Friday, May 07, 2010
Note: easier to read Medscape article from previous blog post
"Cancer researchers at Princess Margaret Hospital (PMH) have discovered that the ovarian hormone progesterone plays a pivotal role in altering breast stem cells, a finding that has important implications for breast cancer risk.......The findings, published online today in Nature (10.1038/nature09091; http://dx.doi.org/), are significant because reproductive history is among the strongest risk factors for breast cancer, says principal investigator Rama Khokha, a molecular biologist at Ontario Cancer Institute and the Campbell Family Cancer Research Institute, PMH. Other major known risk factors are age, genetics and breast density."
Risk Tools Limited in Their Ability to Predict Development of Breast Cancer including Editorial Comment
....Major Limitations Exist
According to the researchers, these models each have major limitations. Most notable is that the models rely on known risk factors, given that up to 60% of breast cancers occur in the absence of known risk factors. In addition, with the exception of the Gail model, these tools have not been well validated, and they also do not include nonhereditary risk factors. However, even the Gail model has limited ability to discriminate between individuals at risk, especially those in higher-risk groups, according to the study authors.
To date, no existing model is "totally able to discriminate between families that do and do not have mutations or between women who will and will not develop breast cancer," they write. "Steady and incremental improvement in the models are being made, but these changes require revalidation."
Other risk factors, such as mammographic density, weight gain, and serum steroid hormone measurements, are being considered for inclusion in the existing models. Studies are underway to determine if these factors are feasible and will improve breast cancer risk prediction, according to the study authors.
Editorial: Models Differ in Details
"The authors have provided a useful survey of the literature and have presented an informative summary of the risk factors used in various models," write Mitchell Gail, MD, PhD, and Phuong Mai, MD, from the National Cancer Institute, in a related editorial. Drs. Gail and Phuong caution, however, that the various models differ in important details and that physicians need to be cognizant of these differences.
"Promising directions include incorporating mammographic density, information on genotype or regulation of gene expression ... and more refined use of pathology data and biomarker data from biopsy samples," the editorialists add.
Abstract: CONCLUSION: MSI was infrequent in ovarian tumors, including both borderline and malignant tumors. MSI was found to be uncommon in sporadic ovarian tumors, even by using additional MSI markers. The clinical significance of MSI is not strong in patients with sporadic ovarian tumors.
Link to full text (pdf file):
....MSI is caused by mutations in the mismatchrepair genes (MMR). MSI has been implicated in the pathogenesis of colon, endometrial, and gastric
carcinomas that occur in the setting of HNPCC (Lynch Syndrome), and also in a subset of sporadic cancers such as upper urinary tract, stomach, colon, andendometrial carcinomas.
In ovarian cancers, the reported incidence of MSI ranges from 0 to 37%, depending on the number and type of markers. Sood et al. first
reported the incidence of MSI in ovarian cancer using the NCI criteria.....Therefore, further study of molecular events that are correlated with ovarian tumors is needed."
add your opinions cancer patients genetics breast colorectal ovarian health , Lynch Syndrome , MSI
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"JNCI Interview: Dr. Regina Ziegler discusses a large study suggesting that fruits and vegetables are associated with only a modest reduction in cancer risk."