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PubMed2003

The role of estrogens in BRCA1/2 mutation carriers: reflections on the past, issues for the future.

Persons undergoing genetic testing for an inherited predisposition to cancer often raise questions about recommendations for follow-up care. Missing from current guidelines is consideration of the role of estrogens for BRCA1/BRCA2 mutation carriers. Potential implications of hormones for risk of cancer and effectiveness of risk-reduction strategies need to be considered in the design of comprehensive guidelines for high-risk women. Patients who are mutation carriers may ask questions about the use of oral contraceptives, hormone replacement, and utility of current screening modalities. Controversy exists, even when considering these issues for the general population, but become more imperative when considering young, unaffected women who carry an inherited genetic mutation making decisions that may have long-term health consequences. Many patients have considered estrogen ablation via prophylactic surgeries as risk-reduction interventions. This article reviews data regarding these issues, makes recommendations based on available information, and offers future perspectives for those identified at high risk for cancer because of genetic predisposition. Although questions remain regarding the potential implications of hormones for risk of cancer and effectiveness of risk-reduction strategies, all information should be considered when educating and caring for such patients.

Breast Neoplasms↗

PubMed1986

Managing the cancer risk in chronic ulcerative colitis. A decision-analytic approach.

Chronic ulcerative colitis is associated with a high risk of colon cancer. The most appropriate management--prophylactic proctocolectomy or medical surveillance--is, at present, unclear. Recent reports suggest that the presence of colonic dysplasia or "precancer" on endoscopic biopsy may be a reliable predictor of concurrent or future colon cancer. To assess the value of colonic dysplasia in managing colitis patients, I applied decision analytic techniques to currently available data regarding the sensitivity and specificity of colonic dysplasia in colitis patients. Such analysis shows that management based on biopsy for colonic dysplasia, rather than prophylactic proctocolectomy for all colitis patients, will maximize 5-year survival. Sensitivity analysis suggests that management is primarily determined by the sensitivity of biopsy-diagnosed dysplasia--elective prophylactic surgery would be preferred only when sensitivity of dysplasia on biopsy is less than or equal to 0.70 at 20 years, or less than or equal to 0.85 at 30 years of colitis, and changing surgical mortality and survival benefit from early diagnosis within a range established by previous studies affects management decisions only when sensitivity of dysplasia is at the lower end of its reported range.

Biopsy↗

PubMed1998

Spontaneous shrinkage of lumbosacral lipoma in conjunction with a general decrease in body fat: case report.

OBJECTIVE AND IMPORTANCE: We describe a rare case of a lumbosacral lipoma that shrank spontaneously in parallel to a general loss of body fat. Although early prophylactic surgery is generally recommended for lumbosacral lipomas, the observation made in this case may provide an important implication regarding the conservative management of this disorder. CLINICAL PRESENTATION: A 9-year-old male patient with a subcutaneous lipoma at the sacral level was found to have a lumbosacral lipoma in the spinal canal and tethered spinal cord, as revealed by magnetic resonance imaging. The patient showed no neurological or urological deficits, except for a mild pes cavus deformity. INTERVENTION: Follow-up magnetic resonance imaging performed 4 years later revealed a significant decrease in the size of the lumbosacral lipoma. The patient became very thin and showed no neurological deterioration during the follow-up period. The shrinkage of the lipoma was considered to be in association with the general loss of body fat. CONCLUSION: The control of body weight may be an important factor in the conservative management of patients with lumbosacral spinal lipomas.

Child↗

PubMed1979

Skin abnormalities of the back in diastematomyelia.

The presence of congenital skin abnormalities on the back may be associated with a serious underlying spinal anomaly, diastematomyelia. The significance of the progressive development of neurological deficits, due to the presence of a bony or cartilaginous spur in the spinal cord, is stressed. An awareness of this condition should lead to an early diagnosis with a neurological evaluation and, if necessary, prophylactic surgery before irreversible nerve damage develops.

Adolescent↗

PubMed2005

Use of intensified early cancer detection in high-risk patients with familial breast and ovarian cancer.

A prospective follow-up study was carried out to evaluate the influence of risk and genetic counselling on use of early cancer detection. Five hundred and fifty-six subjects who fulfilled inclusion criteria for a genetic analysis of the BRCA1/2 genes (the high-risk group A) and 205 who did not fulfil the inclusion criteria (the lower risk group B) attended primary consultation in the interdisciplinary cancer genetic clinic. Information about participation in the early cancer detection programme was documented. Information about changes in use after consultation could be evaluated from 349 women (94 group B and 255 group A). Methods such as monthly self-palpation, breast palpation by gynaecologist, ultrasound of the breast, transvaginal ultrasound and pelvic examination had all been commonly used. Consultees at higher risk used mammography less often than women at lower risk. Magnetic resonance imaging of the breast was used rarely. Most methods were used more often at the recommended interval by women at higher risk during the follow-up period. In conclusion, at present intensified early cancer detection programmes for women at risk provide a less invasive option than chemoprevention or prophylactic surgery. Although the methods are used at high frequency it seems feasible to motivate women at risk to participate. This can be done by providing information and counselling in the cancer genetic clinic.

Adult↗

PubMed1999

Toxicity of NSAIDs in the stomach and duodenum.

NSAIDs are widely used for analgesic, anti-inflammatory and anti-thrombotic indications. Such use carries the risk of gastrointestinal complications (1% over 6 months) which NSAIDs may promote from both ulcerous and nonulcerous lesions. Symptoms are poor predictors of serious lesions and complications, which may occur without previous symptoms. NSAIDs also delay healing of peptic ulcers, even to the extent of intractability, and may cause recurrence after gastric surgery. Prophylactic therapy is indicated in high-risk patients (age > 60 years, previous ulcer history, high dose, concomitant use of corticosteroids or anticoagulants). Misoprostol, omeprazole and high-dose famotidine have been shown to reduce the occurrence of both gastric and duodenal ulcers in NSAID users. At present, the role of Helicobacter pylori in NSAID-induced gastroduodenal lesions is controversial and there is no agreement in considering the organism as a risk factor and indicating its eradication in NSAID users.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2002

Genetics competency: new directions for nursing.

Imagine nurses caring for several patients. One uses genetic testing results to decide about prophylactic surgery to reduce cancer risks. The second nurse modifies dietary habits on the basis of a genetic test result and prevents long-term effects from impaired metabolism of the amino acid phenylalanine. The third nurse cares for a patient who recovers from a narcotic overdose after a gene alteration that affects drug metabolism. Due to the significant advances of the Human Genome Project and related genetics research, clinical applications of genetic technology are moving into nursing practice. Resources are available to help nurses meet this challenge. The National Coalition for Health Professional Education in Genetics has issued a set of competencies that mandates new directions for nursing education and practice. To ensure that patients understand both the promise and the limitations of genetic discovery, it is imperative to ensure the competence of critical care nurses.

Competency-Based Education↗

PubMedDate not supplied

No news is (not necessarily) good news: impact of preliminary results for BRCA1 mutation searches.

PURPOSE: Many women who have had breast or ovarian cancer who are undergoing tests for the presence of germline mutations in the genes will receive a result that is inconclusive. As this continuing uncertainty may have a detrimental effect on their psychological well-being and it is possible that such results will be misinterpreted as indicating that no mutation is present, studying their effect is important. METHODS: Sixty-one women undergoing such tests completed questionnaires 2 weeks after their blood was taken and at 1 week and 6 months after receiving a preliminary "inconclusive" result, i.e., indicating that two thirds of the gene had been tested and no mutation had been found so far. RESULTS: Perceived likelihood of having a mutation and perceptions of cancer risk significantly decreased after receipt of the interim result. There were no changes in levels of psychological distress and worry about cancer, in intentions to have mammograms, to carry out breast self-examination, or to have prophylactic surgery. CONCLUSIONS: The continuing uncertainty does not seem to have increased distress; however, it is possible that the inconclusive result is being interpreted as a "good news" result, in view of the fact that perceptions of risk decrease after receipt of the result.

Adult↗

PubMed2003

Rating the risk factors for breast cancer.

OBJECTIVE: To update and summarize evidence of risk factors for breast cancer. SUMMARY BACKGROUND DATA: Women who are at high risk for breast cancer have a variety of options available to them, including watchful waiting, prophylactic surgery, and chemoprevention. It is increasingly important to accurately assess a patient's risk profile to ensure that the cost/benefit ratio of the selected treatment is favorable. METHODS: Estimates of relative risk for documented risk factors were obtained from seminal papers identified in previous reviews. These estimates were updated where appropriate with data from more recent reports using large sample sizes or presenting meta-analyses of previous studies. These reports were identified from a review of the Medline database from 1992 to 2002. RESULTS: Risk factors that have received a great deal of publicity (hormone use, alcohol consumption, obesity, nulliparity) present a relatively modest relative risk for breast cancer (<2). Factors associated with a prior history of neoplastic disease or atypical hyperplasia and factors associated with a genetic predisposition significantly affect the risk of breast cancer, with relative risks ranging from 3 (for some cases of positive family history) to 200 (for premenopausal women positive for a BRCA mutation). CONCLUSIONS: More precise tools, based on techniques of molecular biology such as microarray analysis, will be needed to assess individual risk for breast cancer.

Alcohol Drinking↗

PubMedDate not supplied

Breast cancer risk assessment and prevention: a framework for shared decision-making consultations.

Options for breast cancer prevention, used in combination with screening and surveillance, include lifestyle modifications, chemoprevention with tamoxifen, and prophylactic surgery. Preventive health decisions are often preference driven: patients typically must choose whether to initiate effective treatments that hold the possibility of side effects that can negatively impact quality of life. This situation demands that patients be well informed and have a full understanding of the risks associated with each option. Investigators have developed a comprehensive decision-making framework designed to support breast cancer prevention consultations within a shared decision-making setting. The framework integrates predictive information from current risk models within the context of a woman's general health to appropriately frame breast cancer risk management consultations and outlines the application of available treatments and emerging biomarker information to individual patient decisions. Using an evidence-based approach, specialized risk-benefit projections can be provided in the clinical setting. A more comprehensive individualized risk profile allows for tailored medical management plans and can better prepare patients to make informed decisions. The framework is intended to encourage a shared decision-making approach to prevention consultations, a method for researchers to increase accrual to trials, and to more quickly incorporate new findings into the routine of practice.

Age Factors↗

PubMed2005

'Indirect' BRCA1/2 testing: a useful approach in hereditary breast and ovarian cancer families without a living affected relative.

We report an approach for BRCA1/2 testing whereby genetic testing can be offered to families at high risk of hereditary breast and ovarian cancer but where no DNA from affected relatives is available. By testing two or more unaffected relatives at 50% risk of being heterozygous for a potential BRCA1/2 mutation, there is a chance of up to 99% of finding a mutation that would have been detectable in an affected individual from the same family. The overall likelihood of identifying a mutation is dependent on the family history, and therefore 'indirect' testing would be most applicable for families with a very high risk of carrying a BRCA1/2 mutation. Using this approach also requires balancing issues of testing resource limitations, family dynamics and adequate preparation of unaffected persons for a positive test, with the advantages of targeting screening and prophylactic surgery.

Adult↗

PubMed2006

A gift or a yoke? Women's and men's responses to genetic risk information from BRCA1 and BRCA2 testing.

This qualitative study explored the impact of genetic risk information from BRCA1/2 testing on individuals' subjective understandings of self and self-identity. In-depth interviews were conducted with 39 participants (34 women and 5 men) who had received test results from BRCA1/2 testing. Themes emerging from qualitative data analysis revealed that participants linked their positive results to becoming more aware of their physical selves (embodied self), their selves in relation to family (familial-relational self) and their selves in relation to wider kinship or social groups (social self). Genetic information was generally viewed as enabling; it allowed participants to take measures (surveillance or prophylactic surgery) to confront the disease. However, for a small minority of women, knowledge about their genetic risk had a profound and limiting effect on their agency. Rather than giving them a sense of control, they saw little opportunity to fight the disease. For a few people, identification of a genetic mutation thrust them into an uncertain state, that is in a position of being neither ill nor completely well. In one case, BRCA information led to a disruption of social identity. Further work is needed to assess the impact of age and life stage on psychological responses to genetic information on cancer susceptibility.

Adult↗

PubMed2006

EFNS Guidelines on diagnosis and treatment of brain metastases: report of an EFNS Task Force.

The objectives have been to establish evidence-based guidelines and identify controversies regarding the management of patients with brain metastases. The collection of scientific data was obtained by consulting the Cochrane Library, bibliographic databases, overview papers and previous guidelines from scientific societies and organizations. A tissue diagnosis is necessary when the primary tumor is unknown or the aspect on computed tomography/magnetic resonance imaging is atypical. Dexamethasone is the corticosteroid of choice for cerebral edema. Anticonvulsants should not be prescribed prophylactically. Surgery should be considered in patients with up to three brain metastases, being effective in prolonging survival when the systemic disease is absent/controlled and the performance status is high. Stereotactic radiosurgery should be considered in patients with metastases of 3-3.5 cm of maximum diameter. Whole-brain radiotherapy (WBRT) after surgery or radiosurgery is debated: in case of absent/controlled systemic cancer and Karnofsky Performance score of 70 or more, one can either withhold initial WBRT or deliver early WBRT with conventional fractionation to avoid late neurotoxicity. WBRT alone is the treatment of choice for patients with single or multiple brain metastases not amenable to surgery or radiosurgery. Chemotherapy may be the initial treatment for patients with brain metastases from chemosensitive tumors.

Advisory Committees↗

PubMedDate not supplied

The founder mutation BRCA1c.2845insA identified in a fallopian tube cancer patient: a case report.

Fallopian tube carcinoma is a very rare tumor, comprising less than 1% of all gynecologic cancers and found primarily in postmenopausal women. With the disease being so uncommon, little is known about its causes and/or risk factors, and treatment approaches have been taken from experiences with ovarian cancer. We describe a case of a 42-year-old woman with fallopian tube cancer in which the founder mutation BRCA1c.2845insA was detected by mutational analysis. This same mutation was subsequently detected in four unaffected members of her family following genetic counseling. We report an association between this founder mutation and fallopian tube cancer as part of the hereditary breast cancer syndrome in an Asian population. A literature review of the association between this rare malignancy and BRCA mutation carriers and its implications to prophylactic surgery is discussed.

Adenocarcinoma, Papillary↗

PubMedDate not supplied

Efficacy of screening women at high risk of hereditary ovarian cancer: results of an 11-year cohort study.

The outcome of screening and prophylactic surgery in 269 women at high risk of hereditary ovarian cancer is reported. Screening was performed using transvaginal ultrasound and serum CA125 testing. Mean follow-up was 26 months (583 person-years). A total of 113 (42%) of 269 women had a pathogenic BRCA1 or BRCA2 mutation, and 127 (47%) of 269 women underwent salpingo-oophorectomy. No occult cancers were found. In eight women having both elevated CA125 levels and abnormal ultrasound findings, a malignancy was found. Four of these cancers (one borderline, one stage Ia, one stage IIIb, and one stage IIIc ovarian or peritoneal cancer) were detected at the first screening visit. One stage IIIb and one stage IIIc cancer were detected at the second screening visit after 12 months, and two interval stage IIIc and IV cancers were detected 8 and 10 months after the first screening visit. No peritoneal carcinoma was found among those 114 women who underwent bilateral salpingo-oophorectomy with normal or benign pathology results, after a mean follow-up of 16 months (152 person-years). We conclude that the efficacy of screening women at high risk of ovarian cancer seems poor because the majority of cancers were detected at an advanced stage.

Adult↗

PubMed1996

Florid oral manifestations in an atypical familial adenomatous polyposis family with late presentation of colorectal polyps.

Early identification and prophylactic surgery are essential in preventing development of malignancy in colorectal polyps in familial adenomatous polyposis (FAP). Previous studies indicate a 100% cumulative risk of developing colonic polyps in individuals with FAP by the age of 34 yr. However, we have previously reported late-onset and non-penetrance of polyposis in four families. We describe here in detail one of these families with florid oral manifestations detectable on panoramic radiography of the jaws, which were instrumental in the diagnosis of FAP in the index patient and for ascertainment of her family for screening. The pathological adenomatous polyposis coli (APC) gene mutation in this family was shown to segregate with dento-osseous changes. Panoramic jaw radiography is a common examination carried out prior to dental or oral surgical procedures. This case illustrates the importance of appropriate investigations, including family history and colonoscopy, even in relatively older patients with radiological findings such as those described here and in members of their families at risk of FAP.

Adenomatous Polyposis Coli↗

PubMed1983

Upper gastrointestinal tract polyps in familial adenomatosis coli.

Upper gastrointestinal tract polyps were sought prospectively using endoscopy and biopsy in 34 patients with familial adenomatosis coli belonging to 18 unrelated families. Gastric and/or duodenal polyps, usually small and multiple, occurred in 28 patients (82%). Histologically verified extracolonic adenomas were present in 19 patients (56%). Gastric adenomas, all in the antrum, and duodenal adenomas occurred in four (12%) and 16 (48%) patients, respectively. In one patient, a duodenal adenocarcinoma and a bile duct adenoma were also found, and one patient had an adenocarcinoma of the bile ducts. Multiple non-neoplastic polyps were found in 19 patients (56%), most often in the stomach and also in the duodenum in 12 patients; they co-existed often with adenomas. In addition, there were nine patients with ileal polyps, most of them showing lymphoid hyperplasia but also one with adenomas. It is suggested that familial adenomatosis affects the whole gastrointestinal tract, not only the colon and rectum as believed earlier. Although upper gastrointestinal tract adenomas are not as consistent and multiple as those in the colon, and probably do not require prophylactic surgery, regular lifelong endoscopic follow up is warranted because of obviously increased cancer risk.

Adolescent↗

PubMed1992

Overview of screening and management of familial adenomatous polyposis.

The rarity of familial adenomatous polyposis (FAP) means that many clinicians may be unaware of the major advances that have taken place in screening for the condition over the past five years. This review is not only to document the current scene but also to give details of those involved in establishing registries throughout the country. FAP is a hereditary disorder which carries with it almost a 100% risk of colorectal cancer. The aim of screening is to detect gene carriers before they present with symptoms attributable to colonic polyps. In this way the incidence of colorectal cancer can be greatly reduced. The use of gene probes to identify patients with FAP is in its infancy but in selected pedigrees gene carriers can be identified using a venous blood sample. The recognition that congenital hypertrophy of the retinal pigment epithelium is an extracolonic manifestation of FAP in most pedigrees allows non-invasive ophthalmological screening of relatives at risk. The combination of these new screening methods with an effective regional registry for FAP can increase the number of patients detected by screening rather than by symptoms. This facilitates appropriate prophylactic surgery and reduces mortality related to colorectal cancer.

Adenomatous Polyposis Coli↗