Eisai Announces Extension Of FDA Review Of Drug Application For Investigational Agent Eribulin Mesylate

Eisai Inc. announced today that it has received notification from the U.S. Food and Drug Administration (FDA) that the agency expects to complete priority review of the eribulin mesylate New Drug Application (NDA) for locally advanced or metastatic breast cancer on or before December 30, 2010, which is a three month extension from the original Prescription Drug User Fee Act (PDUFA) action date of September 30, 2010.


The extension is a result of the agency classifying recent responses to questions regarding the chemistry, manufacturing and controls (CMC) section of the NDA as a major amendment to the NDA. The new action date will give the agency additional time to review the information submitted for this complex synthetic process.


In addition to the U.S. FDA priority review, eribulin is currently under active regulatory review in Japan, the European Union (EU), Switzerland and Singapore.


Eisai defines oncology as a therapeutic area of focus and is committed to developing novel anti-cancer agents and treatments for supportive care. With these efforts, Eisai seeks to further address the diversified needs of patients and families affected by cancer, and their healthcare professionals.


About Eribulin


Eribulin mesylate (E7389) is an investigational agent being evaluated as a potential treatment for locally advanced or metastatic breast cancer. A non-taxane, microtubule dynamics inhibitor, eribulin is a synthetic analog of halichondrin B, which is derived from a natural product isolated from the marine sponge Halichondria okadai. Eribulin is the state of the art in modern synthetic chemistry, which has 826 of molecular weight, 62 steps of total synthetic route and 19 chiral carbons.


About Advanced or Metastatic Breast Cancer


Advanced or metastatic breast cancer occurs when a malignant tumor in the breast spreads from its original site to other parts of the body. Approximately 50 percent of women worldwide initially diagnosed with breast cancer are expected to develop recurrent or metastatic disease within 15 years of their first diagnosis. Only one in five women with metastatic breast cancer survives longer than five years. In the U.S., an estimated 155,000 women are currently living with metastatic breast cancer, and that number is projected to increase to 162,000 by 2011.


Source:

Eisai Inc.

Researchers Identify Gene That Regulates Breast Cancer Metastasis

Researchers at The Wistar Institute have identified a key gene (KLF17) involved in the spread of breast cancer throughout the body. They also demonstrated that expression of KLF17 together with another gene (Id1) known to regulate breast cancer metastasis accurately predicts whether the disease will spread to the lymph nodes. Previously, the function of KLF17 had been unknown.


Deaths of most breast-cancer patients are the result of metastasis, a complex, multi-step, and poorly understood process. "Identifying the gene that suppresses the spread of tumor cells and the mechanisms by which this suppression occurs can lead to the discovery of new markers of metastasis and potential targets for cancer prevention and treatment," says Qihong Huang, M.D., Ph.D., assistant professor at The Wistar Institute and senior author of the study.


In this study, which appears in the October on-line issue of Nature Cell Biology, Huang and colleagues introduced a genetic screen targeting 40,000 mouse genes into mammary tumor cells that do not usually spread, and then transplanted those cells to the mammary fat pads in mice where they would be expected to remain. Through RNA interference (RNAi) technology, they then reduced the expression of a metastasis-suppressor gene in five mice, one of which developed lung metastases in seven weeks. RNA retrieved from the metastasized cells corresponded to KLF17.


To determine whether KLF17 played a similar role in human breast-cancer metastasis, the researchers knocked down KLF17 expression in a tagged human-breast-cancer cell line and then transplanted these cells along with a control group still expressing KLF17 into mammary fat pads of mice. Within eight to 10 weeks, lung metastases developed in the KLF17-deficient cells, whereas the control cell set did not metastasize, demonstrating that knockdown of KLF17 expression also promotes the spread of human breast-cancer cells.


The researchers also were interested specifically in genes whose expression were increased in KLF17 knockdown cells but decreased in KLF17 overexpressing cells or vice versa. In collaboration with Professor Louise C. Showe, Ph.D. at the Wistar Institute, they found the significant genes that met these criteria. Among them, the gene Id1 was found to be up-regulated in KLF17 knockdown cells and down-regulated in KLF17 overexpressing cells. Recent findings suggest that Id1 is deregulated in various types of cancers and is important in the development of embryonic stem cell like phenotypes in cancer cells.


To further investigate the interactions of KLF17 and Id1, the Huang lab scanned a DNA segment of mouse Id1 and found two potential KLF17 binding sites. To examine the effect of Id1 upregulation in tumor metastasis in vivo, the team generated tagged mouse and human cell lines expressing mouse or human Id1, respectively. Following transplantation back into the mice, lung metastasis developed from Id1-upregulated cells but not in controls, demonstrating that Id1 expression promotes tumor metastasis in vivo.


Further characterization of KLF17 is an ongoing subject of study for Wistar researchers. "We are continuing to examine ways to activate KLF17 and the methods by which that process slows or prevents cancer metastasis," Huang says.


The lead author on the study is Wistar's Kiranmai Gumireddy, Ph.D. Study investigators also included Professor Louise C. Showe, Ph.D.; and Anping Li, from the Wistar Institute; Andres J. Klein-Szanto, M.D.; from Fox Chase Cancer Center; and Phyllis A. Gimotty, Ph.D., Dionyssios Katsaros, M.D., Ph.D.; George Coukos, M.D., Ph.D.; and Lin Zhang, M.D.; from the University of Pennsylvania.


The project was supported by the Breast Cancer Alliance, Pardee Foundation, V Foundation, Commonwealth Universal Research Foundation of the Pennsylvania Department of Health, the National Cancer Institute, and the Mary Kay Ash Charitable Foundation.


The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today's Discoveries Tomorrow's Cures.


Source: Wistar Institute

Everolimus May Help Thwart Trastuzumab Resistance In Breast Cancer Patients

BERLIN - New data identify a possible role for everolimus in reversing or delaying the onset of trastuzumab resistance in breast cancer patients.


The findings are from two trials presented at the joint 15th European Cancer Organization (ECCO) and 34th European Society for Medical Oncology (ESMO) Multidisciplinary Congress.


Everolimus is an oral mTOR inhibitor that is approved for the treatment of patients with advanced renal cell carcinoma whose disease has progressed on or after treatment with vascular endothelial growth factor-targeted therapy.


The drug has also been shown to reverse trastuzumab resistance caused by PTN loss in preclinical studies and additionally has shown anti-tumor activity as a single agent in patients with metastatic breast cancer.


Dr. Sara Hurvitz, with the UCLA School of Medicine, and colleagues conducted a study to establish the feasible dose schedule for daily and weekly administration of everolimus combined with weekly trastuzumab and paclitaxel in patients with HER-2 overexpressing metastatic breast cancer whose disease had progressed during or after trastuzumab therapy.


Results in 33 patients showed that the combination was well tolerated and that the recommended starting dose for the phase II study is 10 mg daily.


Combination therapy involving everolimus, paclitaxel, and trastuzumab demonstrated "encouraging" efficacy in this heavily treated population of patients refractory to trastuzumab and taxanes. In particular, everolimus demonstrated activity in all patients who were evaluable for efficacy and assigned to the 5 mg everolimus treatment group.


The disease control rate was 85% (28 of 33 evaluable patients).


Biomarker results were similar to those observed during everolimus monotherapy in patients with metastatic renal cell cancer and suggest that the activity of everolimus is mediated in part through inhibition of VEGF-A-driven angiogenesis, Dr. Hurvitz said.


In a second study, similar results were obtained with the combination of everolimus (5 mg daily or 20 or 30 mg weekly) with vinorelbine and trastuzumab.


Dr. Fatima Cardoso, with the Jules Bordet Institute in Brussels, reported that the combination was feasible and tolerable in a similar heavily pretreated group of breast cancer patients and also showed promising clinical activity with a relevant long-term disease control. The disease control rate was 80% (37 of 46 evaluable patients).


In the study, there was no limit to the number of prior antineoplastic treatments.



Overall, 30 patients were assigned to a 5 mg daily dose of everolimus, and 20 patients received a 20 or 30 mg weekly dose.


Dr. Cardoso said that the addition of everolimus can bolster the therapeutic activity of vinorelbine and trastuzumab and reverse or postpone the onset of trastuzumab resistance.


Written by Jill Stein

Jill Stein is a Paris-based freelance medical writer.

Clinical Study of Sentinel Breast Scan

Infrared Sciences Corporation (ISC) announced today that they have commenced a Clinical Study with the New York Presbyterian Hospital-Weill Medical College of Cornell University in New York City. The protocol will focus on determining the adjunctive effectiveness of the Infrared Sciences Sentinel BreastScan imaging system for early breast cancer detection. Study patients will have been scheduled for a breast biopsy, either by mammography or ultrasound. The Study will correlate the outcomes of radiology, pathology, and the Sentinel BreastScan.



"We are pleased and excited to commence this study with Cornell, and we believe that the information obtained from the Sentinel system will prove it to be a highly effective adjunctive tool in the war against breast cancer" explained ISC Vice President, Matthew Campisi. "The Sentinel system provides a new physiological dimension to breast health information that is not available from any other fully non-invasive testing method."



Sentinel BreastScan is a painless, touchless, non-invasive procedure offered to women of any age. The technology is based on advanced digital infrared imaging that is combined with sophisticated software employing artificial intelligence techniques. Immediately following the 4-minute test, it provides the doctor with a fully-interpreted, objective report. It is the only system like it in the world.



Sentinel BreastScan is intended to be an adjunctive procedure and does not replace mammography or ultrasound, or stand alone as a single test that can determine overall breast health.



For more information contact Infrared Sciences Corporation., at 213 Hallock Road, Suite 5, Stony Brook, New York, 11790. TEL: 631 240-9106, FAX: 631 240-9108, infoinfraredsciences, or visit infraredsciences.

Follow-Up Study Confirms Link Between Migraines And Reduced Breast Cancer Risk

The relationship between migraine headaches in women and a significant reduction in breast cancer risk has been confirmed in a follow-on study to landmark research published last year and conducted by scientists at Fred Hutchinson Cancer Research Center. The new study found a 26 percent reduced risk of breast cancer among both premenopausal and postmenopausal women with a clinical diagnosis of migraines.



The study appears in the July 2009 issue of Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research. It was led by Christopher I. Li, M.D., Ph.D., a breast-cancer epidemiologist and associate member of the Hutchinson Center's Public Health Sciences Division. Li led the first-of-its-kind study linking migraines with breast cancer risk reduction that was published in the same journal last November.



This time researchers found that the risk reduction remained statistically similar regardless of a woman's menopausal status, her age at migraine diagnosis, use of prescription migraine medications or whether she avoided known migraine "triggers" such as alcohol consumption, smoking and taking hormone replacements. These triggers are also well-established breast cancer risk factors.



Some key differences between this study and the initial one that discovered the link include:
The sample size was more than four times larger this time - more than 4,500 cases and controls versus about 1,000 each in the first study - and was more diverse geographically, drawing women from five metropolitan areas instead of only one. "From an epidemiological perspective, having a larger and more diverse study in its underlying population helps in replicating the finding," Li said.


The age range of women studied was wider this time, 34-64 years of age versus 55-74 years old. "We were able to look at whether this association was seen among both pre-menopausal and post menopausal women," Li said. "In breast cancer this is relevant because there are certain risk factors that are different between older and younger women. In this study we saw the same reduction in breast cancer risk associated with a migraine history regardless of age."


Researchers were able to ascertain whether women in the study had lifestyle behaviors that are known migraine triggers - alcohol consumption, smoking and taking hormone replacement therapy. Researchers posited that perhaps women who had migraines drank and smoked less and didn't take hormone replacements. "But in this study we looked at women who never drank, never smoked and who also didn't use hormones and found the same association within each of those groups, suggesting that the association between migraine and reduced breast cancer risk may be independent of those other factors and may stand alone as a protective factor," he said.

What remains unknown is how migraine confers its apparent protection against breast cancer. "We know that migraine is definitely related to hormones and that's why we started looking at this in the first place," Li said. "We have different ideas about what may be going on but it's unclear exactly what the biological mechanisms are."



In the meantime, research on migraines and breast cancer continues. Li and his colleagues are conducting a follow-up investigation among the women in the first study to determine the types, timing, intensity and severity of their migraines in hopes that the data may elicit additional clues.



And, the research group has submitted a third study for publication that found that the association between migraine and reduced breast cancer risk holds up independent of whether women with migraine took non-steroidal anti-inflammatory drugs such as aspirin and ibuprofen. Earlier studies linked these medications to reduced breast cancer risk as well.



Source:
Dean Forbes


Fred Hutchinson Cancer Research Center

Possible Negative Effect Of Disadvantaged Neighborhoods On Breast Cancer In Black Women

Researchers at the University of Chicago are studying possible connections between living in disadvantaged neighborhoods and the development of early onset breast cancer in a path-breaking project led by Sarah Gehlert, Director of the Center for Interdisciplinary Health Disparities Research.



The initiative is funded with a $9.7 million grant from National Institutes of Health and is the first to use animal models to help determine what the biological factors might be behind the development of certain forms of breast cancer.



Gehlert is lead author of the paper discussing the findings, titled "Targeting Health Disparities: Linking Upstream Determinants to Downstream Interventions" published in the current issue of Health Affairs.



Joining Gehlert, who is the Helen Ross Professor in the School of Social Service Administration at the University, as an author in the paper is Olufunmilayo Olopade, the Walter L. Palmer Distinguished Service Professor in Medicine and Human Genetics at the University. As part of the work of the CIHDR, Olopade and other scholars studied early onset breast cases in Nigerian women, whose genetic heritage is similar to African-Americans because the ancestors of African Americans largely came from West Africa.



African-American, like Nigerian women, develop breast cancer earlier than white women, and it is often much deadlier. While white women usually develop the disease after menopause, it develops prior to menopause among women of African heritage.



Co-author Martha McClintock, the David Lee Shillinglaw Distinguished Service Professor in Psychology at the University, carried out the animal modeling by studying the development of spontaneous mammary tumors in socially isolated rats.



Researchers are studying 230 black women with newly diagnosed breast cancers living in predominantly black Chicago neighborhoods to learn about environmental factors, such asneighborhood features that might lead to social isolation.



"These women experience stress from dealing with situations they cannot control, from seeing crime in their neighborhood, from being afraid to go out, and not being able to form casual relationships with their neighbors that might make them feel safe," Gehlert said.



By studying multiple pathways to the development of the disease, leading from environmental challenges to gene regulation, the team will help inform policy makers about making decisions in how to create cost-effective interventions, McClintock said.



The team said that the women's vulnerability to stress and social isolation could be reduced if communities work with neighborhood and city leaders to reduce building vacancies and establish networks that would give women a greater feeling of control over their environments.







Other authors in the study are University researchers Dana Sohmer, Tina Sacks and Charles Mininger.



Source: William Harms


University of Chicago

Enrollment Restrictions For California Breast Cancer Screening Program Lead To Reduced Services

Many California mammography clinics and mobile care units have suspended or reduced services since the state's Every Woman Counts program halted enrollment and raised age eligibility requirements for no-cost breast cancer screenings and diagnostic services, the AP/San Francisco Chronicle reports. The California Department of Public Health imposed a temporary enrollment freeze from Jan. 1 to July 1 to reduce the number of mammogram beneficiaries to 259,000 this fiscal year, from 311,000 last year.

DPH also increased the minimum age for program participants from 40 to 50, mirroring recent U.S. Preventive Services Taskforce guidelines stating that most women should begin screenings at age 50, rather than 40. According to Sean Tuffnell, a public policy expert for the Susan Komen Foundation for the Cure, California is the only state that has adjusted its mammogram eligibility rules since the recommendations were issued.

Several clinics and mobile care units reported drops in patient volume since the program changes. For example, the Elizabeth Center for Cancer Detection in Los Angeles reported a 34% decrease in its patient load during the first three months of 2010. The clinic temporarily closed in April but now offers services three days per week. CEO Don Cook said the clinic faces permanent closure at the end of May.

Mobile Mammography Screening President Deborah Wright said she laid off all of her 40 mammography technicians and suspended service at her 11 mobile units after the program changes. The mobile clinics screened 1,600 patients in January, down from a monthly average of 6,250 patient screenings in 2009.

For fiscal year 2009-2010, Every Woman Counts received $61.3 million in funding, a nearly $10 million increase from the previous fiscal year. However, officials said the funding reflected a one-time budget boost from an unspent tax and did not cover cost increases.

State Sen. Jenny Oropeza (D) has introduced a bill (SB 836) that would reinstate funding for the program. The legislation is before the state Senate Appropriations Committee (Mohajer, AP/San Francisco Chronicle, 5/9).


Reprinted with kind permission from nationalpartnership. You can view the entire Daily Women's Health Policy Report, search the archives, or sign up for email delivery here. The Daily Women's Health Policy Report is a free service of the National Partnership for Women & Families, published by The Advisory Board Company.


© 2010 The Advisory Board Company. All rights reserved.