Wednesday, June 09, 2010
Genetic and Clinical Predictors for Breast Cancer Risk Assessment and Stratification Among Chinese Women
CONTEXT AND CAVEATS
Prior knowledge
Most of the genetic variants identified in genome-wide association studies of breast cancer conducted primarily among women of European ancestry have not been validated in Asian women. Consequently, no risk assessment model that incorporates both genetic and clinical predictors is currently available to predict breast cancer risk in this population.
Study design
Case–control study evaluating associations between the 12 single-nucleotide polymorphisms identified as risk variants and the risk of breast cancer among Chinese women participating in the Shanghai Breast Cancer Study as well as the cumulative risk of breast cancer associated with combinations of these risk variants. A risk assessment model that incorporates both newly identified genetic variants and traditional risk factors was developed, and its performance in risk prediction was evaluated.
Contribution
Eight of the 12 single-nucleotide polymorphisms were also associated with the risk of breast cancer among Chinese women. An aggregate measure of the combined effect of multiple genetic risk variants had moderate discriminatory accuracy by itself but in combination with established risk factors for breast cancer showed promise for stratifying women into high- vs low-risk groups.
Implications
A risk assessment model that includes both genetic markers and clinical predictors may be useful to classify Asian women into relevant risk groups for cost-efficient screening and other prevention programs.
Limitations
The moderate discriminatory accuracy provided by the full risk assessment model established in this study is inadequate for cancer diagnosis and screening. The absolute risk estimates provided by the model would be applicable only to populations with rates comparable to those of Shanghai.
Paradigm Change Suggested for Ovarian Cancer
Note: this website requires registration/free
"Women with biochemically recurrent ovarian cancer who take tamoxifen can gain an additional month of progression-free survival and have fewer side effects than women taking thalidomide, according to a study presented at the recent Society for Gynecologic Oncology’s annual meeting (abstract 2)"
“This is a very well-tolerated, very inexpensive drug, and now we have a randomized controlled, Phase III trial conducted by a cooperative group showing that it actually improves the time to subsequent disease progression,” said Maurie Markman, MD, vice president for clinical research at the University of Texas M.D. Anderson Cancer Center in Houston, who was not involved with the study...."cont'd
MedEffect Canada - 2010 - Advisories, Warnings and Recalls
June
* CIPROFLOXACIN INJECTION - Voluntary Recall
o Notice to Hospitals [2010-06-09]
per Wiki: "Ciprofloxacin is marketed worldwide with over three hundred different brand names. In the United States, Canada and the UK, it is marketed as Baycip, Ciloxan, Ciflox, Cipro, Cipro XR, Cipro XL, Ciproxin and most recently, Proquin. Additionally, ciprofloxacin is available as a generic drug under a variety of different brand names and is also available for limited use in veterinary medicine."
Survival benefit from ovarian metastatectomy in colorectal cancer patients with ovarian metastasis: a retrospective analysis
Abstract
PURPOSE: A recent study demonstrated that colorectal cancer (CRC) with ovarian metastases was less responsive to chemotherapy compared with extraovarian metastases. Hence, the ovary may actually represent a "sanctuary" for metastatic cells from CRC. The aim of the study was to investigate the impact of ovarian metastatectomy on survival of CRC patients with ovarian metastasis.
Oncology Videos - ASCO 2010 Highlights (American Society of Clinical Oncology) Dr. Bradley Monk MD of the University of California Irvine talks about gynecological oncology, GOG 218, ovarian cancer, and angiogenesis
Note: Ascites/Avastin as single agent and or chemo GOG 218
Hereditary Cancer in Clinical Practice | Full text | Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different risk profiles may influence clinical management
Table 2:
Median age and range at diagnosis of Lynch syndrome
MLH1 MSH2 MSH6
Colorectal cancer 47 (25-79) 44 (20-82) 53 (32-84)
Endometrial cancer 51 (46-54) 46 (36-55) 56 (47-67)
Ovarian carcinoma 52 (52-52) 47 (45-48) 49 (35-51)
Small bowel cancer 54 (54-54) 36 (23-49) -
Transitional cell carcinoma - 58 (32-59) -
"The aim of the present study was to calculate the cumulative risk
of LS related cancers in proven MLH1, MSH2 and MSH6 mutation carriers."
"Furthermore, some studies have suggested that extracolonic cancers are more often observed in MSH2 mutation families compared to MLH1 mutation families."
press release: Clarient Receives Patents for Taxane Biomarker - TLE3 (gene)
Note: Transducin-like enhancer protein 3 is a protein that in humans is encoded by the TLE3 gene
"Clarient, Inc., a premier technology and services resource for pathologists, oncologists and the pharmaceutical industry, today announced that the United Kingdom Patent Office has granted a U.K. patent on the Company's TLE3 biomarker, a marker which may be used to predict which cancer patients will respond favorably to taxane therapy. In addition, the Company has received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for a U.S. patent on the TLE3 biomarker. Other patents for the TLE3 biomarker are pending in the U.S., Canada, Japan, China, India and elsewhere in Europe.
The U.S. patent will cover uses of the TLE3 biomarker in breast cancer. The U.K. patent covers uses of TLE3 in breast, lung and ovarian cancers.
Taxanes are important cancer therapeutics which, in combination with other cancer therapies, can markedly improve a patient's response rate to therapy. However, taxanes also carry with them a significant incidence of severe side effects, making it important to identify which patients will most likely benefit from the therapy.
"Given the frequent prescription of taxanes in the U.S., the U.K. and elsewhere in Europe and the world, we are very excited about the granting of these patents and the protection they provide our taxane sensitivity marker," said Clarient Vice Chairman and CEO Ron Andrews."
Munk Debates - The Debates
watch, listen and read:
June 7, 2010
Topic: I would rather get sick in the United States than Canada.
Pro Dr. William Frist Dr. David Gratzer
Con Dr. Howard Dean Dr. Robert Bell
Canadians warming to controversial medical user-fees, poll finds - The Globe and Mail
Note: see prior posting regarding 'Monk Debates'
WHO Responds to BMJ Report - Medical News
Note: see prior posting regarding criticisms of WHO (June 2010)
"Financial ties to the pharmaceutical industry did not play a role in the declaration and handling of the H1N1 influenza pandemic, said Margaret Chan, MD, MPH, secretary-general of the World Health Organization.
"At no time, not for one second, did commercial interests enter my decision-making," she wrote in a letter to the editors of the BMJ, which published a report last week detailing undisclosed conflicts of interest among researchers advising the WHO.
The implication of the report was that these ties to industry may have influenced some of the guidance the advisers were giving to the WHO.
"Without question, the BMJ feature and editorial will leave many readers with the impression that WHO's decision to declare a pandemic was at least partially influenced by a desire to boost the profits of the pharmaceutical industry," Chan wrote. "The bottom line, however, is that decisions to raise the level of pandemic alert were based on clearly defined virological and epidemiological criteria. It is hard to bend these criteria, no matter what the motive."
Although Chan disagreed with any implication of untoward influence from industry, she agreed that difficult questions about conflicts of interest are warranted...."
Repeat posting: Controversies in Targeted Therapy: Management of Recurrent Ovarian Cancer—Practical Case-Based Discussions CME (3)
1 Controversies in Targeted Therapy: Management of Recurrent Ovarian Cancer—Webcast (Activity OCPS01)1942 (MARCH 2010)
2 Using Targeted Therapies in a Real-World Setting—Podcast Series (Activity OCPS02)1943.01 (APRIL 2010)
3 Personalizing Treatment and Managing Patient Concerns—Podcast Series (Activity OCPS03)1943.02 (MAY 2010)
Registry Data Point to Diclofenac as Deadliest NSAID
Note: discusses adverse/risks of numerous NSAID's
Correlogic Systems Obtains CE Mark for OvaCheck® | SYS-CON MEDIA
media: June 9th: "Correlogic Systems, Inc. announced today that OvaCheck, the company's blood test for the detection of epithelial ovarian cancer, has fulfilled European Union regulatory requirements (CE marking) for distribution and sale of the test. The path is now cleared for the test to be made available to patients in Europe through their physicians...."
Molecular blockade of VEGFR2 in human epithelial ovarian carcinoma cells
Note: ACOR members see notes from Chicago
Abstract (in research/technical):
"Our findings highlight the possible confounding events that may affect the usefulness of RNAi in a therapeutic setting for disrupting EOC cell survival in ascites."
Endocrine tumors of the appendix: a pathologic review
Abstract
CONTEXT: Although rare, appendiceal endocrine tumors are the most common neoplasms of the appendix. Pathologic analysis is important for guiding the management of patients.
OBJECTIVE: To provide recent data that focus on the pathology of endocrine tumors of the appendix including classifications and guidelines for patient management.
DATA SOURCES: A review of the recent literature including TNM classifications and patient management guidelines.
CONCLUSIONS: Appendiceal endocrine tumors are separated into 2 main groups: classic endocrine tumors and goblet cell carcinoids. They can be classified according to World Health Organization and TNM classifications. Evaluation of their prognoses and risks of malignancy, according to these classifications, depends on several parameters including tumor size, proliferation rate, and infiltration of appendiceal wall and mesoappendix. Most patients with classic endocrine tumors of the appendix have a favorable prognosis. Indications for postappendectomy, complementary surgery, which are still controversial, especially for tumors between 1 and 2 cm, are presented and discussed. In contrast, in patients presenting with a goblet cell carcinoid, a right hemicolectomy after the initial appendectomy is considered the standard surgical intervention.
Appendiceal mucinous neoplasms: controversial issues - pathology
Abstract:
"...reviewed is the largely resolved controversy about whether ovarian mucinous tumors in this setting are separate primaries or are metastases from the appendiceal tumor."
June 8, 2010 SGO Statement on GOG 218 Phase III Trial Study Results (Avastin)
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Scaling Laws for Plasma Concentrations and Tolerable Doses of Anticancer Drugs -- Cancer Research
Abstract:
General scaling laws are developed for projecting measurements of the plasma concentrations of anticancer drugs from laboratory animals to humans and among humans of different sizes. Associated scaling laws for critical drug doses are established from these laws. Broad categories of single and periodic i.v. bolus dosings are considered. Validity of the relations is shown using measurement from the literature for several well-known cytotoxic agents. The scaling theory is also shown to apply to novel anticancer drugs now available or presently under development, as represented by the p.o. administered prodrug capecitabine, the gene silencing inhibitor zebularine, and the blood vessel inhibitor bevacizumab(Avastin). Scaling considerations for the modern practice of combination chemotherapy are also discussed.
JAMA -- Abstract: Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease, May 12, 2010
"Conclusions Two genetic loci for AD were found for the first time to reach genome-wide statistical significance. These findings were replicated in an independent population. Two recently reported associations were also confirmed. These loci did not improve AD risk prediction. While not clinically useful, they may implicate biological pathways useful for future research."
Future Oncology - Summary - Different volatile signals emitted by human ovarian carcinoma and healthy tissue
Note: in plain english this refers to a small study using 'electronic' smelling (eg. past articles regarding dogs with the ability to 'smell' ovarian cancer)
Future Oncology -- Full Text - Cancer immunotherapy: focusing on the young, neglecting the old
"...Undoubtedly we should pay more attention to the effect that aging has on the immune system. To optimally stimulate an anti-tumor immune response in the old, it is necessary to identify and understand the intrinsic defects of the old immune system and use relevant models that closely reflect those of cancer patients, where self-tolerance and aging are present simultaneously. Then it will be possible to develop cancer immunotherapeutic strategies that are customized to be effective in the young and the old."
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