolizumab plus nab-paclitaxel, as compared with 5.5 months with placebo plus nab-paclitaxel (hazard ratio for progression or death, 0.80; 95% confidence interval [CI], 0.69 to 0.92; P=0.002); among patients with PD-L1–positive tumors, the median progression-free survival was 7.5 months and 5.0 months, respectively (hazard ratio, 0.62; 95% CI, 0.49 to 0.78; P<0.001). In the intention-to-treat analysis, the median overall survival was 21.3 months with atezolizumab plus nab-paclitaxel and 17.6 months with placebo plus nab-paclitaxel (hazard ratio for death, 0.84; 95% CI, 0.69 to 1.02; P=0.08); among patients with PD-L1–positive tumors, the median overall survival was 25.0 months and 15.5 months, respectively (hazard ratio, 0.62; 95% CI, 0.45 to 0.86). No new adverse effects were identified. Adverse events that led to the discontinuation of any agent occurred in 15.9% of the patients who received atezolizumab plus nab-paclitaxel and in 8.2% of those who received placebo plus nab-paclitaxel.

Conclusions

Atezolizumab plus nab-paclitaxel prolonged progression-free survival among patients with metastatic triple-negative breast cancer in both the intention-to-treat population and the PD-L1–positive subgroup. Adverse events were consistent with the known safety profiles of each agent. (Funded by F. Hoffmann–La Roche/Genentech; IMpassion130 ClinicalTrials.gov number, http://clinicaltrials.gov/show/NCT02425891" rel="nofollow - NCT02425891 .)

https://www.nejm.org/doi/full/10.1056/NEJMoa1809615" rel="nofollow - https://www.nejm.org/doi/full/10.1056/NEJMoa1809615




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Dec 10 2018 at 7:50am

Two of these studies were highlighted at SABCS 2018:

The first is a scientifically complex study aimed at determining which patients will have the highest response rates to an immunotherapy agent known as atezolizumab, the same agent in the IMPASSION study. That trial showed patients with a marker called PD-L1 benefit from treatment with atezolizumab. This will help researchers both design future trials and personalize treatment for TNBC patients.

The second study is a phase I trial of CAR-T therapy for patients that have a specific targetable mutation, including TNBC patients. CAR-T is a technically complex form of treatment in which cells are removed from the patient, genetically re-engineered and then injected back into the patient where the goal is to stimulate an ongoing immune response to the tumor. It has been used in clinical trials with patients who have a range of leukemias, lymphomas, non small cell lung cancer and other tumors, but this is the first trial to include TNBC patients.

This is a phase I study with small numbers of patients and very early results. Only four TNBC patients were included in the data presented at SABCS, Three of them had responses to their treatment, but it is still far too soon to draw conclusions about the future of CAR-T therapy for TNBC.




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15




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