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A gene-expression signature as a predictor of survival in breast cancer. A more accurate means of prognostication in breast cancer will improve the selection of patients for adjuvant systemic therapy.Using microarray analysis to evaluate our previously established 70-gene prognosis profile, we classified a series of 295 consecutive patients with primary breast carcinomas as having a gene-expression signature associated with either a poor prognosis or a good prognosis. All patients had stage I (...) or II breast cancer and were younger than 53 years old; 151 had lymph-node-negative disease, and 144 had lymph-node-positive disease. We evaluated the predictive power of the prognosis profile using univariable and multivariable statistical analyses.Among the 295 patients, 180 had a poor-prognosis signature and 115 had a good-prognosis signature, and the mean (+/-SE) overall 10-year survival rates were 54.6+/-4.4 percent and 94.5+/-2.6 percent, respectively. At 10 years, the probability of remaining
clinical detection. One study provides good evidence that radical prostatectomy reduces disease-specific mortality for men with localized prostate cancer detected clinically. No study has examined the additional benefit of earlier treatment after detection by screening. Men with a life expectancy of fewer than 10 years are unlikely to benefit from screening even under favorable assumptions. Each treatment is associated with several well-documented potential harms.Although potential harms of screening (...) Screening for prostate cancer: an update of the evidence for the U.S. Preventive Services Task Force. In U.S. men, prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer death. Screening for prostate cancer is controversial.To examine for the U.S. Preventive Services Task Force the evidence of benefits and harms of screening and earlier treatment.MEDLINE and the Cochrane Library, experts, and bibliographies of reviews.Researchers developed eight questions
registries in the Surveillance, Epidemiology, and End Results (SEER) program.12 038 women who were Medicare beneficiaries, were at least 69 years of age, resided in a SEER area, and received a new diagnosis of breast cancer in 1995 through 1996.Screening mammograms obtained in the 2 years before breast cancer diagnosis (none, one, or at least two) and stage and size of tumor at diagnosis.Older women (> or =75 years of age) had larger tumors at diagnosis and were less likely to have undergone screening (...) mammography than younger women (69 to 74 years of age). The association between increased mammography use and smaller tumor size and stage was significantly greater in older women than in younger women (P = 0.010 for stage; P = 0.001 for size). The percentage of regular mammography users who received a diagnosis of high-stage disease (28% vs. 26%; P > 0.2) and the mean size of the tumors (15.0 mm vs. 15.1 mm; P > 0.2) did not significantly differ between younger and older women, respectively
Use of postmenopausal hormones, alcohol, and risk for invasive breast cancer. Physiologic evidence suggests that use of alcohol increases the risk for breast cancer through a hormonal mechanism, but the relationship among breast cancer, alcohol, and postmenopausal hormones (PMH) remains unclear.To examine the relation between concurrent use of alcohol and PMH and invasive breast cancer.Prospective cohort studyNurses' Health Study.44 187 postmenopausal women.Self-reported data on PMH use (...) and breast cancer obtained from biennial questionnaires completed from 1980 to 1994 and average alcohol consumption in 1980, 1984, 1986, and 1990.1722 women developed invasive breast cancer. Risk for breast cancer was elevated in women who currently used PMH for 5 or more years and did not drink alcohol (relative risk, 1.32 [95% CI, 1.05 to 1.66]) and those who never used PMH but drank 20 or more g (1.5 to 2 drinks) of alcohol daily (relative risk, 1.28 [CI, 0.97 to 1.69]). Current users of PMH for 5
Specific localisation of human cytomegalovirus nucleic acids and proteins in human colorectal cancer. Colorectal cancer is the second most frequent cause of death from cancer in the USA, and most tumours arise sporadically with no clear cause or genetic predisposition. Human cytomegalovirus is a beta-herpesvirus that is endemic in the human population and can cause life-threatening disease in immunosuppressed adults. In vitro, human cytomegalovirus can transform cells and dysregulate many (...) , we used immunohistochemistry with two different monoclonal antibodies, in-situ hybridisation, and PCR with DNA sequencing.Human cytomegalovirus proteins IE1-72 and pp65 were detected in a tumour cell-specific pattern in 14 (82%) of 17 and seven (78%) of nine colorectal polyps, respectively, and 12 (80%) of 15 and 11 (92%) of 12 adenocarcinomas, respectively, but not in adjacent non-neoplastic colon biopsy samples from the same patients (none of seven and none of two, respectively). Human
oesophagus can be categorised according to the predominant cancer hallmark affected. For example, M Auvinen and colleagues recently observed abnormalities in the expression of vascular endothelial growth factors (VEGFs) in Barrett's oesophagus (J Clin Oncol 2002; 20: 2971-79). These abnormalities can be categorised as those that affect angiogenesis, a process that is essential for the development and progression of tumours. WHERE NEXT? The cancer hallmarks of Barrett's oesophagus provide a framework (...) Hallmarks of cancer progression in Barrett's oesophagus. Hanahan and Weinberg proposed in 200 that carcinogenesis involves DNA changes that enable cells to:provide their own growth signals, ignore growth-inhibitory signals, avoid apoptosis, replicate without limit, sustain angiogenesis, and invade and proliferate in unnatural locations. The metaplastic cells of Barrett's oesophagus are predisposed to develop these cancer hallmarks.The genetic changes that have been described in Barrett's
. Immunohistochemical assessments of cyclin E were also made of 256 tumors. We sought correlations between levels of these molecular markers and disease-specific and overall survival.The median follow-up was 6.4 years. A high level of the low-molecular-weight isoforms of cyclin E, as detected by Western blotting, correlated strongly with disease-specific survival whether axillary lymph nodes were negative or positive for metastases (P<0.001). Among 114 patients with stage I breast cancer, none of the 102 patients (...) Cyclin E and survival in patients with breast cancer. Cyclin E, a regulator of the cell cycle, affects the behavior of breast-cancer cells. We investigated whether levels of cyclin E in the tumor correlated with survival among patients with breast cancer.Tumor tissue from 395 patients with breast cancer was assayed for cyclin E, cyclin D1, cyclin D3, and the HER-2/neu oncogene with the use of Western blot analysis. Full-length, low-molecular-weight, and total cyclin E were measured
Dying of lung cancer or cardiac failure: prospective qualitative interview study of patients and their carers in the community. To compare the illness trajectories, needs, and service use of patients with cancer and those with advanced non-malignant disease.Qualitative interviews every three months for up to one year with patients, their carers, and key professional carers. Two multidisciplinary focus groups.Community based.20 patients with inoperable lung cancer and 20 patients with advanced (...) coordinated.Care for people with advanced progressive illnesses is currently prioritised by diagnosis rather than need. End of life care for patients with advanced cardiac failure and other non-malignantdiseases should be proactive and designed to meet their specific needs.
Accumulation of mitochondrial DNA mutations in ageing, cancer, and mitochondrial disease: is there a common mechanism? In man, cells accumulate somatic mutations of mitochondrial DNA (mtDNA) as part of normal ageing. Although the overall concentration of mutant mtDNA is low in tissue as a whole, very high numbers of various mtDNA mutations develop in individual cells within the same person, which causes age-associated mitochondrial dysfunction. Some tumours contain high numbers of mtDNA (...) mutations that are not present in healthy tissues from the same individual. The proportion of mutant mtDNA also rises in patients with progressive neurological disease due to inherited mtDNA mutations. This increase parallels the relentless clinical progression seen in these disorders. Mathematical models suggest that the same basic cellular mechanisms are responsible for the amplification of mutant mtDNA in ageing, in tumours, and in mtDNA disease. The accumulation of cells that contain high levels
Breast cancer in men. Breast cancer in men is uncommon; 1500 new cases are diagnosed in the United States yearly. Optimal management of breast cancer in men is unknown because the rarity of the disease precludes large randomized trials. A review of the literature was undertaken with emphasis on articles published over a 10-year period.Articles published between 1942 and 2000 on breast cancer in men were identified by using CancerLit, MEDLINE, and study bibliographies.All retrospective series (...) and studies focusing on the epidemiology, risk factors, genetics, and pathology of breast cancer in men.Data on the epidemiology, risk factors, genetics, pathology, molecular markers, prognostic factors, therapy, and outcomes of breast cancer in men.Carcinoma of the male breast accounts for 0.8% of all breast cancers. Risk factors include testicular disease, benign breast conditions, age, Jewish ancestry, family history, and the Klinefelter syndrome. BRCA2 mutations predispose men to breast cancer and may
corresponding estimates by cohort-based survival analysis. By period analysis, 20-year relative survival rates were close to 90% for thyroid and testis cancer, exceeded 80% for melanomas and prostate cancer, were about 80% for endometrial cancer, and almost 70% for bladder cancer and Hodgkin's disease. A 20-year relative survival rate of 65% was estimated for breast cancer, of 60% for cervical cancer, and of about 50% for colorectal, ovarian, and renal cancer.Timely detection of improvements in long-term (...) Long-term survival rates of cancer patients achieved by the end of the 20th century: a period analysis. Long-term survival rates for many types of cancer have substantially improved in past decades because of advances in early detection and treatment. However, much of this improvement is only seen many years later with traditional cohort-based methods of survival analysis. I aimed to assess achievements in cancer patients' survival by an alternative method of survival analysis,known as period
Why men with prostate cancer want wider access to prostate specific antigen testing: qualitative study. To explore the attitudes of men with confirmed or suspected prostate cancer to testing for prostate specific antigen.Qualitative interview study with a purposive sample.Great Britain.52 men with suspected or confirmed prostate cancer, recruited through general practitioners, urologists, patient support groups, and charities.Almost all men remembered their prostate specific antigen test (...) but recalled being given little information beforehand. Arguments in favour of increased access to testing included the belief that early diagnosis would reduce mortality, improve quality of life, and save the NHS money. Men also thought that a national screening programme should be available because symptoms can be ambiguous, screening for cancer is responsible health behaviour, and screening would encourage men to be tested. Four men who opposed a screening programme had gathered information alerting
Natural experiment examining impact of aggressive screening and treatment on prostate cancer mortality in two fixed cohorts from Seattle area and Connecticut. To determine whether the more intensive screening and treatment for prostate cancer in the Seattle-Puget Sound area in 1987-90 led to lower mortality from prostate cancer than in Connecticut.Natural experiment comparing two fixed cohorts from 1987 to 1997.Seattle-Puget Sound and Connecticut surveillance, epidemiology, and end results (...) areas.Population based cohorts of male Medicare beneficiaries aged 65-79 drawn from the Seattle (n=94 900) and Connecticut (n=120 621) areas.Rates of screening for prostate cancer, treatment with radical prostatectomy and external beam radiotherapy, and prostate cancer specific mortality.The prostate specific antigen testing rate in Seattle was 5.39 (95% confidence interval 4.76 to 6.11) times that of Connecticut, and the prostate biopsy rate was 2.20 (1.81 to 2.68) times that of Connecticut during 1987-90
Carcinogenic and endocrine disrupting effects of cigarette smoke and risk of breast cancer. Results of epidemiological studies, assessing the relation between smoking and breast cancer, have been inconclusive. Our aim was to assess the carcinogenic and possibly antioestrogenic effects of cigarette smoke on risk of breast cancer.We sent a questionnaire to 1431 women younger than age 75 years who had breast cancer and were listed on the population-based British Columbia cancer registry between (...) June 1, 1988, and June 30, 1989. We also sent questionnaires to 1502 age-matched controls, randomly selected from the 1989 provincial voters list. We obtained information on all known and suspected risk factors for breast cancer, and on lifetime smoking, alcohol consumption, and occupational history. We assessed the effect of smoking separately for premenopausal and postmenopausal women, adjusting for confounding variables.318 premenopausal women and 340 controls replied. Risk of breast cancer
articles; 208 of these were deemed to be potentially eligible and were retrieved for detailed data extraction. Sixty-five primary studies were analyzed, including 26 346 women.Data were abstracted on characteristics and quality from each study. Results for diagnostic accuracy were extracted to form 2 x 2 contingency tables separately for endometrial cancer and endometrial disease (cancer, hyperplasia, or both). Pooled likelihood ratios (LRs) were used as summary accuracy measures.The pretest (...) . The overall accuracy for the diagnosis of endometrial disease was modest compared with that of cancer, and the results were heterogeneous. The accuracy tended to be higher among postmenopausal women and in the outpatient setting.The diagnostic accuracy of hysteroscopy is high for endometrial cancer, but only moderate for endometrial disease (cancer or hyperplasia).
The genetics of colorectal cancer. Colon cancer is a common disease that can be sporadic, familial, or inherited. Recent advances have contributed to the understanding of the molecular basis of these various patterns of colon cancer. Germline genetic mutations are the basis of inherited colon cancer syndromes; an accumulation of somatic mutations in a cell is the basis of sporadic colon cancer; and, in Ashkenazi Jewish persons, a mutation that was previously thought to be a polymorphism may (...) cause familial colon cancer. Mutations of three different classes of genes have been described in colon cancer etiology: oncogenes, suppressor genes, and mismatch repair genes. Knowledge of many of the specific mutations responsible for colon carcinogenesis allows an understanding of the phenotypic manifestations observed and forms the basis of genetic testing for inherited disease. Although genetic testing is possible and available, it is only an adjunct to the clinical management of persons
Risk of ovarian cancer in breast-cancer patients with a family history of breast or ovarian cancer: a population-based cohort study. Patients with breast cancer who have mutations in the high penetrance genes BRCA1 and BRCA2, have an increased risk of ovarian cancer. Because these mutations are rare, easily obtained information such as age and family history of breast or ovarian cancer might be preferable for assessment of ovarian cancer risk in clinical practice.We linked data from the Swedish (...) Cancer Register to the Swedish Generation Register and generated a cohort of 30552 breast-cancer patients born after 1931, with information on breast and ovarian cancer diagnosis from 146117 first-degree relatives. Standardised incidence ratios (SIRs) with 95% CIs were calculated with nationwide rates of ovarian cancer, adjusted for age and calendar year.During a mean follow-up of 6 years, 122 incident ovarian cancers were identified in the cohort, yielding an overall SIR of 2.0 (95% CI 1.6-2.4
Prohibitin 3' untranslated region polymorphism and breast cancer risk in Australian women. A C to T transition within the 3' untranslated region of the prohibitin gene alters mRNA function, and an association between the T allele and an increased risk of breast cancer has been reported in North American women, specifically in those aged under 50 years with a first-degree family history of breast cancer. We did a population-based case-control study to assess whether this association existed (...) in Australian women. We did not note such an association in our sample of 1446 patients and 786 controls (odds ratio 0.96, 95% CI 0.80-1.16; p=0.7), or in subgroups defined by age or family history, or both. Hence, our results do not lend support to the hypothesis that this polymorphism contributes to risk of breast cancer.
Heritability of mammographic density, a risk factor for breast cancer. Women with extensive dense breast tissue visible on a mammogram have a risk of breast cancer that is 1.8 to 6.0 times that of women of the same age with little or no density. Menopausal status, weight, and parity account for 20 to 30 percent of the age-adjusted variation in the percentage of dense tissue.We undertook two studies of twins to determine the proportion of the residual variation in the percentage of density (...) ) in Australian twins, 67 percent (95 percent confidence interval, 59 to 75) in North American twins, and 63 percent (95 percent confidence interval, 59 to 67) in all twins studied.These results show that the population variation in the percentage of dense tissue on mammography at a given age has high heritability. Because mammographic density is associated with an increased risk of breast cancer, finding the genes responsible for this phenotype could be important for understanding the causes