Symposium 11: Risk Modeling and Communication. "Risk assessment vs. Risk perception: Ethical issues in communicating uncertainty", presented by Gail Geller, Johns Hopkins Medical Institutions, Baltimore, MD. "The way in which clinician-investigators and patient-subjects communicate about risk and make decisions in the face of probablistic information is influenced by how they understand and respond to uncertainty. Tolerance for uncertainty in clinical practice and research will become increasingly important, particularly in the area of genetic susceptibility testing. Although new technologies will provide more opportunities for prediction, many tests will leave residual uncertainties regarding future disease. The way that physicians interpret such probabilistic information will determine the accuracy of the information they transmit to patients and the enthusiasm with which they recommend genetic testing. Similarly, the way that patients interpret the information that is provided to them will affect their well-being and their willingness to undergo genetic testing." Issues: Distinction between risk assessment and risk uncertainty. Differences in perception of risk and perception of the uncertainties associated with genetic susceptibility testing among families at increased risk for cancer. Miscommunication of risk on the part of the media and misunderstanding of risk on the part of the general population. Ethical implications of risk communication, including the potential for overstatement of benefit, understatement of harm and coercion. Ann's NOTE: For the last month or so I have been thinking about prophylactic mastectomy. This is a subject I feel strongly about. After all, due to a cancer diagnosis, I had both breasts removed. I might not have had the second mastectomy if I had known there was no invasive cancer in that breast - the ultimate diagnosis was Stage 0, non-invasive cancer (Paget's Disease of the Nipple). When a woman goes for genetic counseling, as per presentations/discussions at various conferences including the Era of Hope (DoD Breast Cancer Research, 9/02), she receives information about prophylactic mastectomy. This is usually done within a cancer/medical center. Genetic counselors are trained not to recommend but to inform (this is based on their original work with pregnant women and possibly 'damaged' fetuses where extreme caution is needed when 'counseling'. This non directive style has carried over. Except that, when a woman is told or made to feel at high risk, there is no permanent decision NOT to do something. Since she remains at the same or higher risk (as she ages), she can always revisit the option to DO something. There are no recommendations made for support groups for high risk women, although that now seems like a good idea. Women are presented with the 'facts' of prophylactic mastectomy and left to think it over. Those of us who have followed the 'science' of genetic risks for (breast) cancer, have seen the changes in what we know and how it could affect decisions. The 'choice' of surgery is often due the fact that we have appallingly poor methods of 'following' someone's circumstances. If a woman is at high risk due to family history, and is young (under 45), a mammogram is unlikely to be helpful, yet some of these women have had them year after year. Ultrasound is not fully reliable, MRI is expensive and often not covered by insurance, and so it goes. Yet the prophylactic surgery option always exists. During a presentation at the Era of Hope, I noticed that the concept of the sexual nature of the breast was NOT mentioned at all, either on the pro side or the con side. When I pointed this out, many women in the audience applauded. I know from other conferences that the sexual nature of our breast is purposely left out as too controversial, possibly insulting or embarrassing. But where can we exchange accurate information. I think it is possible that some women may undergo prophylactic mastectomy (and mastectomy for disease) without fully understanding that loss of existing breasts most likely will include loss of feeling in the area. So the surgical option hangs over these women, year after year. A surgical option for colon cancer protection includes a colectomy. I am not 100% sure what is involved, but I doubt I would like it. "Uses and abuses of the "Gail" model for projecting absolute breast cancer risk", presented by Mitchell H. Gail, NCI, Bethesda, MD. "The "Gail" model projects the absolute risk, namely the probability, of developing breast cancer over a defined time period for women with given breast cancer risk factors. Absolute risk depends on age at the beginning of the interval, the duration of the interval, risk factors for breast cancer, and the risk of dying from other causes before breast cancer develops." "Another potential use of an absolute risk model is too discriminate women who will develop breast cancer from those who will not. But a well calibrated model may not have sufficient discriminatory power to reliably determine which women will develop breast cancer." Ann's NOTE: I attended another symposium, so did not hear Dr. Gail this time around. However, it is obvious that his "Gail" model will be unlikely to discriminate women who are diagnosed with 'random' or non-familial breast cancer. He stated he was going to "mention caveats and exceptions". There are many. Symposium 12: Minorities and Medically Underserved Populations in Cancer Prevention. "Estrogen receptor negative breast cancer", presented by Worta Mccaskill-Stevens, NCI, Bethesda, MD. "One-third of the newly diagnosed cases of breast cancer are estrogen receptor negative (ERN)." "Approximately 40% of breast cancers among African American women are estrogen receptor negative." Younger women have higher rates of ERN breast cancer and incidence rates of younger African American women exceed those for Caucasian women. On the average African American women are diagnosed at earlier ages." "Chemoprevention clinical trials of estrogen receptor positive breast cancer have shown a 70% reduction in the (relative) risk of invasive breast cancer with the use of tamoxifen with no reduction in ERN breast cancers. Developments in genomics and proteomics suggest that distinct categories of breast cancer exist and originate from luminal cells of the breast epithelium and basal or basal like epithelial cells." Ann's NOTE: Vitamin A used as a treatment against chest wall tumor (recurrence) was able to make a less than 30% positive ER and PR (progesterone receptor) change to 90% positive for both. In discussions with several noted oncologists and researchers, all agreed that indeed vitamin A could have this effect. Yet it is NEVER offered for this purpose. Perhaps studies need to be done to convince the decision-makers to try it. If some know about it, why is it not discussed? "Polymorphisms in the androgen receptor may predispose prostate cancer in African-American men", presented by Douglas K. Price, NCI, Bethesda, MD. "Survival rates, both general and stage-specific, for men with prostate cancer are poorer for African-American than either Caucasian or Asian-American patients. Presenting with late stage prostate cancer may be explained by reduced access to health care, but does not explain the differences in stage-specific survival." This paper goes on to discuss possible genetic polymorphisms (or changes) that may account for these differences. The author suggests an area his group has been studying may be of account-CAG repeat. "There is an inverse relationship between CAG length and AR transactivation function (i.e. The shorter the CAG, the better the R is at activating gene transcription) has lead to a hypothesis that the racial differences seen in prostate cancer susceptibility may be due in part to the variability in the AR CAG repeat length." "To build on these findings we are currently analyzing the AR CAG repeat length of selected patients representing all races taking part in the Southwest Oncology Group sponsored Prostate Cancer Prevention Trial (N=18,000)." Symposium 13: Prevention of Lung and Aerodigestive Cancers and Barrett's Esophagus. "Natural history of premalignant bronchial lesions: Implications for chemoprevention", presented by Stephen Lam, British Columbia Cancer Agency, Vancouver, BC, Canada. "The cumulative lifetime risk for lung cancer in smokers is less than 20%. To develop and apply an effective chemoprevention strategy, it is important to have the means to identify the minority of smokers who would truly benefit from the intervention. It is also important to define the target lesions to be reverted or prevented from developing. The outcome of 2611 volunteer smokers > 45 years of age with a smoking history of >20 pack-years who participated in several NCI sponsored chemoprevention trials was determined from their clinical follow up and from the Cancer Registry. The mean age of the participants was 58 years. Forty percent of them were women. The mean duration of follow up was 4.7 years. Computer-assisted image analysis of sputum cells obtained by induction was performed in all and 56% were found to have sputum atypia on image analysis. Autofluorescence bronchoscopy, chest x-ray/spiral CT was performed in 1011 subjects with sputum atypia. Seventeen subjects were found to have lung cancer. Four of them had CT occult carcinoma in situ (CIS) found by autofluorescence bronchoscopy. The tumors in the remaining 13 subjects detected by CT were in areas beyond the range of a 6-mm bronchoscope." "We conclude from our study that sputum atypia by image analysis may identify subjects at high risk of developing lung cancer. A combination of spiral CT and autofluorescence bronchoscopy examination is required to find both central and peripheral carcinomas. Bronchial dysplasia is a useful target lesion for evaluation of new chemopreventive agents because it is both a pre-malignant lesion and a marker for the presence of other pre-malignant lesions elsewhere in the bronchial tree. The time to progression to CIS/invasive cancer from lesser histologies may be very short. An effective chemopreventive regimen should therefore prevent both appearance of new dysplastic lesions and eradicate existing high-grade dysplastic lesions." "Emerging molecular tools in clinical prevention studies", presented by Li Mao, UT M.D. Anderson Cancer Center, Houston, TX. "The tumorigenic process in epithelial cancers is multistep and requires accumulation of multiple genetic and epigenetic alterations." "In the upper aerodigestive tract including oral, larynx/pharynx, and lung, tobacco smoke is the common cause of tumorigenesis and damages a large area of the airway known as field defect, which not only increases incidence of cancer development but also the development of second primary tumors. The identification and determination of molecular alterations in the early tumorigenesis extend our understanding of underlying biology of the epithelial cancers and provide molecular markers for cancer risk assessment and early detection." "In a recent study, we used the method (mRNA in-situ hybridization) to determine the expression status of hTERT, the catalytic unit of human telomerase, in specimens from the bronchial tree of heavy smokers before and after treatment with 4-HPR (vitamin A analog) or placebo. Over 60% of biopsy specimens expressed hTERT mRNA in both groups at baseline level. Interestingly, after 6 months of treatment, the frequency of hTERT expression was significantly reduced in the biopsy specimens obtained from the 4-HPR-treated group but not the placebo-treated group suggesting a novel mechanism may underlie the potential chemopreventive properties of 4-HPR." "Molecular predictors of progression to cancer in Barrett's Esophagus", presented by Brian J. Reid, Fred Hutchinson Cancer Research Center, Seattle, WA. "Barrett's Esophagus (BE) is the only known precursor of esophageal adenocarcinoma (EA) but most patients with BE do not progress to cancer during follow up. Presently histological classification of dysplasia is used for risk stratification in BE, but the existing dysplasia classification is poorly reproducible and variably predictive of progression to cancer. Therefore, there is a clinical need for molecular predictors of progression for risk stratification in patients with BE. Further BE constitutes an excellent model of human epithelial neoplastic progression because serial biopsies can be taken over time to determine the temporal evolution of neoplastic cell lineages in humans in vivo." "Molecular markers of clonal changes in BE have great promise in predicting progression to EA." Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. 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