FDA begins process to remove breast cancer indication from Avastin label

The U.S. Food and Drug Administration announced today (December 16) that the agency is recommending removing the breast cancer indication from the label for Avastin (bevacizumab) because the drug has not been shown to be safe and effective for that use.

The agency is making this recommendation after reviewing the results of four clinical studies of Avastin in women with breast cancer and determining that the data indicate that the drug does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression to outweigh the significant risk to patients. These risks include severe high blood pressure; bleeding and hemorrhage; the development of perforations (or “holes”) in the body, including in the nose, stomach, and intestines; and heart attack or heart failure.

In July 2010, after reviewing all available data an independent advisory committee, composed primarily of oncologists, voted 12-1 to remove the breast cancer indication from Avastin’s label.

“After careful review of the clinical data, we are recommending that the breast cancer indication for Avastin be removed based on evidence from four independent studies,” Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “Subsequent studies failed to confirm the benefit observed in the original trial. None of the studies demonstrated that patients receiving Avastin lived longer and patients receiving Avastin experienced a significant increase in serious side effects. The limited effects of Avastin combined with the significant risks led us to this difficult decision. The results of these studies are disappointing. We encourage the company to conduct additional research to identify if there may be select groups of patients who might benefit from this drug.”

Removing the breast cancer indication from the Avastin label will be a process. This is the first step. The drug itself is not being removed from the market and today’s action will not have any immediate impact on its use in treating breast cancer. Today’s action will not affect the approvals for colon, kidney, brain, and lung cancers.

Oncologists currently treating patients with Avastin for metastatic breast cancer should use their medical judgment when deciding whether a patient should continue treatment with the drug or consider other therapeutic options.

The agency has informed Genentech, Avastin’s manufacturer, of its proposal to withdraw marketing approval of the drug for breast cancer. Genentech has not agreed to remove the breast cancer indication voluntarily, so the agency has issued a Notice of Opportunity for a Hearing, which permits Genentech to request a public hearing if it wishes to contest the agency’s determination. The company has 15 days to request a hearing; if it does not do so, the hearing will be waived, and FDA will begin proceedings to remove the breast cancer indication.

Avastin, in combination with chemotherapy (paclitaxel), was approved in February 2008 under the FDA’s accelerated approval program, based on the results of a clinical trial known as “E2100,” which evaluated the drug in patients who had not received chemotherapy for their metastatic HER2-negative breast cancer. Under the accelerated approval program, a drug may be approved based on clinical data that suggest the drug has a meaningful clinical benefit, with more information being needed to confirm this. The program provides earlier patient access to promising new drugs to treat serious or life-threatening conditions while confirmatory clinical trials are conducted.

After the accelerated approval of Avastin for breast cancer, Genentech completed additional clinical trials and submitted the data from those studies to the FDA. These data showed only a small effect on “progression-free survival” without evidence of an improvement in overall survival or a clinical benefit to patients sufficient to outweigh the risks. The small increase in “progression-free survival” reflects a small, temporary effect in slowing tumor growth.

Avastin has also been associated with several other serious and potentially life-threatening side effects including the risk of stroke, wound healing complications, organ damage or failure; and the development of a neurological condition called reversible posterior leukoencephalopathy syndrome (RPLS), characterized by high blood pressure, headaches, confusion, seizures, and vision loss from swelling of the brain.

On the basis of all available data relating to the use of Avastin to treat metastatic breast cancer, the agency has determined that the risks of the drug outweigh the benefits for this use.

FDA is open to working with Genentech on any proposals to conduct additional studies of Avastin in patients with metastatic breast cancer designed to identify a population of patients in which the drug’s benefits exceed the risks.

------
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG
www.FayetteFrontPage.com
Twitter: @FayetteFP

FDA Approves New Treatment Option for Late-Stage Breast Cancer

/PRNewswire/ -- The U.S. Food and Drug Administration today approved Halaven (eribulin mesylate) to treat patients with metastatic breast cancer who have received at least two prior chemotherapy regimens for late-stage disease.

Breast cancer is the second leading cause of cancer related death among women, according to the National Cancer Institute. This year, an estimated 207,090 women will be diagnosed with breast cancer, while 39,840 women will die from the disease.

Halaven is a synthetic form of a chemotherapeutically active compound derived from the sea sponge Halichondria okadai. This injectable therapy is a microtubule inhibitor, believed to work by inhibiting cancer cell growth. Before receiving Halaven, patients should have received prior anthracycline- and taxane-based chemotherapy for early or late-stage breast cancer.

Halaven's safety and effectiveness were established in a single study in 762 women with metastatic breast cancer who had received at least two prior chemotherapy regimens for late-stage disease. Patients were randomly assigned to receive treatment with either Halaven or a different single agent therapy chosen by their oncologist.

The study was designed to measure the length of time from when this treatment started until a patient's death (overall survival). The median overall survival for patients receiving Halaven was 13.1 months compared with 10.6 months for those who received a single agent therapy.

"There are limited treatment options for women with aggressive forms of late-stage breast cancer who have already received other therapies," said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research. "Halaven shows a clear survival benefit and is an important new option for women."

The most common side effects reported by women treated with Halaven include a decrease in infection-fighting white blood cells (neutropenia), anemia, a decrease in the number of white blood cells (leukopenia), hair loss (alopecia), fatigue, nausea, weakness (asthenia), nerve damage (peripheral neuropathy), and constipation.

Other FDA-approved therapies used to treat late-stage, refractory breast cancer include Xeloda (capecitabine) for patients with breast cancer resistant to paclitaxel and anthracycline-containing chemotherapy; Ixempra (ixabepilone) for patients with late- stage disease after failure of an anthracycline, taxane and Xeloda; and Ixempra plus Xeloda for patients with late-stage disease after failure of anthracycline- and taxane-based chemotherapy.

Halaven is marketed by Woodcliff Lakes, N.J. -based Eisai Inc.

-----
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG
www.FayetteFrontPage.com
Twitter: @FayetteFP

Mammography availability linked to breast cancer mortality rate

More women die of breast cancer in areas where mammography centers are few and far between, according to research by a Medical College of Georgia radiology resident.

Breast cancer mortality rates ranged from 34.1 per 100,000 women in counties with no mammography facilities to 27.5 in those with at least one, said Dr. Kandace Klein, a fourth-year radiology resident.

Drs. Klein and James Rawson, Warren professor and chair of the Department of Diagnostic, Therapeutic and Interventional Radiology, presented their findings at the recent annual conference of the Radiology Society of North America. Dr. Klein also received the society’s Trainee Research Prize for the project.

Researchers used mapping and statistical software to determine the relationship between the number of sites in a specific geographical area and the number of breast cancer deaths. While this phase of the research did not account for variables such as race, education or socioeconomic status, a noticeable pattern emerged.

“The number of sites within a county is related to the population,” Dr. Klein said. “Increasing access to a facility correlates with a decrease in mortality.”

Researchers could not account for mobile mammography units and any transfer cases, such as when a patient went to another county to receive mammography services. The next phase of the project will analyze other factors that could affect breast cancer mortality rates, she said.

Dr. Klein, a graduate of the Texas College of Osteopathic Medicine, will complete her residency this spring and begin an MCG fellowship in body imaging.

By Jennifer Hilliard
MCG

-----
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page
Follow us on Twitter: @GAFrontPage

Secretary Pulls Cover Off the Work of Government Medical Panel

/PRNewswire/ -- U.S. Health and Human Services Secretary Kathleen Sebelius is to be commended for publicly stating the government panel opposing mammograms is "an outside independent panel of doctors and scientists who ... do not set federal policy and ... don't determine what services are covered by the federal government."

ZERO - The Project to End Prostate Cancer has long criticized this panel, known as the U.S. Preventive Services Task Force (USPSTF), for being out of touch due to its steadfast opposition to recognize the need for prostate cancer early detection as an important men's health issue.

Now, this panel is criticizing the need for mammograms.

Based on its advisory opinions on both breast cancer and prostate cancer, USPSTF has created much confusion among millions of women and men who are now being told that preventive health measures should not be followed as a means to detect cancer.

"Prostate cancer is essentially 'the forgotten illness' as far as this outside government panel is concerned," said ZERO's CEO Quentin "Skip" Lockwood.

"We're pleased the Secretary is speaking up in defense of a woman's right to continue receiving mammograms to protect her health," he said.

"We now call upon the Secretary to address the importance of prostate cancer early detection for men as well, since USPSTF has turned its back on this issue."

Advocates for mammograms and prostate cancer testing also question the membership of the USPSTF panel due to the glaring omission of medical specialists relating to women's and men's health in the fields of radiology, oncology and urology, for example.

Earlier today, the American College of Radiology called upon the Secretary to ensure the panel included "experts from the areas on which they will be advising lawmakers and submit their recommendations for comment and review," as is done with Medicare guidelines.

Ironically, the supporting data used by USPSTF does indicate mammography screening reduces breast cancer deaths by 15 percent annually. For prostate cancer, USPSTF references an ongoing screening study where early detection (using the PSA test) has so far reduced deaths by 20 percent.

"It's obvious this government panel has some explaining to do and hopefully, with prodding from the Secretary, we will get some answers to explain their contradictory position," Lockwood said.

Similarities between breast and prostate cancer data in the U.S. are striking. Each is the most frequently diagnosed noncutaneous cancer and the second leading cause of cancer death for their gender. In 2009, new cases of each cancer were at about 194,000. One in six men is struck with prostate cancer annually; for breast cancer, it's one in eight women.

-----
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page

Sebelius Statement on New Breast Cancer Recommendations

HHS Secretary Kathleen Sebelius issued the following statement today on new breast cancer screening recommendations from the U.S. Preventive Services Task Force:

"There is no question that the U.S. Preventive Services Task Force Recommendations have caused a great deal of confusion and worry among women and their families across this country. I want to address that confusion head on. The U.S. Preventive Task Force is an outside
independent panel of doctors and scientists who make recommendations. They do not set federal policy and they don't determine what services are covered by the federal government.

"There has been debate in this country for years about the age at which routine screening mammograms should begin, and how often they should be given. The Task Force has presented some new evidence for consideration but our policies remain unchanged. Indeed, I would be very surprised if any private insurance company changed its mammography coverage decisions
as a result of this action.

"What is clear is that there is a great need for more evidence, more research and more scientific innovation to help women prevent, detect, and fight breast cancer, the second leading cause of cancer deaths among women.

"My message to women is simple. Mammograms have always been an important life-saving tool in the fight against breast cancer and they still are today. Keep doing what you have been doing for years - talk to your doctor about your individual history, ask questions, and make the
decision that is right for you."

-----
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page

New Coalition Created to Help Breast Cancer Survivors Gain Access to Products Designed to Improve Their Quality of Life

A national coalition of patient advocates, physicians, business groups, non-profit organizations and other stakeholders, has been created to help breast cancer survivors gain better access to high quality prostheses and related post-surgical items. Known as Because We CARE (Breast Cancer Survivor Coalition for the Advancement, Reform and Equity), the coalition, a non-profit organization (www.becausewecarecoalition.com) launched this week with the support of U.S. Congressman Phil Gingrey, MD (R-GA). Gingrey spent more than 25 years in a successful OB-GYN practice in Georgia and is an advocate of women's health issues.

"It is time for members of congress to recognize that current Medicare formulas have created a system that deprives many breast cancer survivors and others in need of products and services that can help them move on with their lives. The coalition is a great way to draw attention to this issue," said Gingrey.

Organizations supporting the coalition include Amoena USA Corporation and the National Coalition for Cancer Survivorship. In addition to national support, other organizations include Willie's Specialty Shop in Orange, CA, Late Bloomers in San Mateo, CA, New Day's Dawn in Santee, CA, The Profile Shop in PA, Special Lady Boutique in KY, A Place For Her in FL, Touching You in AL, Enhance by Linda Reib in CA, Barbara Graves Intimate Fashion in AR, and The Pink Petal in South Hadley, MA.

"We joined forces to create this Coalition because we all are extremely dedicated to providing breast cancer survivors with better access to products that will give them the quality of life they deserve," said Bonnie Marshall, patient advocate and breast cancer survivor. "We also understand the issues affecting women's healthcare coverage and the importance of gaining access to breast prostheses, symmetry shapers and other post surgical items. We want to raise awareness of the issues facing women affected by breast cancer and work toward removing barriers that inhibit them from maintaining their dignity and improving their quality of life."

After having surgery to treat breast cancer, many survivors struggle to regain the quality of life they experienced before their diagnosis. Health care research has found that the sooner women can feel whole again, and regain their sense of femininity, the sooner they will be able to move on with their lives.

High quality, doctor-prescribed external breast prostheses can assist a high percentage of the 2.5 million breast cancer survivors living in the United States in achieving this goal. However, due to the formula created by the Centers for Medicare and Medicaid Services (CMS), coverage of breast prostheses differs from state to state. Regardless of health care coverage -- commercial or Medicare -- these disparities effectively limit choice and may deprive women of the best available breast forms and related supplies.

For additional information on Because We Care members and legislative outreach, visit www.becausewecarecoalition.com.

-----
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page

Blue Cross and Blue Shield of Georgia Expands Breast Cancer Care Program

PRNewswire/ -- As October, Breast Cancer Awareness Month, draws to a close, Blue Cross and Blue Shield of Georgia (BCBSGa) understands that it is truly a year-round effort, and is taking additional steps to further improve breast cancer care and awareness for its members. The BCBSGa Breast Cancer Care Program, designed for patients with breast cancer and their physicians, has helped more than 16,000 Georgians navigate through the emotional hardship experienced when undergoing treatment/care for breast cancer.

The goals of this quality improvement program are:

-- To improve breast cancer care and to provide awareness and targeted interventions that will promote informed decision making through meaningful discussions between the patient and the health care team

-- To improve appropriate treatment selections consistent with accepted standards of care and best practice guidelines

-- To provide frontline support to patients with breast cancer.

"It is a wonderful surprise, and a great feeling, to know my insurance company cares," noted Jenifer Hinkemeyer, BCBSGa member. "The program includes useful resources that helped me understand and cope with my diagnosis and treatment."

"When we developed the program, we formed two advisory panels, one of physicians and one of survivors and support organization leaders, to ensure we would provide the most beneficial program for all audiences," said Sandra White, M.D., medical director, BCBSGa. "We identified the most salient messages for each audience in order to ensure the information provided would be well-received and informative. Materials were developed and the program rollout began. We are thrilled with the response thus far and are continuing to expand materials and outreach."

With feedback from the advisory panels, BCBSGa created four new collateral pieces. The materials address the various needs of breast cancer patients at different stages of their cancer journey. "These pieces are designed to provide comprehensive information to support informed decision-making, delivered in a simple, clearly stated manner -- suitable for a diverse audience," said Dr. White.

The program materials include:

-- BCBSGa Resource List - offers support and additional helpful resources to breast cancer patients and their caregivers.

-- BCBSGa Patient Educational Book - contains information on many topics related to breast cancer. This booklet is designed to help patients with breast cancer understand and cope with their disease.

-- BCBSGa Patient Checklist of Questions to Ask the Doctor -- suggests questions for the patient to ask their doctors at each stage of treatment, helping patients arrive at the treatment decisions they are most comfortable with.

-- BCBSGa General Treatment Guidelines for Breast Cancer -- provides information on diagnosis staging of breast cancer and the related treatment decisions or options. This quick reference tool is designed for physicians who are not oncology specialists, to discuss breast cancer treatment options with their patients in general terms.

"We have received a great deal of positive feedback from our members and medical providers. We understand what a difficult and confusing time it can be when being diagnosed with or diagnosing breast cancer," noted Dr. White. "Our goal is to ease the confusion and increase communications between the caregiver and the patient. We believe we are succeeding through this program."

The program reaches all BCBSGa products -- HMO/POS, PPO, and Indemnity. To date, educational materials have been distributed to more than 16,000 patients nationally, and more than 5,200 physicians at more than 7,800 office locations throughout Georgia. The program is expected to reach more than 3,500 patients annually.

In addition to individual requests for the materials, BCBSGa has collaborated with community and clinical organizations to distribute the program materials to their constituents, providing nearly 20,000 component pieces. Among others, the National Black Leadership Initiative on Cancer (NBLIC) partners and the Breast Health Connection of Georgia are including the BCBSGa tools within their community-based distribution networks throughout Georgia (reaching more than 600 breast cancer advocates annually). In addition, the Winship Cancer Institute at Emory University has selected the BCBSGa Patient Education Book as part of their patient support program and the staff of the Grady Health Clinic at the Atlanta Hartsfield-Jackson International Airport is making program materials available for use in their health clinic activities.

BCBSGa is currently involved in a research project that will help BCBSGa identify additional educational needs and address possible disparities. BCBSGa is also researching how to achieve an effective transition of care from the cancer specialist back to the primary care physician for long-term follow-up with breast cancer survivors.

In addition to direct distribution, program materials are available for viewing and download on the BCBSGa Web site, www.bcbsga.com. For more information, please contact Nancy A. Rodriguez at 404-848-2334 or nancy.rodriguez@bcbsga.com.

-----
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page

Breast cancer Cells Recycle to Escape Death by Hormonal Therapy

Many breast cancer cells facing potentially lethal antiestrogen therapy recycle to survive, researchers say.

About 70 percent of breast cancer cells have receptors for the hormone estrogen, which acts as a nutrient and stimulates their growth. Patients typically get an antiestrogen such as tamoxifen for five years to try to starve them to death, says Dr. Patricia V. Schoenlein, cancer researcher in the Medical College of Georgia Schools of Medicine and Graduate Studies.

"About 50 to 60 percent of these women really benefit from hormonal therapy," says Dr. Schoenlein. Why others don't has been asked for at least two decades.

One reason may be breast cancer cells switch into a survival mode that normal cells also use when faced with starvation, according to research published in the September issue of Molecular Cancer Therapeutics. Dr. Schoenlein also is reporting on the research during the 2nd World Conference on Magic Bullets (Ehrlich II) Oct. 3-5 in Nürenberg, Germany.

It's called macroautophagy – autophagy means "self eating" – and within a week, breast cancer cells can reorganize component parts, degrade non-essentials and live in this state until antiestrogen therapy is stopped or the cells mutate and resume proliferation in the presence of tamoxifen. "It's like taking your foot off of the gas pedal of your car," says Dr. Schoenlein, corresponding author on the study. "The cancer cell is in idle, unable to grow or replicate. But the cell is smart enough to use component parts generated by macroautophagy for the most necessary things required for survival." She notes that macroautophagy can't be maintained indefinitely; cells can actually self-digest. "This is a time-buying strategy."

Chemotherapeutic drugs are more direct killers but also kill healthy cells and can be tolerated by patients only for relatively short periods. Antiestrogen therapy is more specific, targeting breast cancer cells that express estrogen receptors.

In the laboratory, 20-25 percent of breast cancer cells died when Dr. Schoenlein and colleagues gave antiestrogen continuously over time – similar to how patients get it. More typically, the cells expressed increasing levels of macroautophagy and survived. "They don't grow, but they survive the therapy. They will grow if you take away the therapy." Adding a macroautophagy inhibitor promoted robust cell death.

"We believe targeting the autophagosome function will significantly improve the efficacy of hormonal treatment for estrogen-positive breast cancer," says the researcher. She recently received a three-year, $1.1 million National Cancer Institute grant to pursue that strategy.

She'll now look for ways to block macroautophagy in an animal model, including using chloroquine, a drug used to treat malaria. "We know patients can take it with few side effects," she says. If it works in animals, the drug, in combination with an antiestrogen, could move relatively quickly into human testing.

During autophagy, the internal pH for the recycling center of the reorganized cell gets acidic and chloroquine increases pH. "If you add this particular inhibitor of the recycling center, you alter the pH and block its ability to do what it is supposed to do," says Dr. Schoenlein.

A University of Pennsylvania team led by Dr. Craig Thompson reported in 2007 in The Journal of Clinical Investigation that chloroquine increased death of suicide-resistant lymphoma cells being treated with chemotherapy. Dr. Schoenlein will give chloroquine along with an antiestrogen and measure cell death.

"Most cancers probably use autophagy as a survival mechanism. You can either block the autophagosome with your therapy or you can make the cell eat itself to the point of no return and the cell self-destructs. You have to push it either way," she says. Although there are no known compounds in clinical use to induce self-destruction by autophagy, there is some evidence arsenic trioxide, a compound used in China to treat some aggressive cancers, prompts cancer cells to die from self digestion, she says. That and other compounds will no doubt be studied further, she says.

Dr. Schoenlein believes breast cancer survival during macroautophagy requires high activity of the tumor suppressor protein Rb and low levels of the lipid ceramide. Ceramide is vital but causes cell death at high levels. MCG researcher Erhard Bieberich and colleague Dr. Brian G. Condie at the University of Georgia showed in 2003 that high levels of ceramide kill cells that are unnecessary to the developing brain. The new studies will further explore the roles of Rb and ceramide in breast cancer survival during macroautophagy and determine if chloroquine can change their balance.

By Toni Baker
Medical College of Georgia

-----
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page

Sarah Cannon Research Institute Presents New Findings in Breast Cancer Treatment

BUSINESS WIRE --Sarah Cannon Research Institute (SCRI) investigators have found that “smart bomb” therapies are effective in treating breast cancer patients while minimizing side effects.

Howard A. Burris III, M.D., SCRI’s chief medical officer, presented interim Phase II clinical trial results of a drug named Trastuzumab-DM1 (T-DM1), a novel antibody drug conjugate, on September 5th at the American Society of Clinical Oncology’s Breast Cancer Symposium in Washington, D.C.

T-DM1 is built from the widely used antibody Herceptin. T-DM1 combines Herceptin’s HER2 blocking activity with a targeted intracellular delivery of a potent anti-microtubule agent directly into HER2-positive breast cancer cells. In 20 percent of breast cancer cases, the patient’s cancer has too much of the HER2 protein, which makes the cancer cells grow and divide more quickly. T-DM1 is designed to focus delivery of treatment to HER2-positive cancer cells and limit delivery to surrounding healthy tissue.

Dr. Burris and his team were the first oncologists to treat patients with T-DM1 in December 2006. Minimal toxicities have been observed in the trial to date.

“Physicians call it a ‘smart bomb’ because it’s designed to hit the target cancerous cells with minimal collateral damage to its neighboring non-cancerous cells,” Dr. Burris said.

Thirty-one patients with HER2-positive metastatic breast cancer whose tumors had progressed on prior HER2-directed therapy in the trial received 3.6 mg/kg of T-DM1 by IV every three weeks. The interim findings of the Phase II study include evidence of tumor shrinkage in some patients.

Murfreesboro, Tenn. resident Nancy Fann, 64, had been on at least three chemotherapy treatments since cancer had spread from her lung to her liver and breast, but the tumors kept coming back. In May 2007 she enrolled in the T-DM1 clinical trial.

“The tumors are considerably smaller than they were to begin with,” Fann said. “This drug doesn’t seem to affect me as much as some of the others I’ve been on. I don’t get sick and I haven’t lost my hair.”

Denise A. Yardley, M.D., SCRI’s director of breast cancer research, also presented her research on two trials. Both trials focus on targeted therapies for patients with HER2-positive metastatic breast cancer.

One trial shows preliminary results from a Phase II trial of a combination of Herceptin and the chemotherapy drug oxaliplatin. Twenty-one patients have enrolled in the trial so far, and early results show the treatment is active with little to no significant side effects seen to date.

The other trial focuses on a combination treatment of Avastin and the chemotherapy drug docetaxel for early-stage, metastatic breast cancer. A cohort of patients with HER2-positive disease also receives Herceptin as part of the study. Data for the first 138 patients enrolled indicate the treatment is reasonably well-tolerated without unexpected side effects.

“As knowledge about tumors and tumor biology grows, we’re learning that all breast cancers are not identical,” Dr. Yardley said. “These smart new drugs help target treatment specific to certain types of tumors, causing less damage to healthy cells and reducing side effects.”

-----

www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpae.com
Georgia Front Page

FDA Clears Test that Helps Identify Type of Cancer in Tumor Sample

The U.S. Food and Drug Administration has cleared for marketing a test that can help health care professionals determine what type of cancer cells are present in a malignant tumor.

The Pathwork Tissue of Origin test compares the genetic material of a patient’s tumor with genetic information on malignant tumor types stored in a database.

It uses a microarray technology to analyze thousands of pieces of genetic material at one time. The test considers 15 common malignant tumor types, including bladder, breast, and colorectal tumors.

"The clearance of the Pathwork test is another step in the continued integration of molecular-based medicine into standard practice," said Daniel Schultz, M.D., director of the FDA's Center for Devices and Radiological Health, which oversees medical diagnostics. "In the past, scientists have classified different types of cancers based on the organs in which the tumors develop. With the help of microarray technology, they will be able to classify these types of cancers in a standardized non-reader dependent manner based on the patterns of gene activity in the tumor cells."

The Pathwork Tissue of Origin test is the second in vitro diagnostic multivariate index assay (IVDMIA) device to be cleared by the FDA. In July 2007, the FDA issued a draft guidance document to address premarket pathways and postmarket requirements for IVDMIAs. IVDMIA tests combine the values of multiple variables to yield a single, patient-specific result.

Nearly every cell of the body contains a full set of chromosomes and identical genes but only a fraction of these genes are turned on or expressed in any given cell. Gene expression occurs when certain molecular information contained within DNA is transcribed to create molecules known as RNA. These molecules in turn make the proteins that perform most of the critical functions of cells.

Microarray technology can simultaneously measure gene expression levels of large numbers of genes. Small DNA fragments are placed or arrayed on a slide and then RNA, which has been extracted from the tumor tissue and labeled with a fluorescent marker, is spread over this "microarray."

Since RNA binds to its complementary DNA strand, how much binding occurs indicates how active the gene being evaluated is. This can be determined by putting the array under a scanning microscope and measuring the intensity of the fluorescent light at each point on the array.

Pathwork’s proprietary software converts the scanned image data to gene expression measurements. The gene expression patterns are compared with known gene expression patterns in the database that correspond to different tumor types.

The Pathwork Tissue of Origin test has been found to provide patterns that confirm existing tissue of origin of the 15 common tumor types using standard clinical and pathological information. This accuracy of this test is similar to that achieved by expert pathologists using current standards of practice.

PathChip, the gene expression array used in the Pathwork Tissue of Origin test, is custom-designed for Pathwork Diagnostics of Sunnyvale, Calif., by Affymetrix Inc., of Santa Clara, Calif. PathChip is the first custom Affymetrix gene expression array to be cleared for diagnostic use.

American Cancer Society, National Medical Association Announce Collaboration to Reduce Cancer Disparities

PRNewswire-USNewswire/ -- The American Cancer Society and the National Medical Association today announced a three-year strategic collaboration intended to educate the general public, physicians, and other health professionals about best practices to achieve optimal outcomes in cancer prevention and early detection practices, and treatment among ethnic minority and underserved population groups. This collaboration represents a significant commitment by both organizations to target and eliminate cancer disparities specifically among racial and ethnic minorities by reducing inequalities in access to information and screening services, quality care and treatment, and end-of-life support.

Racial and ethnic minorities can often face numerous obstacles to receiving equal access to quality cancer prevention, early detection and treatment services. Many lack health insurance, live in rural or inner-city communities, have low incomes, and experience language barriers, racial bias and stereotyping. They also tend to receive lower quality health care than whites even when insurance status, income, age and severity of conditions are comparable.

"Promoting increased awareness and understanding of cancer prevention, early detection and treatment to help reduce health disparities is a nationwide priority for the American Cancer Society, said Otis W. Brawley, M.D., chief medical officer, American Cancer Society. "Collaborations with pre-eminent organizations such as the National Medical Association are central to the Society's strategy to reach racial and ethnic minorities with appropriate health information."

"Strategic partnerships with organizations like the American Cancer Society amplify the National Medical Association's ability to touch and impact lives through community action and healthcare provider education," said Nelson L. Adams, III, M.D., president, National Medical Association.

Initial goals for the collaboration include developing and distributing culturally relevant consumer and professional materials that focus on prevention, early detection, and treatment of breast, prostate, and colorectal cancer, as well as proper nutrition and physical activity. The effort will also target faculty and alumni of Historically Black Colleges and Universities, NMA clinical specialty sections, regions, states and local members, community-based organization leaders in the African-American and Hispanic/Latino communities, and large African-American and Hispanic/Latino church congregations nationwide.

This year's collaborative activities also feature a joint cancer symposium called "Collaboration in Addressing Cancer Disparities" for health professionals attending the 2008 National Medical Association Annual Convention and Scientific Assembly, July 26 to 31, 2008. This symposium will take place on Tuesday, July 29 from 9a.m. to 11a.m. ET at the Georgia World Congress Center in Atlanta, Georgia. More than 5,000 health professionals, including physicians, scientists, nurses, medical students, dietitians, and others are expected to attend. The program will provide an overview of the cancer burden facing ethnic and racial minorities and special population groups, its impact on the health of those groups, current progress being made in cancer care, and a discussion of disparities in cancer care and recommendations for addressing them.

Smothered Genes Combine with Mutations to Yield Poor Outcome

Johns Hopkins Kimmel Cancer Center researchers have identified a set of genes in breast and colon cancers with a deadly combination of traditional mutations and “smothered” gene activity that may result in poor outcomes for patients.

The Hopkins team showed that this smothering process, called epigenetic inactivation, contributes to the aggressiveness of breast and colon cancer by disrupting biochemical pathways that normally suppress the runaway growth of cells that is the hallmark of cancer. While mutations alter pathways by rewriting the gene’s DNA code, epigenetic marks affect genes without changing the code itself.

“Until studies like ours, it was easy to think that if we didn’t find gene mutations in certain biochemical pathways linked to breast or colon cancer, then those pathways were normal in such patients,” says Stephen Baylin, M.D., the Virginia and D.K. Ludwig Professor for Cancer Research and deputy director of the Kimmel Cancer Center. “Now we know that, in some patients, the pathways involved with newly discovered mutated genes are often more frequently disrupted by epigenetic mechanisms rather than genetic ones.”

“That’s a powerful insight that could help us diagnose patients quicker, predict the course of their cancer more accurately and in the future treat the disease more effectively,” adds Baylin. A report on this work appeared May 27 in PLoS Medicine.

The team made their discovery using microarray technology – special silicon chips carrying pieces of genetic material that allow thousands of genes to be analyzed at one time. For this study, microarrays were tailored to locate cancer-related genes inactivated by an epigenetic process called DNA methylation. This methylation involves the binding of molecules called methyl groups to elements of DNA called cytosines that are located in a gene’s “on-off switch.” Excess methylation smothers the gene with too many methyl groups and interferes with the gene’s normal protein production, setting the stage for a lethal cancer.

Some 189 mutated genes in breast and colon cancers, previously identified by a Kimmel Cancer Center research team, were screened for methylation by Baylin’s group. They found 36 genes that were infrequently mutated in cancer, but were “hyper”methylated, often in both breast and colon cancers. After reviewing samples from 30 breast and 20 colorectal cancer patients as well as information from public microarray databases, the researchers found 18 of these genes that were strongly linked to poor outcome of patients with tumors carrying these changes.

For most of the genes, the researchers were able to reverse their epigenetic change and reactivate them in test tubes by stripping off excess methyl groups. This suggests that new treatments designed to reverse hypermethylation could be a simpler and more practical approach to treating cancer than strategies that attempt to replace, deactivate or compensate for mutated genes, according to Baylin.

Baylin also believes that the methlylated genes identified in this study could be inactivated in a broader range of cancers as well. That means the current findings could be extended to other cancers, improving the ability of physicians to predict the course of additional types of tumors, he says.

“We’ve learned from this study that we must include both genetic and epigenetic changes when we do future microarray analyses to increase our understanding of the genetic basis of cancer,” Baylin says. “Such information will provide new details about why cancers start and help us identify which cancers will be particularly aggressive in our patients.”

Participants in the study included Timothy Chan, Sabine Glockner, Joo Mi Yi, Wei Chen, Leslie Cope, James Herman, Victor Velculescu, Kornel Schuebel, and Nita Ahuja of Johns Hopkins, and Leander Van Neste of Ghent University, Belgium.

This work was supported by the National Institute of Environmental Health Sciences and the National Cancer Institute.

One-Day Breast Cancer Treatment Saves Lives in Less Time

(ARA) – For many patients, a cancer diagnosis is no longer a fatal one. However, the comfort that a patient’s condition is treatable is often accompanied by dread of the grueling treatment that will be needed to save his or her life. But a new therapy holds hope for treating some cancers in just a single day, rather than through months of harsh radiation therapy.

Arleen Sharwell, 65, a New York resident and mother of two, was among the millions of women who received a diagnosis of breast cancer last year. After the initial shock of the diagnosis, Sharwell discussed her treatment options with her breast surgeon on Long Island. They settled on a lumpectomy surgery followed by five to six weeks of traditional radiation therapy.

Through a family connection, Sharwell learned of a procedure that can eliminate weeks of costly, physically demanding post-operative radiation treatment. The procedure, known as intraoperative electron beam radiation therapy, uses a device called the Mobetron, from IntraOp Medical (www.intraopmedical.com), to deliver a single dose of radiation at the time of surgery. Because the procedure applies the radiation directly to the cancer-affected area, treatment times are shorter, recovery is faster, side effects are fewer and cosmetic results are better than those often experience by patients who go through traditional radiation treatment.

Recent clinical studies, including one from renowned breast surgeon Dr. Umberto Veronesi of Milan’s European Institute of Oncology, have shown that a single dose of radiation at the time of surgery could be equivalent to a full six-week course of traditional post-operative radiation treatment. This treatment is being widely adopted in many international health centers, as it provides a cost-effective way to treat breast cancer, while offering patients better quality of life.

After researching the Mobetron and the single dose treatment, Sharwell passed the information to her doctor. She assumed her doctor would take an active role in helping her to connect with a hospital that offered the treatment, but Arleen’s doctor was uninterested in hearing about the Mobetron. More than that, he openly questioned its effectiveness. “Arleen,” he said, “We have better things here.”

Sharwell turned to Dr. David Ollila from the University of North Carolina in Chapel Hill. She met with Ollila, associate professor and surgical director for the multi-disciplinary breast and multidisciplinary melanoma programs at UNC, and Dr. Joel Tepper, professor and former chair of radiation oncology, to see if she was a candidate for the device. They were quickly able to confirm that she was a candidate, and the doctors scheduled her surgery to be conducted just a few days after the initial meeting.

The day of her operation, Arleen arrived at the hospital at 7 a.m. and finished her surgery and two-minute single dose of radiation from the Mobetron that same day. Dr. Tepper delivered a single dose of radiation to the tumor bed, pinpointing the exact area that required radiation so that healthy tissue was left unharmed. Dr. Ollila then safely removed the lump from Sharwell’s breast.

Sharwell never imagined that she would be treated as an outpatient for breast cancer. “The next day my family came in for lunch and I was shopping in Chapel Hill. I felt fine,” she says.

“The Mobetron made what seemed to be a dreadful situation something that I could overcome,” Sharwell says. “I’ve been trying to get the word out so that other patients can benefit from this fast and remarkable treatment.” She is also impressed with the way her breast has healed since the surgery. “I couldn’t imagine going to a plastic surgeon and having it look any better.”

Sharwell says cancer patients should never just accept what their doctor tells them. They must conduct their own research -- and always get a second opinion.

Courtesy of ARAcontent

FDA Approves New Genetic Test for Patients with Breast Cancer

The U.S. Food and Drug Administration has approved a novel genetic test for determining whether patients with breast cancer are good candidates for treatment with the drug Herceptin (trastuzumab).

The SPOT-Light HER2 CISH kit is a test that measures the number of copies of the HER2 gene in tumor tissue. This gene regulates the growth of cancer cells.

A healthy breast cell has two copies of the HER2 gene, which sends a signal to cells, telling them when to grow, divide and make repairs. Patients with breast cancer may have more copies of this HER2 gene, prompting them to overproduce HER2 protein so that more signals are sent to breast cells. As a result, the cells grow and divide much too quickly.

“When used with other clinical information and laboratory tests, this test can provide health care professionals with additional insight on treatment decisions for patients with breast cancer,” said Daniel Schultz, M.D., director of the FDA’s Center for Devices and Radiological Health.

The SPOT-Light test counts the number of HER2 genes in a small sample of removed tumor. The removed piece is stained with a chemical that causes any HER2 genes in the sample to change color. This color change can be visualized under a standard microscope, eliminating the need for the more expensive and complex fluorescent microscopes required to read assays already on the market. Unlike existing tests, the SPOT-Light allows labs to store the tissue for future reference.

Patients who over-produce HER2 protein are typically treated with the drug Herceptin, which targets HER2 protein production. This helps to stop the growth of HER2 cancer cells.

The FDA based its approval of the SPOT-Light test on a study using tumor samples from patients with breast cancer in the United States and Finland. These studies confirmed that the test was effective in determining how many HER2 genes were in these patients.

SPOT-Light is manufactured by Invitrogen Corp. of Carlsbad, Calif. Herceptin is manufactured by Genentech, of San Francisco, Calif.

-----

www.fayettefrontpage.com
Fayette Front Page
Community News You Can Use
Fayetteville, Peachtree City, Tyrone

Outreach Initiatives Lead to Shift in Stage of Breast Cancer Diagnosis in African-American Women

Researchers at Emory University have determined that community education outreach and internal navigation programs lead to a significant shift in stage at diagnosis of breast cancer among African-American women.

Sheryl Gabram, MD, an Emory Winship Cancer Institute surgical oncologist, and her colleagues report a doubling in the proportion of cases caught at the earliest stage and a nearly reciprocal drop in the proportion of cancers at most advanced stage in African-American women who participated in community education or internal navigation programs.

The research suggests that initiatives aimed at raising awareness and utilization of breast cancer screening may improve breast cancer survival rates for African-American women, who have a higher risk of death from the disease compared to whites. The study is published on line this month and in the August 1, 2008 issue of CANCER, a peer-reviewed journal of the American Cancer Society.

A disproportionate number of deaths from breast cancer occur in African-American women, a disparity attributed to later stage of disease at diagnosis and diagnosis at an earlier age. Treatment differences may also contribute to the higher risk of mortality.

To assess the effectiveness of outreach programs on breast cancer stage among African-American women, Dr. Gabram, who also is director of the AVON Comprehensive Breast Center at the Georgia Cancer Center for Excellence at Grady Memorial Hospital in Atlanta, reported on a program implemented in 2001 with two components: Community Health Advocacy and Patient Navigation. The Community Health Advocacy component includes public educational programs that encourage mammography screening, teach the importance of breast self exams, and instruct individuals to see a trained healthcare provider.

The Patient Navigation component involves breast cancer survivors who communicate directly with all patients who have been diagnosed with breast cancer in the AVON Breast Center. Patient Navigators (PNs) encourage patients to follow-up with recommended medical care and access needed resources such as finances, transportation, and support services.

Between 2001 and 2004, the program conducted a total of 1,148 community interventions for more than 10,000 participants. During that same time period, a total of 487 patients were identified, diagnosed, and treated for breast cancer at the AVON Comprehensive Breast Center (89 percent African American, 5 percent Caucasian, 2 percent Hispanic, and 4 percent other race/ethnicity).

Dr. Gabram and her team found that there was a doubling in the proportion of Stage 0 non-invasive breast cancers (from 12.4 percent to 25.8 percent) over the study period, while the proportion of women diagnosed with Stage IV invasive breast cancers dropped from 16.8 percent to 9.4 percent.

"This reciprocal deviation of Stage 0 versus Stage IV cancers has implications on prognosis, and ultimately outcome for these women if recommended treatment guidelines are followed," say the authors. They, along with leadership from Emory University's Rollins School of Public Health team, are currently conducting studies to see if the Patient Navigation program successfully influences patients to accept treatment recommendations and to adhere to appointments after they are diagnosed with breast cancer. Research has revealed that many patients with breast cancer refuse or do not receive appropriate therapy.

The authors concluded that programs with Community Health Advocates (CHAs) who encourage mammography screening and stress the importance of early diagnosis should be jointly emphasized with the efforts of the Patient Navigators (PNs) who encourage acceptance of and adherence to treatment standards.

Article: "Effects of an outreach and internal navigation program on breast cancer diagnosis in an urban cancer center with a large African-American population." Sheryl G.A. Gabram, Mary Jo B. Lund, Jessica Gardner, Nadjo Hatchett, Harvey L. Bumpers, Joel Okoli, Monica Rizzo, Barbara J Johnson, Gina B Kirkpatrick, and Otis W. Brawley. CANCER; Published Online: June 23, 2008 (DOI: 10.002/cncr.23568); Print Issue Date: August 1, 2008.