Tag Archives: breast cancer

FDA Revokes Approval of Avastin Use For Metastatic Breast Cancer; Major U.S. Ovarian Cancer Advocacy Organization Concerned

Posted on by

Today, the U.S. Food and Drug Administration (FDA) Commissioner Hamburg revoked approval of Avastin for treatment of metastatic breast cancer in the U.S. The decision does not impact Avastin’s availability for its approved uses for other cancer types in the U.S. A major U.S. ovarian cancer advocacy organization is concerned that the FDA decision will make it more difficult for ovarian cancer patients to gain access to Avastin.

FDA Revocation of Avastin Approval For Metastatic Breast Cancer

FDA Commissioner Margaret A. Hamburg, M.D., said today she is revoking the agency’s approval of the breast cancer indication for Avastin® (bevacizumab) after concluding that the drug has not been shown to be safe and effective for that use.

Avastin will still remain on the market as an approved treatment for certain types of colon, lung, kidney and brain cancer (glioblastoma multiforme).

“This was a difficult decision. FDA recognizes how hard it is for patients and their families to cope with metastatic breast cancer and how great a need there is for more effective treatments. But patients must have confidence that the drugs they take are both safe and effective for their intended use,” Dr. Hamburg said. “After reviewing the available studies it is clear that women who take Avastin for metastatic breast cancer risk potentially life-threatening side effects without proof that the use of Avastin will provide a benefit, in terms of delay in tumor growth, that would justify those risks. Nor is there evidence that use of Avastin will either help them live longer or improve their quality of life.”

Avastin’s risks include severe high blood pressure; bleeding and hemorrhaging; heart attack or heart failure; and the development of perforations in different parts of the body such as the nose, stomach, and intestines.

Today’s decision, outlined in Dr. Hamburg’s 69-page opinion, involves Avastin used in combination with the cancer drug paclitaxel (Taxol) for those patients who have not been treated with chemotherapy for their form of metastatic breast cancer known as “HER-2 negative.” This indication must now be removed from Avastin’s product labeling.

Dr. Hamburg’s decision is based on an extensive record, which includes thousands of pages submitted to a public docket, data from several clinical trials, and the record from a two-day hearing held in June, 2011.

Avastin was approved for metastatic breast cancer in February 2008 under the FDA’s accelerated approval program, which allows a drug to be approved based on data that are not sufficiently complete to permit full approval. The accelerated approval program provides earlier patient access to promising new drugs to treat serious or life-threatening conditions while confirmatory clinical trials are conducted. If the clinical trials do not justify the continued approval of the drug or a specific drug indication, the agency may revoke its approval. In this case, the accelerated approval was based on promising results from one study that suggested that the drug could provide a meaningful increase in the amount of time from when treatment is started until the tumor grows or the death of the patient.

After the accelerated approval of Avastin for breast cancer, the drug’s sponsor, Genentech (a member of the Roche Group) completed two additional clinical trials and submitted the data from those studies to the FDA. These data showed only a small effect on tumor growth without evidence that patients lived any longer or had a better quality of life compared to taking standard chemotherapy alone – not enough to outweigh the risk of taking the drug.

The FDA’s Center for Drug Evaluation and Research (CDER), which is responsible for the approval of this drug, ultimately concluded that the results of these additional studies did not justify continued approval and notified Genentech that it was proposing to withdraw approval of the indication.

Genentech did not agree with CDER’s evaluation of the data and, following the procedures set out in FDA regulations, requested a hearing on CDER’s withdrawal proposal, with a decision to be made by the FDA Commissioner. That two-day hearing, which took place June 28-29, 2011, included recommendations from the FDA’s Oncologic Drugs Advisory Committee (ODAC), voting 6-0 in favor of withdrawing approval of Avastin’s breast cancer indication. After the hearing, the public docket remained open until August 4, 2011. In an earlier meeting of the ODAC, that committee had voted 12-1 in favor of the removal of the breast cancer indication from the Avastin label.

“FDA is committed to working with sponsors to bring promising cancer drugs to market as quickly as possible using tools like accelerated approval,” Dr. Hamburg said. “I encourage Genentech to consider additional studies to identify if there are select subgroups of women suffering from breast cancer who might benefit from this drug.”

Genentech Response

In a press release issued earlier today, Genentech’s Hal Barron, M.D., chief medical officer and head, Global Product Development, stated:

“We are disappointed with the outcome. We remain committed to the many women with this incurable disease and will continue to provide help through our patient support programs to those who may be facing obstacles to receiving their treatment in the United States. Despite today’s action, we will start a new Phase III study of Avastin in combination with paclitaxel in previously untreated metastatic breast cancer and will evaluate a potential biomarker that may help identify which people might derive a more substantial benefit from Avastin.”

Genentech emphasizes the following points in its press release:

  • The FDA Commissioner revoked approval of Avastin for treatment of metastatic breast cancer in the U.S.
  • The FDA’s action concludes its review of Avastin’s use for metastatic breast cancer.
  • The FDA decision does not impact Avastin’s approved uses for other cancer types in the U.S. or other countries.
  • The FDA decision does not impact the approval of Avastin for metastatic breast cancer in more than 80 foreign countries.
  • Roche will initiate a new clinical trial of Avastin plus paclitaxel in metastatic breast cancer.
  • Genentech will issue a letter to healthcare providers and will also provide them with a letter to distribute to their patients. Both letters will be made available on Genentech’s website.
  • Patients with questions or concerns about insurance coverage, or doctors with questions about reimbursement, can call Genentech’s Access Solutions Group at (866)-4- ACCESS.
  • Doctors with questions about Avastin can call Genentech’s Medical Communications group at (800) 821-8590.
  • The FDA’s action does not impact ongoing clinical trials with Avastin in breast cancer. For more information, please call Genentech’s Trial Information Support Line at (888) 662-6728 or visit clinicaltrials.gov.

Major U.S. Ovarian Cancer Advocacy Organization Concerned About Future Impact of FDA Decision

Karen Orloff Kaplan, MSW, MPH, ScD, Chief Executive Officer, Ovarian Cancer National Alliance

Karen Orloff Kaplan, MSW, MPH, ScD, the Chief Executive Officer for the Ovarian Cancer National Alliance (OCNA), expressed concern that the removal of metastatic breast cancer from the Avastin label could negatively affect women with ovarian cancer, for whom the drug is used “off-label.”  OCNA is one of the most influential advocates for women with ovarian cancer in the United States.

Dr. Kaplan stated:

“Results from three Phase III clinical studies show that Avastin is beneficial for some women with ovarian cancer. We are deeply concerned that the Food and Drug Administration’s decision regarding metastatic breast cancer will make it difficult for women with ovarian cancer to access Avastin, and that patients could be denied insurance coverage for this treatment. The Ovarian Cancer National Alliance will continue our work to ensure that drugs that are useful and medically appropriate are available to women with this disease.”

In the FDA report accompanying her decision, Commissioner Hamburg cited a lack of evidence that Avastin improved overall survival for women with metastatic breast cancer in its decision. “Given how difficult it is to measure overall survival in ovarian cancer clinical trials, we are concerned that today’s ruling may set an unfortunate precedent,” said Dr. Kaplan.

Currently, various national cancer treatment guidelines, such as the National Comprehensive Cancer Network (NCCN) Compendium™, include Avastin as a treatment for ovarian cancer. Despite that fact, the FDA’s decision could prompt a reexamination of industry treatment guidelines by various groups, including the NCCN. The NCCN  is a nonprofit alliance which consists of 21 leading U.S. cancer centers.

Specifically, OCNA is concerned that the FDA Avastin label change, mandated by today’s FDA decision, will lead to restrictions by third party payers, including the U.S. Medicare federal insurance program, who generally reimburse for Avastin when a woman’s cancer has returned. OCNA’s concern may be warranted because Reuters reported earlier today that some healthcare insurers have already started pulling back on Avastin reimbursement coverage for breast cancer.

As of now, according to Reuters, Medicare will continue to pay for Avastin used in the treatment of breast cancer, despite  the FDA’s revocation decision. “Medicare will continue to cover Avastin,” said Don McLeod, a spokesman for the Centers for Medicare and Medicaid Services (CMS). “CMS will monitor the issue and evaluate coverage options as a result of action by the FDA but has no immediate plans to change coverage policies.” The CMS statement may mitigate concerns that patients using the drug would lose critical drug reimbursement insurance coverage in the future.

Sources:

Addtional Information:

2011 ASCO: Women with BRCA Gene Mutations Can Take Hormone-Replacement Therapy Safely After Ovary Removal

Posted on by

Women with the BRCA1 or BRCA2 gene mutations, which are linked to a very high risk of breast and ovarian cancer, can safely take hormone-replacement therapy (HRT) to mitigate menopausal symptoms after surgical removal of their ovaries, according to new research from the Perelman School of Medicine at the University of Pennsylvania

Women with the BRCA1 or BRCA2 gene mutations, which are linked to a very high risk of breast and ovarian cancer, can safely take hormone-replacement therapy (HRT) to mitigate menopausal symptoms after surgical removal of their ovaries, according to new research from the Perelman School of Medicine at the University of Pennsylvania which will be presented on Monday, June 6 during the American Society for Clinical Oncology’s annual meeting. Results of the prospective study indicated that women with BRCA mutations who had their ovaries removed and took short-term HRT had a decrease in the risk of developing breast cancer.

Research has shown that in women who carry the BRCA gene mutations, the single most powerful risk-reduction strategy is to have their ovaries surgically removed by their mid-30s or early 40s. The decrease in cancer risk from ovary removal comes at the cost of early menopause and menopausal symptoms including hot flashes, mood swings, sleep disturbances and vaginal dryness — quality-of-life issues that may cause some women to delay or avoid the procedure.

Lead study author Susan M. Domchek, M.D., Associate Professor, Divison of Hematology-Oncology & Director, Cancer Risk Evaluation Program, Abramson Cancer Center, University of Pennsylvania

“Women with BRCA1/2 mutations should have their ovaries removed following child-bearing because this is the single best intervention to improve survival,” says lead author Susan M. Domchek, M.D., an associate professor in the division of Hematology-Oncology and director of the Cancer Risk Evaluation Program at Penn’s Abramson Cancer Center. “It is unfortunate to have women choose not to have this surgery because they are worried about menopausal symptoms and are told they can’t take HRT. Our data say that is not the case — these drugs do not increase their risk of breast cancer.”

Senior author Timothy R. Rebbeck, Ph.D., associate director of population science at the Abramson Cancer Center, notes that BRCA carriers may worry — based on other studies conducted in the general population showing a link between HRT and elevated cancer risk — that taking HRT may negate the effects of the surgery on their breast cancer risk. The message he hopes doctors will now give to women is clear: “If you need it, you can take short-term HRT. It doesn’t erase the effects of the oophorectomy.”

In the current study, Domchek, Rebbeck, and colleagues followed 795 women with BRCA1 mutations and 504 women with BRCA2 mutations who have not had cancer enrolled in the PROSE consortium database who underwent prophylactic oophorectomy, divided into groups of those who took HRT and those who did not. Women who underwent prophylactic oophorectomy had a lower risk of breast cancer than those who did not, with 14 percent of the women who took HRT after surgery developing breast cancer compared to 12 percent of the women who did not take HRT after surgery. The difference was not statistically significant.

Domchek says some of the confusion about the role of HRT in cancer risk elevation comes from the fact that the risks and benefits associated with HRT depend on the population of women studied. In this group of women — who have BRCA1/2 mutations and who have had their ovaries removed while they are quite young — HRT should be discussed and considered an option for treating menopausal symptoms. “People want to make hormone replacement therapy evil, so they can say ‘Don’t do it,'” she says. “But there isn’t one simple answer. The devil is in the details of the studies.”

By contrast, Penn researchers and their collaborators in the PROSE consortium have shown definitively that oophorectomy reduces ovarian and breast cancer incidence in these women, and reduces their mortality due to those cancers. But paying attention to the role that hormone depletion following preventive oophorectomy plays in women’s future health is also important.

“We know for sure that using HRT will mitigate menopausal symptoms, and we have pretty good evidence that it will help bone health,” she says. “Women need to be aware that going into very early menopause does increase their risk of bone problems and cardiovascular problems. And even if they aren’t going to take HRT, they need to be very attentive to monitoring for those issues. But they also need to know that HRT is an option for them and to discuss it with their doctors and other caregivers.”

About Penn Medicine

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.

About the University of Pennsylvania Perelman School of Medicine

Penn’s Perelman School of Medicine is currently ranked #2 in U.S. News & World Report’s survey of research-oriented medical schools and among the top 10 schools for primary care. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.

About the University of Pennsylvania Health System

The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania — recognized as one of the nation’s top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation’s first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Sources:

ASCO 2011: Novel Multi-targeted Agent Cabozantinib (XL184) Has Significant Effect on Several Advanced Solid Tumors

Posted on by

Cabozantinib (XL184) demonstrated high rates of disease control in patients with prostate, ovarian and liver cancers. The investigators concluded that cabozantinib exhibits clinical activity in ovarian cancer patients with advanced disease, regardless of prior platinum drug status, as reflected by the high rates of response. 

ASCO Releases Studies From Upcoming Annual Meeting – Important Advances in Targeted Therapies, Screening, and Personalized Medicine

The American Society of Clinical Oncology (ASCO) today highlighted several studies in a press briefing from among more than 4,000 abstracts publicly posted online at http://www.asco.org in advance of ASCO’s 47th Annual Meeting. An additional 17 plenary, late-breaking and other major studies will be released in on-site press conferences at the Annual Meeting.

The meeting, which is expected to draw approximately 30,000 cancer specialists, will be held June 3-7, 2011, at McCormick Place in Chicago, Illinois. The theme of this year’s meeting is “Patients. Pathways. Progress.”

“This year marks the 40th anniversary of the signing of the National Cancer Act, a law that led to major new investments in cancer research. Every day in our offices, and every year at the ASCO meeting, we see the results of those investments. People with cancer are living longer, with a better quality of life, than ever before,” said George W. Sledge Jr., M.D., President of ASCO, Ballve-Lantero Professor of Oncology and professor of pathology and laboratory medicine at the Indiana University School of Medicine.

“With our growing understanding of the nature of cancer development and behavior, cancer is becoming a chronic disease that a growing number of patients can live with for many years,” said Dr. Sledge. “The studies released today are the latest examples of progress against the disease, from new personalized treatments, to new approaches to screening and prevention.”

The study results from a phase II clinical trial involving cabozantinib (XL184) were highlighted today in the ASCO press briefing, as summarized below.

Novel Multi-targeted Agent Cabozantinib (XL184) Has Significant Effect on Several Advanced Solid Tumors, and Can Shrink or Eliminate Bone Metastases 

Cabozantinib (XL184) – an oral inhibitor of MET and VEGFR2 kinases involved in the development and progression of many cancers – showed strong responses in patients with various advanced cancers in a phase II trial. The drug demonstrated particularly high rates of disease control for advanced prostate, ovarian and liver cancers, which are historically resistant to available therapies. The drug also fully or partially eliminated bone metastases in patients with breast and prostate cancers and melanoma.

Michael S. Gordon, M.D., President & Chief Executive Officer, Pinnacle Oncology Hematology.

“Cabozantinib appears to have significant effects on several treatment-resistant tumors, as well as impressive effects on bone metastases. In addition, these effects are associated with rapid improvement in pain, a reduction in opiate narcotic requirements and improvement in anemia,” said lead author Michael S. Gordon, M.D., a medical oncologist at Pinnacle Oncology Hematology located in Scottsdale, Arizona. “The implications of these results are very exciting—it is unusual to find a targeted therapy, absent of a molecular mutation in tumors, that works in bony disease and has this activity.”

To be eligible for the study, patients had to have advanced, progressive solid tumors, with or without bone metastases. Of 398 evaluable patients (of 483 enrolled in the trial), 39 percent had bone metastases at baseline. Patients received cabozantinib over 12 weeks. The trial was designed as a “discontinuation” trial, in which those who had partial responses stayed on the drug; those with stable disease were randomized to cabozantinib or placebo; and patients with progressive disease were removed from the trial. This novel type of clinical trial design more quickly evaluates the disease-stabilizing activity of growth-inhibitory agents like cabozantinib, compared to the traditional model of randomizing all patients to either the experimental arm or placebo.

Among 398 patients evaluable with all types of cancer included in the trial, the collective overall response rate was 9 percent (34 of 398). The highest disease control rates (partial response and stable disease) at week 12 were 76 percent for liver cancer (22 of 29 patients), 71 percent for prostate cancer (71 of 100 patients), and 58 percent for ovarian cancer (32 of 51 patients). [emphasis added].

Of the 51 evaluable ovarian cancer patients noted above, 28 are platinum drug resistant, 17 are platinum drug sensitive, and 6 have unknown status. The median number of systemic treatments prior to trial enrollment was 2. The overall response rate (complete response and partial response based on modified RECIST criteria) for ovarian cancer was 12/51 (24%).  Upon breakdown, the response rate was 5/28 (18%) for platinum drug resistant patients, and 5/17 (29%) for platinum drug sensitive patients. Five additional partial responses await confirmation. After a median follow-up of 4 months (range: 1 to 11 months), the median duration of response and median progression free survival have not been reached. The most common related adverse events ( ≥grade 3) among ovarian cancer patients were hand-foot syndrome (10%), diarrhea (8%) and fatigue (4%). Drug dose reductions and permanent discontinuations for adverse events occurred in 43% and 10% of the ovarian cancer patients, respectively. Based on these findings, the investigators concluded that cabozantinib exhibits clinical activity in ovarian cancer patients with advanced disease, regardless of prior platinum drug status, as reflected by the high rates of response. [emphasis added] Accordingly, randomization in the ovarian cancer cohort was halted & patients unblinded due to the observed high efficacy.

Fifty-nine of 68 patients with bone metastases (including patients with breast and prostate cancers and melanoma) experienced either partial or complete disappearance of the cancer on bone scans, often with significant pain relief and other improved cancer-related symptoms.

The reduction of bone metastases and pain relief was an unexpected finding in this study, Dr. Gordon said. Independent review by radiologists confirmed that bone metastases disappeared in the majority of patients who had bone metastases when they entered the study. The majority of these patients had castration-resistant prostate cancer (CRPC), but patients with breast cancer and melanoma also had disappearance of bone metastases. Bone metastases greatly contribute to morbidity and mortality in patients with these types of cancer, which typically spread to the bone.

Due to these results, the study has been expanded to include more CRPC patients. Similarly, the high rate of lasting responses in ovarian cancer patients led researchers to also expand the study to evaluate the drug’s effect on patients with a particularly resistant form of the disease known as platinum drug resistant/refractory ovarian cancer. [emphasis added]

This study expansion results will help determine the design of future phase III trials, which will assess whether the drug extends patients lives or has other longer-term benefits among patients with specific cancer types. At present, cabozantinib is being investigated for use as a single agent. Additional studies will evaluate the efficacy and tolerability of appropriate combinations with other agents for future indications.

For the solid tumor patients collectively, the most common grade three or above adverse events were fatigue (9 percent) and hand-foot syndrome (8 percent). Dose reductions were required in 41 percent of patients due to side effects; 12 percent were removed from the trial for adverse events.

Sources:

Resources:

Cabozantinib (XL184) Clinical Trials:

Related Libby’s H*O*P*E*™ Postings:

Outside-the-Box: The Rogosin Institute Is Fighting Cancer With Cancer Cells In Clinical Trials

Posted on by

Researchers at the Rogosin Institute are using cancer “macrobeads” to fight cancer.  Cancer cells in the beads secrete proteins which researchers believe could signal a patient’s cancer to stop growing, shrink or even die. The treatment is currently being tested in human clinical trials.

Two groundbreaking preclinical studies demonstrate for the first time that encapsulated mouse kidney cancer cells inhibit the growth of freely-growing cancer cells of the same or different type in a laboratory dish and in tumor-bearing animals. These findings support the hypothesis that cancer cells entrapped in seaweed-based gel, called “macrobeads,” send biological feedback or signals to freely-growing tumors outside the macrobead to slow or stop their growth. Both studies (cited below) are published in the on-line January 24, 2011 issue of Cancer Research, a publication of the American Association For Cancer Research.

Barry H. Smith, M.D., Ph.D., Director, The Rogosin Institute; Professor, Clinical Surgery, Weill Cornell Medical College

The Rogosin Institute, an independent not-for-profit treatment and research center associated with New York-Presbyterian Hospital and Weill Cornell Medical College, developed the cell encapsulation technology that facilitated production of the macrobead and applied this technology in conducting preclinical studies. The research team was headed by Barry H. Smith, M.D., Ph.D.,  the Director of The Rogosin Institute, Professor of Clinical Surgery at the Weill Cornell Medical College, and lead author of the studies. Findings in the studies to date are consistent with the hypothesis that when macrobeads are implanted in a host, the encapsulated cells are isolated from the host’s immune system but continue to maintain their functionality.

In addition to the standard preclinical in vivo and in vitro experiments, a clinical veterinary study was conducted in cats and dogs suffering from various spontaneous (non-induced) cancers. More than 40 animals were treated with the macrobead technology. Consistent results, measured both in terms of tumor response and animal well-being, occurred with prostate, liver and breast cancer, as well as lymphoma. Additional research revealed that regardless of the animal specie or type of cancer cell that was encapsulated, the macrobead technology inhibited cancer growth across all species and cancer types tested.  The results have included slowed tumor growth or, in some cases, necrosis and elimination of tumors and the restoration of a normal animal lifespan.

Cancer macrobead therapy has proceeded to human clinical testing. A Phase 1 trial in more than 30 patients evaluated the safety of macrobeads implanted in the abdominal cavity as a biological treatment of end-stage, treatment-resistant, epithelial-derived cancer. Based on the safety profile data, Phase 2 efficacy trials are in progress in patients with colorectal cancer, pancreatic cancer and prostate cancer. The Phase 1 trial remains open to a range of epithelial-derived cancers, including ovarian.  To date, the Rogosin Institute research team has not found evidence to indicate that placing mouse tumors in humans or other animal species causes harm or side-effects.

Scientists are testing whether macrobeads containing cancer cells can be implanted into patients and communicate with the patient’s tumor to stop growing, shrink or die.

Step 1:  Small beads are made from a seaweed-derived sugar called agarose and mixed with 150,000 mouse kidney cancer cells, and a second layer of agarose is added, encapsulating the cancer cells.

Step 2:  Within 3-to-10 days, 99% of the kidney cancer cells die.  The remaining cells have traits similar to cancer stem cells.

Step 3:  The stem cells begin to recolonize the bead.  The colonies increase in sufficient numbers within a few weeks to reach a stable state.

Step 4:  The beads begin to release proteins —  chemical signals reflecting that the beads have sufficient numbers of cells for growth regulators to kick in.

Step 5: Several hundred beads (depending on patient’s weight) are implanted in the abdominal cavity in a laparoscopic surgical procedure.  The cancer cells are trapped in the beads; preventing their circulation elsewhere in the body and protecting them from attack by the body’s immune system.

Step 6: In animal studies, researchers believe some proteins released from the beads reached tumors elsewhere in the body and tricked them into sensing that other tumor cells are nearby.

Step 7:  As a result, researchers believe tumors in some animals stopped growing, shrank or died.  The hypothesis is being tested in people with cancer.

Howard Parnes, M.D., Chief, Prostate & Urologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute

“This is a completely novel way of thinking about cancer biology,” says Howard L. Parnes, a researcher in the Division of  Cancer Prevention at the National Cancer Institute who is familiar with the work but was not involved with it. “We talk about thinking outside the box. It’s hard to think of a better example.” “They demonstrate a remarkable proof of principle that tumor cells from one animal can be manipulated to produce factors that can inhibit the growth of cancers in other animals,” Dr. Parnes says. “This suggests that these cancer inhibitory factors have been conserved over millions of years of evolution.”

“Macrobead therapy holds promise as a new option in cancer treatment because it makes use of normal biological mechanisms and avoids the toxicities associated with traditional chemotherapy,” said Dr. Barry Smith. “The results of our research show that this approach is not specific to tumor type or species so that, for example, mouse cells can be used to treat several different human tumors and human cells can be used to treat several different animal tumors.”

“Because cancer and other diseases are their own biological systems, we believe that the future of effective disease treatment must likewise be biological and system-based,” said Stuart Subotnick, CEO of Metromedia Bio-Science LLC. “Many of the existing therapies are narrow, targeted approaches that fail to treat diseases comprehensively. In contrast, our unique macrobead technology delivers an integrated cell system that alters disease processes and utilizes the body’s natural defense mechanisms. The goal is to repair the body and not merely treat the symptoms.”

It is well-known that proof of anti-tumor activity in treating animals does not represent guaranteed effectiveness in humans. But, assuming the macrobead therapy proves ultimately effective in humans, it would represent a novel approach to treating cancer and challenge existing scientific dogmas.

The cancer macrobead therapy described above is backed by Metromedia Company, a privately held telecommunications company which was run by billionaire John Kluge until his recent death. The Metromedia Biosciences unit has invested $50 million into the research.  If the treatment proves successful in humans, a large part of the revenue generated will be contributed to Mr. Kluge’s charitable foundation.

About Metromedia Bio-Science LLC

Metromedia Bio-Science LLC, in conjunction with The Rogosin Institute, utilizes the novel cell encapsulation technology to conduct research into the treatment of various diseases, including cancer and diabetes, and the evaluation of disease therapies. Metromedia Bio-Science LLC is an affiliate of Metromedia Company, a diversified partnership founded by the late John W. Kluge and Stuart Subotnick.

About The Rogosin Institute

The Rogosin Institute is an independent not-for-profit treatment and research center associated with New York-Presbyterian Hospital (NYPH) and Weill Cornell Medical College. It is one of the nation’s leading research and treatment centers for kidney disease, providing services from early stage disease to those requiring dialysis and transplantation. It also has programs in diabetes, hypertension and lipid disorders. The Institute’s cancer research program, featuring the macrobeads, began in 1995. The Rogosin Institute is unique in its combination of the best in clinical care with research into new and better ways to prevent and treat disease.

References:

Clinical Trials:

PARP Inhibitor MK-4827 Shows Anti-Tumor Activity in First Human Clinical Study

Posted on by

MK-4827, a new drug that targets proteins responsible for helping cancer cells repair their damaged DNA, has shown promising anti-tumor activity in its first human clinical trial.

MK-4827, a new drug that targets proteins responsible for helping cancer cells repair their damaged DNA, has shown promising anti-tumour activity in its first human clinical trial. Some patients with a range of solid tumors, many of whom had been treated unsuccessfully for their cancer with other therapies, have seen their tumors shrink or stabilize for periods of between 46 days to more than a year. The research will be presented today (Thursday) at the 22nd EORTC–NCI–AACR [1] Symposium on Molecular Targets and Cancer Therapeutics, which is being held in Berlin, Germany.

PARP is a key signaling enzyme involved in triggering the repair of single-strand DNA damage. PARP inhibition has been demonstrated to selectively kill tumor cells lacking components of the homologous recombination (HR) DNA repair pathway while sparing normal cells. Known defects in HR repair include the well-characterized hereditary BRCA1 and BRCA2 mutations in breast and ovarian cancer, as well as nonhereditary BRCA mutations. (Photo Credit: AstraZeneca Oncology)

Laboratory studies of the drug, MK-4827, have shown that it inhibits proteins called PARP1 and PARP2 (poly(ADP)-ribose polymerase). PARP is involved in a number of cellular processes and one of its important functions is to assist in the repair of single-strand breaks in DNA. Notably, if one single-strand DNA break is replicated (replication occurs before cell division), then it results in a double-strand break.  By inhibiting the action of PARP, double-strand breaks occur, which in turn, lead to cell death. Tumors that are caused by a mutation in the BRCA1 or BRCA2 genes are susceptible to cell death through PARP inhibition because correctly functioning BRCA genes assist in repairing double-strand DNA breaks via a process called homologous-recombination-dependent DNA repair, whereas mutated versions are unable to perform this role. Normal cells do not replicate as often as cancer cells and they still have homologous repair operating; this enables them to survive the inhibition of PARP and makes PARP a good target for anti-cancer therapy.

In a Phase I trial [2] conducted at the H. Lee Moffitt Cancer Center (Tampa Florida, USA), University of Wisconsin-Madison (Madison, USA) and the Royal Marsden Hospital (London, UK), MK-4827 was given to 59 patients (46 women, 13 men) with a range of solid tumors such as non-small cell lung cancer (NSCLC), prostate cancer, sarcoma, melanoma and breast and ovarian cancers. Some patients had cancers caused by mutations in the BRCA1/2 genes, such as breast and ovarian cancer, but others had cancers that had arisen sporadically.

Robert M. Wenham, M.D., MS, FACOG, Clinical Director, Gynecologic Oncology, Department of Women's Oncology, H. Lee Moffitt Cancer Center

The drug was given in pill form once a day, and the researchers found that the maximum tolerated dose was 300 mg per day. Dr. Robert Wenham, Clinical Director for Gynecologic Oncology in the Department of Women’s Oncology at the Moffitt Cancer Center, who is presenting data on behalf of the participating investigators, said: “MK-4827 is generally well tolerated, with the main dose-limiting toxicity being thrombocytopenia – an abnormal decrease in the number of platelets in the circulatory blood. The most common side effects are mild nausea, vomiting, anorexia and fatigue.”

The researchers saw anti-tumor responses in both sporadic (non-inherited) and BRCA1/2 mutation-associated cancers [emphasis added]. Ten patients with breast and ovarian cancers had partial responses, with progression-free survival between 51-445 days, and seven of these patients are still responding to treatment. Four patients (two with ovarian cancer and two with NSCLC) had stable disease for between 130-353 days.

Dr. Wenham said: “Most patients in the trial had exhausted standard therapies and those who responded to this drug have benefited. Several patients have been receiving treatment for more than a year. The responses mean that MK-4827 is working as hoped and justify additional studies. Just how well MK-4827 works compared to other treatments is the goal of the next set of studies.”

He gave a possible explanation as to why patients with cancers that were not caused by BRCA1 or BRCA 2 gene mutations also responded to the PARP inhibition. “BRCA is a tumor suppressor gene that assists in repairing double stranded DNA breaks. In BRCA-mutation related cancers, loss of both copies of the gene results in a non-functional protein and thus BRCA deficiency. Because BRCA works with other proteins, BRCA-pathway related deficiency can be seen in the absence of two mutated copies of the BRCA genes. This may explain why responses have been reported for this class of drugs in non-BRCA mutant cancers.”

Dr. Wenham and his colleagues are recruiting more patients for additional studies and an expansion of the existing trial. “We want to understand what types of cancers will respond best to treatment with MK-4827,” he said. “Cohorts are currently open for patients with ovarian cancer, patients without germ-line BRCA mutations, and prostate cancer patients. Cohorts will open soon for patients with T-cell prolymphocytic leukemia, endometrial cancer, breast cancer and colorectal cancer. MK-4827 is also being studied in combination with conventional chemotherapy drugs.”

Sources:

Additional Information:

Related Information:

References:

[1] EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].

[2] This study was funded by Merck & Co., Inc. MK-4827 is owned by Merck & Co., Inc.

Researchers Identify “Missing Link” Underlying DNA Repair & Platinum Drug Resistance

Posted on by

Researchers have discovered an enzyme crucial to a type of DNA repair that also causes resistance to a class of cancer drugs most commonly used against ovarian cancer.

Scientists from The University of Texas MD Anderson Cancer Center and the Life Sciences Institute of Zhejiang University in China report the discovery of the enzyme and its role in repairing DNA damage called “cross-linking” in the Science Express advance online publication of Science.

Junjie Chen, Ph.D., Professor and Chair, Department of Experimental Radiation Oncology, University of Texas M.D. Anderson Cancer Center

“This pathway that repairs cross-linking damage is a common factor in a variety of cancers, including breast cancer and especially in ovarian cancer. If the pathway is active, it undoes the therapeutic effect of cisplatin and similar therapies,” said co-corresponding author Junjie Chen, Ph.D., professor and chair of MD Anderson’s Department of Experimental Radiation Oncology.

The platinum-based chemotherapies such as cisplatin, carboplatin and oxaliplatin work by causing DNA cross-linking in cancer cells, which blocks their ability to divide and leads to cell death. Cross-linking occurs when one of the two strands of DNA in a cell branches out and links to the other strand.

Cisplatin and similar drugs are often initially effective against ovarian cancer, Chen said, but over time the disease becomes resistant and progresses.

Scientists have known that the protein complex known as FANCI–FANCD2 responds to DNA damage and repairs cross-linking, but the details of how the complex works have been unknown. “The breakthrough in this research is that we finally found an enzyme involved in the repair process,” Chen said.

The enzyme, which they named FAN1, appears to be a nuclease, which is capable of slicing through strands of DNA.

In a series of experiments, Chen and colleagues demonstrated how the protein complex summons FAN1, connects with the enzyme and moves it to the site of DNA cross-linking. They also showed that FAN1 cleaves branched DNA but leaves the normal, separate double-stranded DNA alone. Mutant versions of FAN1 were unable to slice branched DNA.

Like a lock and key

The researchers also demonstrated that FAN1 cannot get at DNA damage without being taken there by the FANCI-FANCD2 protein complex, which detects and moves to the damaged site. The complex recruits the FAN1 enzyme by acquiring a single ubiquitin molecule. FAN1 connects with the complex by binding to the ubiquitin site.

“It’s like a lock and key system, once they fit, FAN1 is recruited,” Chen said.

Analyzing the activity of this repair pathway could guide treatment for cancer patients, Chen said, with the platinum-based therapies used when the cross-linking repair mechanism is less active.

Scientists had shown previously that DNA repair was much less efficient when FANCI and FANCD2 lack the single ubiquitin. DNA response and damage-repair proteins can be recruited to damage sites by the proteins’ ubiquitin-binding domains. The team first identified a protein that had both a ubiquitin-binding domain and a known nuclease domain. When they treated cells with mitomycin C, which promotes DNA cross-linking, that protein, then known as KIAA1018, gathered at damage sites. This led them to the functional experiments that established its role in DNA repair.

They renamed the protein FAN1, short for Fanconi anemia-associated nuclease 1. The FANCI-FANCD2 complex is ubiquitinated by an Fanconi anemia (FA) core complex containing eight FA proteins. These genes and proteins were discovered during research of FA, a rare disease caused by mutations in 13 fanc genes that is characterized by congenital malformations, bone marrow failure, cancer and hypersensitivity to DNA cross-linking agents.

Chen said the FANCI-FANCD2 pathway also is associated with the BRCA1 and BRCA2 pathways, which are involved in homologous recombination repair. Scientists know that homologous recombination repair is also required for the repair of DNA cross-links, but the exact details remain to be resolved, Chen said. Mutations to BRCA1 and BRCA2 are known to raise a woman’s risk for ovarian and breast cancers and are found in about 5-10 percent of women with either disease.

Co-authors with Chen are co-first author Gargi Ghosal, Ph.D., and Jingsong Yuan, Ph.D., also of Experimental Radiation Oncology at MD Anderson; and co-corresponding author Jun Huang, Ph.D., co-first author Ting Liu, Ph.D., of the Life Sciences Institute of Zhejiang University in Hangzhou, China.

This research was funded by a grant from the U.S. National Institutes of Health and the Startup Fund at Zhejiang University.

Sources:

ESMO Clinical Practice Guidelines Regarding BRCA Gene Mutations, Ovarian Cancer & Supportive Cancer Care

Posted on by

The European Society for Medical Oncology (ESMO) is the leading European professional organization committed to advancing the specialty of medical oncology, and promoting a multidisciplinary approach to cancer treatment and care. …  The ESMO Clinical Practice Guidelines include coverage of  (i) BRCA gene mutations in breast and ovarian cancer, (ii) gynecologic tumors, and (iii) supportive cancer care …

The European Society for Medical Oncology (ESMO) is the leading European professional organization committed to advancing the specialty of medical oncology, and promoting a multidisciplinary approach to cancer treatment and care.  Since its founding in 1975 as a non-profit organization, ESMO’s mission is to support oncology professionals in providing people with cancer the most effective treatments available at the highest quality of care.

Formerly known as the ESMO Clinical Recommendations, the ESMO Clinical Practice Guidelines (CPG) are intended to provide users with a set of requirements for the highest standard of care for cancer patients. The ESMO CPG represent vital, evidence-based information including the incidence of the malignancy, diagnostic criteria, staging of disease and risk assessment, treatment plans and follow-up.

A growing number of the new guidelines were developed using large, multidisciplinary writing groups, ensuring optimal input from the oncology profession and better geographic representation.

For example, two revised guidelines address the prevention of chemotherapy- and radiotherapy–induced nausea and vomiting, developed as a result of the 3rd Perugia Consensus Conference organized by the Multinational Association of Supportive Care in Cancer (MASCC) and ESMO.

The new guidelines published this month and available online represent the first stage of a process that will include recommendations for more than 55 different clinical situations, covering almost all tumor types as well as various other topics including the therapeutic use of growth factors.

The ESMO Clinical Practice Guidelines include coverage of  (i) BRCA gene mutations in breast and ovarian cancer, (ii) gynecologic tumors, and (iii) supportive cancer care, as provided below.

Breast Cancer

Gynecologic Tumors

Supportive Care

Sources:

Researchers Identify A New Breast & Ovarian Cancer Susceptibility Gene

Posted on by

German researchers identify a new breast and ovarian cancer susceptibility gene known as “RAD51C.”  The risk for breast cancer in women with the RAD51C mutation is 60 to 80 percent, while the risk for ovarian cancer is 20 to 40 percent.

The discovery 15 years ago that the genes BRCA1 and BRCA2 confer high risks for breast and ovarian cancer was a breakthrough for cancer prediction and therapy, especially for familial cases.  Now the research group of Prof. Alfons Meindl (Klinikum rechts der Isar of the Technische Universitaet Muenchen), in collaboration with other groups from Germany, the U.K., and the U.S., can identify another gene that increases susceptibility to breast and ovarian cancer. Their results have been published online in Nature Genetics. The identification of such high risk-conferring genes is a prerequisite for offering women tailored early recognition programs and more individualized therapies.

The gene newly identified as causing breast and ovarian cancer in familial cases is designated RAD51C. It is, like BRCA1 and BRCA2, essential for DNA repair within cells. Mutations in the gene can therefore cause either breast or ovarian cancer. In index cases from 1,100 German families with gynecological malignancies, six mutations within the RAD51C gene were found exclusively in 480 pedigrees [i.e., family trees] with occurrence of breast and ovarian cancer. The six RAD51C mutations were not found in 620 pedigrees with breast cancer only, or in 2,912 healthy German controls.  The risk for breast cancer in women with mutation of RAD51C is 60 to 80 percent, while the risk for ovarian cancer is 20 to 40 percent. As the cancers in such families were diagnosed significantly earlier than in women who developed sporadic breast or ovarian cancer, experts might also call the newly identified gene BRCA3.

“These results reinforce our assumption that various rare gene mutations contribute to hereditary breast and ovarian cancer. The now known genes that predispose women to breast and/or ovarian cancer only explain 60 percent of the high-risk families,” says TUM Professor Alfons Meindl, Klinikum rechts der Isar, but novel technologies allow the rapid identification of other such rarely mutated disease-causing genes.

“We are also optimistic that in the future the individual breast cancer risks for the majority of women can be determined. These risk predictions will allow the offering of tailored prevention and small meshed early recognition programs. Risk-aligned prevention will become a new clinical area,” explains Prof. Dr. Rita Schmutzler of the University Hospital of Cologne, one of the other main authors of the article.

About Technische Universitaet Muenchen

Technische Universitaet Muenchen (TUM) is one of Germany’s leading universities. It has roughly 420 professors, 7,500 academic and non-academic staff (including those at the university hospital “Rechts der Isar”), and 24,000 students. It focuses on the engineering sciences, natural sciences, life sciences, medicine, and economic sciences. After winning numerous awards, it was selected as an “Elite University” in 2006 by the Science Council (Wissenschaftsrat) and the German Research Foundation (DFG). The university’s global network includes an outpost in Singapore. TUM is dedicated to the ideal of a top-level research based entrepreneurial university. http://www.tum.de

About Klinikum rechts der Isar, Munich, Germany

The Klinikum rechts der Isar (on the right hand side of the river Isar) serves its patients with a highly skilled team of dedicated doctors, nurses, research scientists, and technical assistants. The Klinikum rechts der Isar is a university hospital of the Technische Universitaet Muenchen.  With a workforce of over 4,000 personnel, the university hospital is a renowned center for the care of the sick, for medical research, and for the teaching of medicine. The Klinikum rechts der Isar is composed of more than 30 separate clinics and departments treating some 45,000 in-house patients and 170,000 out-patients yearly. With more than 1,000 beds, the hospital covers the entire spectrum of modern medicine with state-of-the-art efficiency. Through the close cooperation between health care and research, the latest advances in medical techniques can be quickly integrated into patient treatment procedures.

Sources:

Libby’s H*O*P*E* to Present At NOCC 6th Annual Women’s Health Expo (REJUVENATE Finding Balance)

Posted on by

On March 20, 2010, the National Ovarian Cancer Coalition (Maryland Chapter) will hold its 6th Annual Women’s Health Expo entitled, REJUVENATE Finding Balance (NOCC Rejuvenate), at the Sheraton Annapolis Hotel. … On behalf of Libby’s H*O*P*E*™, I will conduct a seminar as part of Session II entitled, A Patient Advocate’s Perspective on the Importance of Ovarian Cancer Awareness and Related On-line Resources.

On March 20, 2010, the National Ovarian Cancer Coalition (Maryland Chapter) will hold its 6th Annual Women’s Health Expo entitled, REJUVENATE Finding Balance (NOCC Rejuvenate), at the Sheraton Annapolis Hotel. NOCC Rejuvenate is sponsored by the National Breast & Ovarian Cancer Connection and Cancer Treatment Centers of America.  Additional funding was also provided through a grant from the Maryland Attorney General Settlement.

NOCC Rejuvenate is designed to appeal to all women who want to rejuvenate their mind, body and spirit. The event is divided into three sessions. Each session offers seven to eight different seminars for attendees. The seminars address a variety of topics including make-up and skin care, going green, photography, plastic surgery, decorating, fashion, finance, retirement solutions, nutrition, fitness, and holistic approaches to wellness. A list of all event seminars is provided below.

Informative seminars about ovarian and breast cancer are offered as part of each session. Knowing the signs and symptoms of ovarian cancer, the screening guidelines for breast cancer, and the basics about hereditary breast and ovarian cancer, could save your life or the life of someone you love.  On behalf of Libby’s H*O*P*E*™, I will conduct a seminar as part of Session II entitled, A Patient Advocate’s Perspective on the Importance of Ovarian Cancer Awareness and Related On-line Resources.  My presentation will address the genesis of the Libby’s H*O*P*E*™ website; highlight critical ovarian cancer awareness information; summarize available online ovarian cancer and cancer-related resources; describe stories of hope involving ovarian cancer survivors and their families; and explain how each individual can make a difference in the fight against ovarian cancer.

NOCC Rejuvenate also targets cancer survivors. The devastating effects of these diseases can rob women of hope and peace. This event will offer an opportunity for survivors to reinvent their self-image and gain more knowledge, offering a sense of hope and a chance to connect with other survivors.

An exhibitor’s area will be offered at the event. This area will include informational tables as well as vendor tables that have been specifically chosen to meet the overarching vision of the event. At the completion of the three event sessions, a nutritious lunch will be served while information is provided on the signs and symptoms of ovarian and breast cancer.

NOCC 6th Annual Women's Health Expo

What:  National Ovarian Cancer Coalition 6th Annual Women’s Health Expo entitled, REJUVENTE Finding Balance (click here to view event brochure, including mail-in registration)

When: Saturday, March 20, 2010 (8:00 A.M. – 3:00 P.M.)

Where: Sheraton Annapolis Hotel, 173 Jennifer Road, Annapolis, Maryland 21401 (driving instructions).

Register: To register online click here.

Contact: Nancy Long (NOCC Maryland Chapter Co-President) at 443-433-2597, or email (click here).

Keynote Speaker:  Yarrow, The Energy Whisperer

Session I Presentations (9:30 A.M. – 10:30 A.M.)

  • Treating Cancer By Alternative Medicine
  • The Survivors’ Connection
  • The Skinny on Fat – Cancer Prevention Naturally
  • Interior Design in Difficult Times – Cost Saving Design Solutions
  • Relaxation & Healing
  • Identifying & Solving the Challenges of Baby Boomer Women
  • Cancer and The Healing Power of Forgiveness
  • Belly Dancing

Session II Presentations (10:45-11:45)

  • Dr. Zandra Cheng, Breast Surgeon at Anne Arundel Medical Center
  • Hereditary Syndromes That Include Ovarian and Breast Cancers
  • Facial & Body Rejuvenation
  • A Patient Advocate’s Perspective On the Importance of Ovarian Cancer Awareness & Related On-line Resources (Paul Cacciatore, Founder, Libby’s H*O*P*E*™)
  • Designing Green Interiors
  • Creating Better Images with the Camera You Own
  • Some Expert Fashion Tips
  • Yoga:  A Balanced Life
  • Relaxation & Healing

Session III Presentations (12:00 P.M. – 1:00 P.M.)

  • New Advances in Ovarian Cancer (William McGuire, M.D., Medical Director of The Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital)
  • What is My Daughter’s Chance of Getting My Cancer?
  • Planning for your Retirement Lifestyle:  The New Retirement
  • Super Health Begins with Super-food Nutrition
  • Around the World to Your Backyard
  • Balancing Your Life Wheel
  • Get Fit & Healthy with the Simple Rules of the Big 3
  • Relaxation & Healing

About the National Ovarian Cancer Coalition

The mission of the NOCC is to raise awareness and increase education about ovarian cancer. NOCC is committed to improving the survival rate and quality of life for women with ovarian cancer. Through national programs and local Chapter initiatives, the NOCC’s goal is to make more people aware of the early symptoms of ovarian cancer. In addition, the NOCC provides information to assist the newly diagnosed patient, to provide hope to survivors, and to support caregivers. NOCC programs are possible only with the help of its volunteers; committed men and women dedicated to the mission of the NOCC in communities across the country.  For more information go to http://www.ovarian.org/.

About the National Breast & Ovarian Cancer Connection

The mission of the NBOCC is to raise awareness and educate the general public about the link between breast and ovarian cancer. The organization is dedicated to teaching all women about their inherent risks and how to improve their chances of survival through early detection and research developments.  For more information go to http://www.nbocc.org/.

Women Often Opt to Surgically Remove Their Breasts, Ovaries to Reduce Cancer Risk

Posted on by

Many women at high risk for breast or ovarian cancer are choosing to undergo surgery as a precautionary measure to decrease their cancer risk, according to a report in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

PHILADELPHIA – Many women at high risk for breast or ovarian cancer are choosing to undergo surgery as a precautionary measure to decrease their cancer risk, according to a report in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

Gareth

Dr. Gareth Evans is an international authority on cancer genetics. Dr. Evans is the Chairman of the National Institute For Health & Clinical Excellence (NICE) familial breast cancer group; Chairman, Cancer Genetics Group & Council Member, British Society of Human Genetics; Consultant, Genesis Prevention Center, Univ. Hospital of South Manchester NHS Trust; Professor, Univ. of Manchester, UK

“Women have their breasts or ovaries removed based on their risk.

Claudine_2009_July_(photo_credit_Phil_Humnicky,_Georgetown)

Dr. Claudine Isaacs is an Associate Professor of Medicine, Director of the Familial Cancer Registry Shared Resource, Director of the Clinical Breast Cancer Program, and the Co-Medical Director of the Fisher Center for Familial Cancer Research at the Lombardi Comprehensive Cancer Center, Georgetown Univ., Washington, D.C. (photo credit: Phil Humnicky, Georgetown Univ.)

It does not always happen immediately after counseling or a genetic test result and can take more than seven years for patients to decide to go forward with surgery,” said lead researcher D. Gareth Evans, M.D. Evans is a consultant in clinical genetics at the Genesis Prevention Center, University Hospital of South Manchester NHS Trust and a professor at the University of Manchester, United Kingdom.

Evans and colleagues assessed the increase in risk-reduction surgery among women with breast cancer and evaluated the impact of cancer risk, timing and age.

Rate of increase was measured among 211 women with known unaffected BRCA1 or BRCA2 mutation carriers. BRCA1 and BRCA2 are hereditary gene mutations that indicate an increased risk for developing breast cancer. Additionally, more than 3,500 women at greater than 25 percent lifetime risk of breast cancer without mutations also had a documented increase in risk-reduction surgery.

Women who had a biopsy after undergoing risk evaluation were twice as likely to choose a risk-reducing mastectomy. Forty percent of the women who were mutation carriers underwent bilateral risk-reducing mastectomy; 45 percent had bilateral risk-reducing salpingo-oophorectomy (surgical removal of ovaries). These surgeries are widely used by carriers of BRCA1 and BRCA2 gene mutations to reduce the risk for breast and ovarian cancer.

Evaluated by gene type, bilateral risk-reducing salpingo-oophorectomy was more common in women who were BRCA1 gene carriers – 52 percent had the surgery compared with 28 percent of the women who were BRCA2 gene carriers.

“We found that older women were much less likely to have a mastectomy, but were more likely to have their ovaries removed,” said Evans.

Most of the women, specifically those aged 35 to 45 years, opted for surgery within the first two years after the genetic mutation test, but some did not make a decision until seven years later.

“This is a very interesting study. It fleshes out some of what we know about adoption of risk reduction strategies in high-risk women who have participated in a very comprehensive and well thought-out genetic counseling, testing and management program,” said Claudine Isaacs, M.D., an associate professor of medicine and co-director of the Fisher Center for Familial Cancer Research, Lombardi Comprehensive Cancer Center at Georgetown University.

BRCA1 and BRCA2 mutation carriers have a very high lifetime risk of cancer, and for BRCA1 carriers there are unfortunately no clearly proven non-surgical prevention strategies, according to Isaacs. These women face a 50 to 85 percent lifetime risk of breast cancer, and mastectomy is currently the most effective prevention method available.

The findings confirm the expectations that when a woman has a biopsy, even if benign, most are more likely to opt for risk-reduction surgery.

“Screening should be conducted at a place with expertise in an effort to minimize false-positive results, which often lead to biopsy. This will minimize the anxiety that comes along with such a diagnosis. Patients should consult with an expert in advance and stay in contact with them to see how the science may be changing over time,” she advised. “This is an ongoing conversation that needs to be addressed and individualized for each patient.”

Likewise, Evans suggested that additional studies are needed to help evaluate the communication efforts and methods between doctors and/or counselors and women at risk for breast cancer. Questions to be raised should include how is the communication method occurring, are the doctors sympathetic and is there an ongoing dialogue?

“Careful risk counseling does appear to influence women’s decision for surgery although the effect is not immediate,” the researchers wrote.

References:

Stand Up To Cancer Funded Research Dream Team Takes Aim At Women’s Cancers

Posted on by

Stand Up To Cancer (SU2C), the Entertainment Industry Foundation’s charitable initiative supporting groundbreaking research aimed at getting new cancer treatments to patients in an accelerated timeframe, has reached a significant milestone, awarding the first round of three-year grants — that total $73.6 million — to five multi-disciplinary, multi-institutional research Dream Teams. … Each Dream Team’s project, funded for three years pending satisfactory achievement of stated milestones, is “translational” in nature, geared toward moving science from “bench to bedside” where it can benefit patients as quickly as possible. …

A Dream Team of leading cancer researchers will accelerate development of drugs to attack a mutated [PI3K] molecular pathway that fuels endometrial, breast and ovarian cancers, funded by a three-year $15 million grant awarded today by [SU2C] … Genetic aberrations in the network, known as the PI3K pathway, are found in half of all breast cancer patients, 60 percent of all cases of endometrial cancer and 20 percent of ovarian cancer patients. Other cancers that include a mutationally activated PI3K pathway include melanoma, colon and prostate cancers, brain tumors, and leukemia.

Continue reading →

UPCI Launches Clinical Trial for Patients with Hereditary Breast and Ovarian Cancers

Posted on by

“The University of Pittsburgh Cancer Institute (UPCI) will be the primary site for a clinical trial of ABT-888, a drug previously proven in combination treatments to improve chemotherapy’s effectiveness by lowering cancer cells’ resistance to treatment. This trial will, for the first time, examine ABT-888 as a single agent for patients with cancers related to BRCA 1 or 2 genetic mutations, which predispose patients to breast and ovarian cancers. …”

Continue reading →

Women of Diverse Ethnic Ancestry Have Similar Risk of Carrying BRCA Mutations as Those With Western European Ancestry

Posted on by

” …The study, performed by researchers at Philadelphia’s Fox Chase Cancer Center and Myriad Genetics, Inc., analyzed the prevalence of BRCA1/BRCA2 gene mutations in patients of different ethnicities at risk for hereditary breast and ovarian cancer. The study included test results of 46,276 women during the ten-year period from 1996 to 2006. Study subjects encompassed a broad, diverse ethnic group, including individuals of European, Latin American, African, Asian and Native American ancestries. … Results of the study showed that BRCA disease-causing mutations were identified in 5,780 women tested (12.5%) across all ethnic populations. Importantly, the study demonstrated that individuals of African and Latin American ancestry had as great a risk in having BRCA mutations as women with western European ancestry, when controlled for the level of personal and family history of breast and ovarian cancer. …”

“New Study Published in CANCER Supports Use of BRACAnalysis Testing Across Broad Ethnic Populations

Women of Asian, African and Latin American Ancestry Had Similar Risk of Carrying BRCA Mutations as Those With Western European Ancestry

SALT LAKE CITY, UT, Apr 30, 2009 (MARKET WIRE via COMTEX News Network) — Myriad Genetics, Inc. (NASDAQ: MYGN) announced today that an article entitled ‘BRCA1 and BRCA2 Mutations in Women of Different Ethnicities Undergoing Testing for Hereditary Breast-Ovarian Cancer‘ will appear in the May 15, 2009 issue of the journal CANCER.  The study demonstrates that BRACAnalysis(R) testing of at-risk women across diverse ethnicities helps identify individuals who may benefit from improved surveillance, medical and surgical strategies to reduce their hereditary cancer risks.

critchfield

Gregory C. Critchfield, M.D., M.S., President, Myriad Genetic Laboratories

‘This study, the largest of its kind, shows convincingly that strong family or personal history of breast or ovarian cancer is associated with a high prevalence of BRCA mutations — irrespective of one’s ethnic heritage,’ stated Gregory C. Critchfield, M.D., M.S., President of Myriad Genetic Laboratories.

The association between ethnicity and the risk of BRCA1 or BRCA2 mutations has not been well understood in women of non-European ancestry. This study provides important information for women of Asian, African, Latin American and Native American ancestry that may impact breast cancer [and ovarian cancer] prevention and treatment efforts among women in these populations. The study, performed by researchers at Philadelphia’s Fox Chase Cancer Center and Myriad Genetics, Inc., analyzed the prevalence of BRCA1/BRCA2 gene mutations in patients of different ethnicities at risk for hereditary breast and ovarian cancer. The study included test results of 46,276 women during the ten-year period from 1996 to 2006. Study subjects encompassed a broad, diverse ethnic group, including individuals of European, Latin American, African, Asian and Native American ancestries. To date, this work represents the largest group of patients tested for BRCA mutations reported in the literature. All testing was performed at Myriad Genetics, Inc.

Results of the study showed that BRCA disease-causing mutations were identified in 5,780 women tested (12.5%) across all ethnic populations. Importantly, the study demonstrated that individuals of African and Latin American ancestry had as great a risk in having BRCA mutations as women with western European ancestry, when controlled for the level of personal and family history of breast and ovarian cancer.

Professional medical society guidelines, such as the American Society of Clinical Oncologists (ASCO), the Society of Gynecologic Oncologists (SGO), and the American College of Obstetricians and Gynecologists (ACOG), articulate risk factors for BRCA gene mutations, which include, among others, breast cancer occurring before age 50, personal or family history of ovarian cancer at any age, personal or family history of male breast cancer, Ashkenazi Jewish ancestry with breast cancer at any age, or the presence of a known BRCA mutation in the family.

About BRACAnalysis(R)

BRACAnalysis(R) is a comprehensive analysis of the BRCA1 and BRCA2 genes for assessing a woman’s risk for breast and ovarian cancer. A woman who tests positive with the BRACAnalysis(R) test has, on average, an 82% lifetime risk of developing breast cancer during her lifetime and a 44% risk of developing ovarian cancer. BRACAnalysis(R) provides important information that the Company believes will help the patient and her physician make better informed lifestyle, surveillance, preventive medication and treatment decisions. As published in the Journal of the National Cancer Institute, researchers have shown that pre-symptomatic individuals who have a high risk of developing breast cancer can reduce their risk by approximately 50% with appropriate preventive therapies. Additionally, as published in the New England Journal of Medicine, researchers have shown that pre-symptomatic individuals who carry gene mutations can lower their risk of developing ovarian cancer by approximately 60% with appropriate preventive therapies.

For more information about BRACAnalysis(R), please call 1-800-4-MYRIAD, or visit www.myriadtests.com.

About Myriad Genetics

Myriad Genetics, Inc. is a leading healthcare company focused on the development and marketing of novel molecular diagnostic and therapeutic products. Myriad’s news and other information are available on the Company’s Web site at www.myriad.com.

Myriad, the Myriad logo, BRACAnalysis, Colaris, Colaris AP, Melaris, TheraGuide, Prezeon, OnDose, Azixa and Vivecon are trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and foreign countries. MYGN-G”

Sources: 

Related Information:  CLICK HERE to review all Libby’s H*O*P*E*™ postings relating to BRCA gene mutations.

PhRMA Report Shows Record Number of Development Drugs to Treat Cancer; 63 Ovarian Cancer & 203 Solid Tumor Drugs Listed

Posted on by

“Responding to President Obama’s call for ‘a cure for cancer in our time,’ the Pharmaceutical Research and Manufacturers of America (PhRMA) delivered a new report today on medicines in the research pipeline for cancer. The report shows that America’s pharmaceutical research and biotechnology companies are testing a record 861 new cancer medicines and vaccines. The medicines listed in the report are being tested in human clinical trials or are awaiting approval by the U.S. Food and Drug Administration. [Libby’s H*O*P*E*™ : 63 Ovarian Cancer Drugs & 203 Solid Tumor Drugs are listed in the 2009 PhRMA report (pp. 51 – 55)]. …”

“New Report Shows Record Number of Medicines In Development to Treat Leading Causes of Cancer

phrmalogoDenver, CO (April 1, 2009) – Responding to President Obama’s call for ‘a cure for cancer in our time,’ the Pharmaceutical Research and Manufacturers of America (PhRMA) delivered a new report today on medicines in the research pipeline for cancer. The report shows that America’s pharmaceutical research and biotechnology companies are testing a record 861 new cancer medicines and vaccines. The medicines listed in the report are being tested in human clinical trials or are awaiting approval by the U.S. Food and Drug Administration. [Libby’s H*O*P*E*™ Note: 63 Ovarian Cancer Drugs & 203 Solid Tumor Drugs are listed in the 2009 PhRMA report (pp. 51-55)].

Nationwide, cancer is the second leading cause of death, affecting more than 10 million Americans, according to the National Cancer Institute. This year, more than half a million Americans are expected to die of cancer-more than 1,500 a day. In Colorado, the lifetime risk of cancer is 1 in 2 for males and 2 in 5 for females. The most commonly diagnosed cancer in the state is breast cancer, followed by prostate and lung cancer.

‘We released this report in Denver because of Colorado’s growing role in developing cancer medicines,’ said PhRMA Senior Vice President Ken Johnson, who unveiled the report at the State Capitol Building.

‘Oncology is one of Colorado’s core research competencies, so the President’s call to cure cancer resonates powerfully in our state,’ said Colorado Lt. Governor Barbara O’Brien. ‘We are proud that the cancer medicines now in the research pipeline in Colorado are contributing substantially to the incredible progress made in the last five years by biopharmaceutical companies in developing new and more effective cancer treatments. The nation must continue its strong commitment to the cutting-edge pharmaceutical research that will enable cancer patients to live longer, healthier, and more productive lives.’

billytauzin

Billy Tauzin, President and Chief Executive Officer, The Pharmaceutical Research and Manufacturers of America (PhRMA). PhRMA's mission is to conduct effective advocacy for public policies that encourage discovery of important new medicines for patients by pharmaceutical & biotechnology research companies.

‘I am one of those patients who was diagnosed with cancer and was given a new treatment that brought me from the brink of death back to life,’ says PhRMA President and CEO Billy Tauzin. ‘The men and women working for America’s pharmaceutical research companies are committed to developing new cancer medicines that, one day, could eradicate cancer all together.’

Cancer medicines being developed include 122 for lung cancer, the leading cause of cancer death in the United States; 107 for breast cancer, which is expected to strike more than 180,000 American women this year; 70 for colorectal cancer, which is the third most common cancer in both men and women; and 103 for prostate cancer, which this year is expected to kill 28,000 American men. Additional medicines target brain cancer, kidney cancer, ovarian cancer, pancreatic cancer, skin cancer, and others.

The medicines represent many cutting-edge approaches, including a drug that delivers a synthetic version of a substance derived from scorpions directly to brain tumor cells; a number of cancer vaccines; medicines that target and kill specific cancer cells; and treatments that activate the patient’s general immune system to destroy cancer.

‘Researchers are making exciting progress in the search for new cures and treatments for cancer. But these efforts are wasted if the medicines we develop aren’t accessible to patients who need them,’ said Johnson.

Help is available to patients in need through the Partnership for Prescription Assistance (PPA), a program sponsored by America’s pharmaceutical research companies. To date, the PPA has helped more than 5.7 million patients nationwide, including more than 72,000 people in Colorado. Since its launch in April 2005, the PPA bus tour has visited all 50 states and more than 2,500 cities to educate people about patient assistance programs.

The “Help is Here Express” is staffed by trained specialists able to quickly help uninsured and financially struggling patients access information on more than 475 patient assistance programs, including nearly 200 programs offered by pharmaceutical companies. When the “Help is Here Express” moves on, patients can visit PPA’s easy-to-use Web site (www.pparx.org) or call the toll-free phone number (1-888-4PPA-NOW).

Click here to read Medicines in Development for Cancer 2009. [Adobe Reader PDF Doc.]

Read the backgrounder fact sheet here.

______________________________________________________

Pharmaceutical Research & Manufacturers of America

The Pharmaceutical Research and Manufacturers of America (PhRMA) represents the country’s leading pharmaceutical research and biotechnology companies, which are devoted to inventing medicines that allow patients to live longer, healthier, and more productive lives. PhRMA companies are leading the way in the search for new cures. PhRMA members alone invested an estimated $50.3 billion in 2008 in discovering and developing new medicines. Industry-wide research and investment reached a record $65.2 billion in 2008.

PhRMA Internet Address: www.phrma.org

For information on stories of hope and survival, visit: http://sharingmiracles.com/

PhRMA en Español: www.nuestraphrma.org

For information on how innovative medicines save lives, visit: www.innovation.org

For information on the Partnership for Prescription Assistance, visit: www.pparx.org

For information on the danger of imported drugs, visit: www.buysafedrugs.info”

Source:  New Report Shows Record Number of Medicines In Development to Treat Leading Causes of Cancer, Press Release, Pharmaceutical Research and Manufacturers of America, April 1, 2009.

Two Studies Address Risk Reduction & Screening For BRCA 1/2 Gene Mutation Carriers

Posted on by

“Prophylactic salpingo-oophorectomy – removal of the ovaries and fallopian tubes–reduces the relative risk of breast cancer by approximately 50 percent and the risk of ovarian and fallopian tube cancer by approximately 80 percent in women who carry a mutation in the BRCA1 or BRCA2 gene, researchers report in the January 13 online issue of the Journal of the National Cancer Institute …. Women at high risk of ovarian cancer due to a genetic predisposition may opt for either surveillance or prophylactic bilateral salpingo-oophorectomy (pBSO).  Main objective of our study was to determine the effectiveness of ovarian cancer screening in women with a BRCA1/2 mutation.  At this time,’ Dr. de Bock and colleagues advise, “prophylactic bilateral salpingo-oophorectomy from age 35-40 for BRCA1 carriers and from age 40-45 for BRCA2 carriers is the only effective strategy, as it reduces the risk of ovarian cancer by 96% and may also protect against breast cancer with a risk reduction up to 53% when performed in premenopausal women.’ They add, ‘For women who still want to opt for screening, a more effective screening strategy needs to be designed.'”

Meta-analysis Confirms Value of Risk-Reducing Salpingo-Oophorectomy
for Women with BRCA Mutations

“Prophylactic salpingo-oophorectomy – removal of the ovaries and fallopian tubes–reduces the relative risk of breast cancer by approximately 50 percent and the risk of ovarian and fallopian tube cancer by approximately 80 percent in women who carry a mutation in the BRCA1 or BRCA2 gene, researchers report in the January 13 online issue of the Journal of the National Cancer Institute .  Previous studies have shown substantial reduction in the risks of breast and ovarian or fallopian tube cancers in BRCA1/2 mutation carriers following salpingo-oophorectomy. However, the magnitude of the benefit has been unclear.

To establish a more reliable estimate of the magnitude of the benefit, Timothy Rebbeck, Ph.D., of the University of Pennsylvania School of Medicine in Philadelphia, and colleagues analyzed the pooled results of 10 published studies.  They found that risk-reducing salpingo-oophorectomy was associated with a 79 percent relative reduction in ovarian and fallopian tube cancer risk and a 51 percent relative reduction in breast cancer risk in women who carried mutations in BRCA1 or BRCA2 . When the researchers analyzed the effect of the prophylactic surgery on BRCA1 and BRCA2 mutation carriers separately, they found a similar benefit for the two groups in terms of breast cancer risk, with a 53 percent risk reduction for each group. The groups were too small to be examined independently for gynecologic cancer risk. ‘In conclusion, the summary risk reduction estimates presented here confirm that BRCA1/2 mutation carriers who have been treated with [risk-reducing salpingo-oophorectomy] have a substantially reduced risk of both breast and ovarian cancer,’ the authors write. ‘However, residual cancer risk remains after surgery. Therefore, additional cancer risk reduction and screening strategies are required to maximally reduce cancer incidence and mortality in this high-risk population.’

In an accompanying editorial, Mark H. Greene, M.D., and Phuong L. Mai, M.D., of the National Cancer Institute in Bethesda, Md., commend Rebbeck and colleagues ‘ effort and review the steps the study authors took to develop the most precise estimates of risk reduction following prophylactic salpingo-oophorectomy. The results ‘should benefit women who are trying to decide whether or not to undergo [risk-reducing salpingo-oophorectomy],’ the editorialists write. ‘We urge providers of cancer genetics counseling services to adopt the summary risk estimates developed by Rebbeck et al. as those most currently reliable when counseling BRCA mutation carriers.’

Contacts:
Article: Holly Auer, Holly.auer@uphs.upenn.edu ; 215-349-5659
Editorial: NCI Press Officers, ncipressofficers@mail.nih.gov ; 301-496-6641

Citations:
Article: Rebbeck T, et al. Meta-analysis of Risk Reduction Estimates Associated with Risk Reducing Salpingo-
Oophorectomy in BRCA1 or BRCA2 Mutation Carriers. J Natl Cancer Inst 2009;101: 80 – 87 .
Editorial: Greene M and Mai PL. What Have We Learned from Risk-Reducing Salpingo-oophorectomy? J Natl
Cancer Inst 2009;101: 7 – 71 .”

Quoted Source:  MEMO TO THE MEDIA -Meta-analysis Confirms Value of Risk-Reducing Salpingo-oophorectomy for Women with BRCA Mutations, JNCI  2009 101(2):69 (online Jan. 13, 2009).

Time to stop ovarian cancer screening in BRCA1/2 mutation carriers?

“Women at high risk of ovarian cancer due to a genetic predisposition may opt for either surveillance or prophylactic bilateral salpingo-oophorectomy (pBSO).  Main objective of our study was to determine the effectiveness of ovarian cancer screening in women with a BRCA1/2 mutation.

We evaluated 241 consecutive women with a BRCA1 or BRCA2 mutation who were enrolled in the surveillance program for hereditary ovarian cancer from September 1995 until May 2006 at the University Medical Center Groningen (UMCG), The Netherlands. The ovarian cancer screening included annual pelvic examination, transvaginal ultrasound (TVU) and serum CA125 measurement. To evaluate the effectiveness of screening in diagnosing (early stage) ovarian cancer sensitivity, specificity, positive and negative predictive values (PPV and NPV) of pelvic examination, TVU and CA125 were calculated.

Three ovarian cancers were detected during the surveillance period; 1 prevalent cancer, 1 interval cancer and 1 screen-detected cancer, all in an advanced stage (FIGO stage IIIc).  A PPV of 20% was achieved for pelvic examination, 33% for TVU and 6% for CA125 estimation alone. The NPV were 99.4% for pelvic examination, 99.5% for TVU and 99.4% for CA125. All detected ovarian cancers were in an advanced stage, and sensitivities and positive predictive values of the screening modalities are low. Restricting the analyses to incident contacts that contained all 3 screening modalities did not substantially change the outcomes. Annual gynecological screening of women with a BRCA1/2 mutation to prevent advanced stage ovarian cancer is not effective.”

Citation:  Time to stop ovarian cancer screening in BRCA1/2 mutation carriers?, van der Velde NM, Mourits, MJ,  Arts HJ, et. al.; Int J Cancer 2008;Vol 124: Issue 4: 919-923.

Comment: “At this time,’ Dr. de Bock and colleagues advise, “prophylactic bilateral salpingo-oophorectomy from age 35-40 for BRCA1 carriers and from age 40-45 for BRCA2 carriers is the only effective strategy, as it reduces the risk of ovarian cancer by 96% and may also protect against breast cancer with a risk reduction up to 53% when performed in premenopausal women.’ They add, ‘For women who still want to opt for screening, a more effective screening strategy needs to be designed.'” [Source:  Annual Screening for Ovarian Cancer in BRCA1/2 Carriers Deemed Ineffective, News Article, Cancerpage.com, Feb. 23, 2009.]