Breast Cancer Cases (breast + cancer_case)

Distribution by Scientific Domains
Medical Sciences79%
Life Sciences20%

Kinds of Breast Cancer Cases

  • incident breast cancer case
    		•

    Selected Abstracts

    Evaluation of Three Algorithms to Identify Incident Breast Cancer in Medicare Claims Data

    HEALTH SERVICES RESEARCH, Issue 5 2007
    Heather T. Gold
    Objective. To test the validity of three published algorithms designed to identify incident breast cancer cases using recent inpatient, outpatient, and physician insurance claims data. Data. The Surveillance, Epidemiology, and End Results (SEER) registry data linked with Medicare physician, hospital, and outpatient claims data for breast cancer cases diagnosed from 1995 to 1998 and a 5 percent control sample of Medicare beneficiaries in SEER areas. Study Design. We evaluate the sensitivity and specificity of three algorithms applied to new data compared with original reported results. Algorithms use health insurance diagnosis and procedure claims codes to classify breast cancer cases, with SEER as the reference standard. We compare algorithms by age, stage, race, and SEER region, and explore via logistic regression whether adding demographic variables improves algorithm performance. Principal Findings. The sensitivity of two of three algorithms is significantly lower when applied to newer data, compared with sensitivity calculated during algorithm development (59 and 77.4 percent versus 90 and 80.2 percent, p<.00001). Sensitivity decreases as age increases, and false negative rates are higher for cases with in situ, metastatic, and unknown stage disease compared with localized or regional breast cancer. Substantial variation also exists by SEER registry. There was potential for improvement in algorithm performance when adding age, region, and race to an indicator variable for whether the algorithm determined a subject to be a breast cancer case (p<.00001). Conclusions. Differential sensitivity of the algorithms by SEER region and age likely reflects variation in practice patterns, because the algorithms rely on administrative procedure codes. Depending on the algorithm, 3,5 percent of subjects overall are misclassified in 1998. Misclassification disproportionately affects older women and those diagnosed with in situ, metastatic, or unknown-stage disease. Algorithms should be applied cautiously to insurance claims databases to assess health care utilization outside SEER-Medicare populations because of uneven misclassification of subgroups that may be understudied already. [source]

    Contribution of BRCA1 and BRCA2 mutations to inherited ovarian cancer,

    HUMAN MUTATION, Issue 12 2007
    Susan J. Ramus
    Abstract A total of 283 epithelial ovarian cancer families from the United Kingdom (UK) and the United States (US) were screened for coding sequence changes and large genomic alterations (rearrangements and deletions) in the BRCA1 and BRCA2 genes. Deleterious BRCA1 mutations were identified in 104 families (37%) and BRCA2 mutations in 25 families (9%). Of the 104 BRCA1 mutations, 12 were large genomic alterations; thus this type of change represented 12% of all BRCA1 mutations. Six families carried a previously described exon 13 duplication, known to be a UK founder mutation. The remaining six BRCA1 genomic alterations were previously unreported and comprised five deletions and an amplification of exon 15. One of the 25 BRCA2 mutations identified was a large genomic deletion of exons 19,20. The prevalence of BRCA1/2 mutations correlated with the extent of ovarian and breast cancer in families. Of 37 families containing more than two ovarian cancer cases and at least one breast cancer case with diagnosis at less than 60 years of age, 30 (81%) had a BRCA1/2 mutation. The mutation prevalence was appreciably less in families without breast cancer; mutations were found in only 38 out of 141 families (27%) containing two ovarian cancer cases only, and in 37 out of 59 families (63%) containing three or more ovarian cancer cases. These data indicate that BRCA1 and BRCA2 are the major susceptibility genes for ovarian cancer but that other susceptibility genes may exist. Finally, it is likely that these data will be of clinical importance for individuals in families with a history of epithelial ovarian cancer, in providing accurate estimates of their disease risks. Hum Mutat 28(12), 1207,1215, 2007. © 2007 Wiley-Liss, Inc. [source]

    PEL: an unbiased method for estimating age-dependent genetic disease risk from pedigree data unselected for family history

    GENETIC EPIDEMIOLOGY, Issue 5 2009
    F. Alarcon
    Abstract Providing valid risk estimates of a genetic disease with variable age of onset is a major challenge for prevention strategies. When data are obtained from pedigrees ascertained through affected individuals, an adjustment for ascertainment bias is necessary. This article focuses on ascertainment through at least one affected and presents an estimation method based on maximum likelihood, called the Proband's phenotype exclusion likelihood or PEL for estimating age-dependent penetrance using disease status and genotypic information of family members in pedigrees unselected for family history. We studied the properties of the PEL and compared with another method, the prospective likelihood, in terms of bias and efficiency in risk estimate. For that purpose, family samples were simulated under various disease risk models and under various ascertainment patterns. We showed that, whatever the genetic model and the ascertainment scheme, the PEL provided unbiased estimates, whereas the prospective likelihood exhibited some bias in a number of situations. As an illustration, we estimated the disease risk for transthyretin amyloid neuropathy from a French sample and a Portuguese sample and for BRCA1/2 associated breast cancer from a sample ascertained on early-onset breast cancer cases. Genet. Epidemiol. 33:379,385, 2009. © 2008 Wiley-Liss, Inc. [source]

    Evaluation of Three Algorithms to Identify Incident Breast Cancer in Medicare Claims Data

    HEALTH SERVICES RESEARCH, Issue 5 2007
    Heather T. Gold
    Objective. To test the validity of three published algorithms designed to identify incident breast cancer cases using recent inpatient, outpatient, and physician insurance claims data. Data. The Surveillance, Epidemiology, and End Results (SEER) registry data linked with Medicare physician, hospital, and outpatient claims data for breast cancer cases diagnosed from 1995 to 1998 and a 5 percent control sample of Medicare beneficiaries in SEER areas. Study Design. We evaluate the sensitivity and specificity of three algorithms applied to new data compared with original reported results. Algorithms use health insurance diagnosis and procedure claims codes to classify breast cancer cases, with SEER as the reference standard. We compare algorithms by age, stage, race, and SEER region, and explore via logistic regression whether adding demographic variables improves algorithm performance. Principal Findings. The sensitivity of two of three algorithms is significantly lower when applied to newer data, compared with sensitivity calculated during algorithm development (59 and 77.4 percent versus 90 and 80.2 percent, p<.00001). Sensitivity decreases as age increases, and false negative rates are higher for cases with in situ, metastatic, and unknown stage disease compared with localized or regional breast cancer. Substantial variation also exists by SEER registry. There was potential for improvement in algorithm performance when adding age, region, and race to an indicator variable for whether the algorithm determined a subject to be a breast cancer case (p<.00001). Conclusions. Differential sensitivity of the algorithms by SEER region and age likely reflects variation in practice patterns, because the algorithms rely on administrative procedure codes. Depending on the algorithm, 3,5 percent of subjects overall are misclassified in 1998. Misclassification disproportionately affects older women and those diagnosed with in situ, metastatic, or unknown-stage disease. Algorithms should be applied cautiously to insurance claims databases to assess health care utilization outside SEER-Medicare populations because of uneven misclassification of subgroups that may be understudied already. [source]

    BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer,,

    HUMAN MUTATION, Issue 4 2004
    Jae Hong Seo
    Abstract In order to evaluate the role of BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer, 97 patients with sporadic breast cancer were analyzed for mutations in the BRCA1 and BRCA2 coding regions, by using a combination of fluorescent-conformation sensitive gel electrophoresis (F-CSGE) and direct sequencing. Fifty-five distinct sequence variants were detected, which included three pathogenic truncating mutations, 15 missense mutations, 16 polymorphisms, and 21 intronic variants. Twenty-six of these variants have never been previously reported and may be of Korean-specific origin. Two pathogenic BRCA1 mutations (c.922_924delinsT, c.5445G>A) and one pathogenic BRCA2 mutation (c.2259delT) were observed, and two of these (BRCA1 c.5445G>A and BRCA2 c.2259delT) are novel. The total prevalence of germline pathogenic mutations in BRCA1 and/or BRCA2 in Korean sporadic breast cancer is estimated to be about 3.1%. Considering that the majority of breast cancer cases are sporadic, the present study will be helpful in the evaluation of the need for the genetic screening of germline BRCA mutations in sporadic breast cancer patients. Further study using a larger sample size is required to determine the merits of genetic diagnosis and counseling in breast cancer patients. © 2004 Wiley-Liss, Inc. [source]

    Hereditary breast and ovarian cancer in Asia: genetic epidemiology of BRCA1 and BRCA2,

    HUMAN MUTATION, Issue 6 2002
    Alexander Liede
    Abstract Ethnic differences in cancer incidence and mortality result from differences in genetic and epidemiologic risk factors. Mutations in BRCA1 and BRCA2 account for a small proportion of all breast cancer cases, but for a much higher proportion of cases with a strong family history of breast or ovarian cancer. Germline mutations in BRCA1 and BRCA2 have been identified in individuals of many races and ethnic groups and the frequency of mutations varies between these groups. Some of the differences in cancer risk between populations may be the result of founder mutations in these genes. The cost and time required for mutation analysis are reduced considerably when founder mutations are identified for a specific ethnic group. The BRCA2 999del5 mutation in Iceland and three BRCA mutations in Ashkenazi Jews are well characterized. However, considerably less is known about the contribution of mutations in the BRCA1 and BRCA2 genes outside of European groups. Studies conducted on the Asian populations described here have expanded our current knowledge of genetic susceptibility and its contribution to breast and ovarian cancer rates in Asian populations. Hum Mutat 20:413,424, 2002. © 2002 Wiley-Liss, Inc. [source]

    BRCA2 gene mutations in Greek patients with familial breast cancer ,,

    HUMAN MUTATION, Issue 1 2002
    Athanasios Armakolas
    Abstract Family history is a well-recognized risk factor for the development of breast cancer. The isolation of BRCA1 and BRCA2 genes, the two major predisposing genes in familial and to early onset breast and ovarian cancer, has resulted to the identification of a large number of families with mutations in these two genes. Despite the large number of distinct mutations detected in both genes, several mutations have been found to recur in unrelated families of diverse geographical origin. We have analyzed 27 Greek patients with familial breast cancer the majority of those having one first and one second degree relatives affected and 28 patients with sporadic breast cancer for BRCA2 germline mutations. The techniques used were single-strand conformation polymorphism analysis (SSCP) followed by sequencing. Furthermore, the clinical presentation and prognosis of BRCA2 associated breast cancer cases was compared to 20 adequately matched for age and date of diagnosis (within one year) sporadic breast cancer patients. We identified three novel BRCA2 mutations (3058delA, 6024delTA, and 4147delG) in the ovarian cancer cluster region (OCCR) and one already known (2024del5) germline BRCA2 gene mutation in five different breast cancer families. The 4147delG mutation was detected in two unrelated patients. BRCA2 germline mutations were correlated with early-onset breast cancer RR=4.77 (95% CI: 0.666-34.463). Although patients with BRCA2 germline mutations did not have a distinct histological phenotype they had an improved overall survival (100% vs 65%). Our findings suggest that there is a cluster of novel mutations in exons 10 and 11 in Greek patients with familial breast cancer. These mutations appear to have a milder clinical phenotype when compared to the rest of the study group. © 2001 Wiley-Liss, Inc. [source]

    Survival in Danish patients with breast cancer and inflammatory bowel disease: A nationwide cohort study,

    INFLAMMATORY BOWEL DISEASES, Issue 4 2008
    Kirstine Kobberøe Søgaard BA
    Abstract Background: Incidences of inflammatory bowel disease (IBD) and of breast cancer have increased over the last decades. The influence of IBD on breast cancer prognosis, however, is unknown. We therefore examined the impact of IBD on treatment receipt and survival in breast cancer patients. Methods: Information on breast cancer patients (stage and treatment) diagnosed between 1980 and 2004 was sourced from the Danish Cancer Registry. Data on IBD and potential confounders were extracted from the Danish National Registry of Patients covering all Danish hospitals. Cox regression was used to compute mortality rate ratios (MRRs) among breast cancer patients with IBD, compared to their non-IBD counterparts, adjusting for age, stage, comorbidity measured by the Charlson Index, and calendar year. Results: We identified 71,148 breast cancer cases; 67 also had Crohn's disease (CD) and 216 had ulcerative colitis (UC). Patients with CD had more advanced stage and received radiotherapy less, and chemotherapy more, frequently than patients without IBD. In the adjusted analyses there was no substantial survival difference in breast cancer patients with and without IBD (MRRCD = 1.22; 95% confidence interval [CI] = 0.85,1.75; MRRUC = 1.09; 95% CI = 0.86,1.38). In a stratified analysis, chemotherapy was associated with poorer survival in patients with CD (MRRCD = 1.93; 95% CI = 1.00,3.72). Conclusions: Breast cancer patients with UC receive the same treatment and have similar survival to breast cancer without IBD. In contrast, breast cancer patients with CD are treated with radiotherapy less often. Survival of breast cancer in patients with CD treated with chemotherapy is poorer compared to survival in patients without IBD. (Inflamm Bowel Dis 2007) [source]

    Serum levels of vitamin D, PTH and calcium and breast cancer risk,a prospective nested case,control study

    INTERNATIONAL JOURNAL OF CANCER, Issue 9 2010
    Martin Almquist
    Abstract Previous studies indicate that calcium and its regulating hormones, i.e., parathyroid hormone (PTH) and vitamin D, might affect breast cancer risk. Evidence also suggests that this relationship could be influenced by menopausal status and BMI. We examined breast cancer risk related to prediagnostic serum levels of vitamin D (25OHD2 and 25OHD3), PTH and calcium using a nested case,control design within the Malmö Diet and Cancer Study. There were 764 incident breast cancer cases, and 764 controls were selected by incidence density matching, using age as the underlying time scale, matching on calendar time at inclusion, menopausal status and age at inclusion. Using logistic regression analysis, odds ratios (OR) with 95% confidence intervals were calculated for breast cancer risk in different quartiles of the analyzed factors. All analyses were adjusted for risk factors for breast cancer, and for levels of albumin, creatinine and phosphate. Analyses were repeated stratified for BMI and menopausal status, and for low vs. high levels of 25OHD3, PTH and calcium. There was a weak, nonsignificant inverse association between breast cancer risk and 25OHD3, and the OR for the 2nd, 3rd and 4th quartiles, as compared to the first, were 0.84 (0.60,1.15), 0.84 (0.60,1.17) and 0.93 (0.66,1.33). Serum calcium was positively associated with breast cancer in premenopausal women (OR for the 4th quartile = 3.10:1.33,7.22 and p for quartile trend = 0.04), and in women with BMI > 25 (OR for the 4th quartile = 1.94:1.12,3.37 and p for trend < 0.01). There was no association between baseline serum PTH and breast cancer risk. [source]

    Nonsteroidal anti-inflammatory drugs and the risk of developing breast cancer in a population-based prospective cohort study in Washington County, MD

    INTERNATIONAL JOURNAL OF CANCER, Issue 1 2007
    Lisa Gallicchio
    Abstract The objective of this study was to examine the association between nonsteroidal anti-inflammatory drug (NSAID) use and the development of breast cancer, and to assess whether this association differed by estrogen receptor (ER) subtype. Data were analyzed from 15,651 women participating in CLUE II, a cohort study initiated in 1989 in Washington County, MD. Medication data were collected at baseline in 1989 and in 1996. Incident cases of invasive breast cancer occurring from baseline to March 27, 2006 were identified through linkage of cohort participants with the Washington County Cancer Registry and the Maryland State Cancer Registry. Cox proportional hazards modeling was used to calculate the risk ratios (RR) and 95% confidence intervals (95% CI) for breast cancer associated with medication use. Among women in the CLUE II cohort, 418 invasive breast cancer cases were identified during the follow-up period. The results showed that self-reported use of NSAIDs in both 1989 and in 1996 was associated with a 50% reduction in the risk of developing invasive breast cancer compared with no NSAID use in either 1989 or 1996 (RR = 0.50; 95% CI 0.28, 0.91). The protective association between NSAID use and the risk of developing breast cancer was consistent among ER-positive and ER-negative breast cancers, although only the RR for ER-positive breast cancer was statistically significant. Overall, findings from this study indicate that NSAID use is associated with a decrease in breast cancer risk and that the reduction in risk is similar for ER-positive and ER-negative tumors. © 2007 Wiley-Liss, Inc. [source]

    MC1R common variants, CDKN2A and their association with melanoma and breast cancer risk

    INTERNATIONAL JOURNAL OF CANCER, Issue 11 2006
    Tadeusz D, bniak
    Abstract We sought to examine the association between MC1R variants and the risk of melanoma and breast cancer in Polish population. We also determined the prevalence of compound heterozygous carriers of MC1R and CDKN2A (A148T) variants. We examined 500 unselected melanoma cases, 511 consecutive invasive breast cancer patients, 800 newborns, 421 healthy adults matched for sex and age with the melanoma cases and 511 healthy women matched for sex and age with the breast cancer cases. A statistically significant association of all 4 MC1R variants with the melanoma risk was found. For the R151C variant p value was 0.000008 and odds ratio 2.9; for the V60L variant p value was 0.007 and OR 1.78; for the R160C p was 0.006 and OR 1.76; for the R163Q p was 0.015 and odds ratio 2.1. None of the compound heterozygotes were significantly over-represented among any of the melanoma cases, the highest OR (4.2) observed in patients harbouring the A148T variant in CDKN2A and the R151C variant in MC1R. Positive association was found between carrying any of the MC1R variants and (i) increased occurrence of melanoma among I degree relatives of the carriers; (ii) increased occurrence of melanoma on UV-non-exposed skin areas. We also observed a tendency of increased risk of multiple melanomas among carriers of MC1R variants. The haplotype analysis demonstrates that MC1R variants do not co-occur in cis, compound carriers have both alleles affected. We found no association with the MC1R variants and breast cancer risk. In conclusion, the results of this population-based study show herein that MC1R variants are associated with increased melanoma risk in the Polish population. The risk of disease seems to be increased additively for patients harbouring also the CDKN2A common variant A148T. © 2006 Wiley-Liss, Inc. [source]

    Education and risk of breast cancer in the Norwegian-Swedish women's lifestyle and health cohort study

    INTERNATIONAL JOURNAL OF CANCER, Issue 4 2004
    Tonje Braaten
    Abstract A positive relationship between level of education and female breast cancer risk is well supported by scientific evidence, but few previous studies could adjust for all relevant potential confounding factors. The authors' purpose was to examine how risk for breast cancer varies with level of education and to identify factors that explain this variation, using data from a prospective cohort study including 102,860 women from Norway and Sweden who responded to an extensive questionnaire in 1991/1992; 1,090 incident primary invasive breast cancer cases were revealed during follow-up, which ended in December 1999. The Cox Proportional Hazards Model was used to calculate relative risks (RR) with 95% confidence intervals (CI). Women with more than 16 years of education had a 36% increased risk compared to the lowest educated (7,9 years) (Age adjusted RR=1.36, 95% CI: 1.10, 1.68). This relationship was slightly stronger among postmenopausal (RR 1.51) than among premenopausal (RR 1.25) women. In both groups, however, the relative risk estimates turned close to unity by adjustment for parity, age at first birth, body mass index (BMI), height, age at menarche, menopausal status, use of oral contraceptives and consumption of alcohol. The overall multivariate relative risk among the highest educated women was 1.04 (95% CI 0.82,1.32). The results of our study suggest a clear positive gradient in risk for breast cancer by level of education, which can be fully explained by established breast cancer risk factors. © 2004 Wiley-Liss, Inc. [source]

    Single nucleotide polymorphisms in the XPG gene: Determination of role in DNA repair and breast cancer risk

    INTERNATIONAL JOURNAL OF CANCER, Issue 5 2003
    Rajiv Kumar
    Abstract In this study we determined the effect of single nucleotide polymorphisms in the XPG gene on DNA repair and breast cancer susceptibility. Ninety individuals, with previously studied DNA repair rate at 24 hr of 2 types of UV-specific cyclobutane pyrimidines dimers (CPDs) in skin were genotyped for XPG polymorphism at codon 1104 (exon 15 G>C; Asp > His). The repair rate of TT=C dimer was similar in both wild-type GG homozygotes and GC heterozygotes, whereas, for TT=T, dimer repair was non-significantly (Student's t -test, p = 0.34) lower in GC heterozygotes than wild-type GG homozygotes. Genotyping of 220 breast cancer cases and 308 controls for the same single nucleotide polymorphism in exon 15 of the XPG gene exhibited marginally significant increased frequency of the variant allele (,2 3.84, p = 0.05; OR 1.33, 95% CI 1.0,1.8) in cases (C-allele 0.29) compared to controls (C-allele 0.24). Combined heterozygote and variant homozygote genotype frequency was also higher in cases than controls (,2 4.79, p = 0.03; OR 1.50, 95%CI 1.04,2.16). © 2002 Wiley-Liss, Inc. [source]

    Safety and efficacy of the combination of trastuzumab with docetaxel for HER2-positive women with advanced breast cancer.

    INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2004
    A review of the existing clinical trials, results of the expanded access programme in the UK
    Summary Trastuzumab is a humanised monoclonal antibody against the extracellular domain of HER2 (human epidermal growth factor receptor-2) that is overexpressed in about 25% of human breast cancers. It has shown clinical benefit in HER2-positive breast cancer cases when used alone or in combination with chemotherapy. Trastuzumab increases the response rate to chemotherapy and prolongs survival when used in combination with taxanes. In this article, we review the clinical trials where trastuzumab has been administered together with docetaxel, and we present the results of the trastuzumab expanded access programme (EAP) in the UK. Combination of trastuzumab with docetaxel results in similar response rates and time-to-progression with the trastuzumab/paclitaxel combinations. The toxicity of the combination and the risk of heart failure are low. The clinical data for the docetaxel/trastuzumab combination indicate a favourable profile from both the efficacy and the safety point of view and confirm the feasibility and safety of trastuzumab administration both as monotherapy and in combination with docetaxel. [source]

    Serum antioxidant and cholesterol levels in patients with different types of cancer

    JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 6 2001
    Clifford Abiaka
    Abstract Serum antioxidant (urate, ,-tocopherol) activity and cholesterol concentration in 142 patients of Indian and Arab (Kuwaitis and other Arabs) origin with different types of cancer (breast, colon, stomach, thyroid, oral, rectal, pancreatic, and renal) were compared to 100 age- and sex-matched control subjects. Values were expressed as medians (interquartile range). Urate concentration was significantly decreased in male patients compared to male controls (P < 0.0001) and in female patients and female breast cancer cases compared to female controls; P < 0.0001 and P = 0.001, respectively. ,-Tocopherol concentration decreased significantly in total cancer, stomach, colon, rectal, and breast cancer cases than the controls; P < 0.0001, P < 0.0001, P < 0.0001, P = 0.012, and P = 0.022, respectively. Cholesterol concentration decreased significantly in stomach, oral, colon, and total cancer cases compared to the controls; P < 0.0001, P < 0.0001, P = 0.002, and P = 0.012, respectively. Among controls, females had significantly (P < 0.0001) lower concentrations of ,-tocopherol than males. Among patients, cholesterol, urate, and ,-tocopherol concentrations decreased significantly in smokers than in nonsmokers; P < 0.0001, P = 0.004, and P = 0.047, respectively. Generally, changes in ,-tocopherol/cholesterol ratios mimicked changes in ,-tocopherol concentration. Concentrations of all parameters decreased significantly in male patients compared to male controls. Age was positively associated with all three analytes with respect to the controls. ,-Tocopherol correlated with cholesterol in cancer patients (r = 0.367; P < 0.0001) and with urate in the controls (r = 0.342; P < 0.0001). The data suggest cancer-related diminished synthesis of cholesterol and, generally, a greater antioxidant burden for ,-tocopherol than urate in cancer-generated oxidative stress. The increased incidence of pancreatic cancer in Kuwaitis warrants further study. J. Clin. Lab. Anal. 15:324,330, 2001. © 2001 Wiley-Liss, Inc. [source]

    Molecular genetic analysis of the BRCA2 tumor suppressor gene region in cutaneous squamous cell carcinomas

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2008
    Sarah E. Gray
    Background:, Germ line mutations of the BRCA2 tumor suppressor gene with subsequent loss of the remaining wild-type BRCA2 allele have been identified in up to 35% of familial breast cancer cases. A high frequency of allelic loss at the BRCA2 gene locus has also been reported in a variety of sporadic epithelial tumors including oesophageal squamous cell carcinomas (SCC), and sporadic head and neck SCC. Aim:, The present study aimed to examine the integrity of the BRCA2 gene in cutaneous SCC. Materials and methods:, Allelic imbalance/loss of heterozygosity (AI/LOH) was examined in 22 histologically confirmed cutaneous SCC at two microsatellite markers, D13S260 (centromeric to the BRCA2 gene) and D13S267 (telomeric to the BRCA2 gene). Immunohistochemical analysis of BRCA2 protein expression was also examined in the cutaneous SCC. Results:, AI/LOH at the D13S260 locus was found in eight of the 19 informative SCC, and AI/LOH at the D13S267 locus was found in 12 of the 18 informative SCC. Seven SCC showed allelic loss at both markers, and six SCC showed retention of heterozygosity at both markers. Expression of BRCA2 protein was only detected in six of the normal epidermises and three of the 21 SCC examined. Conclusion:, AI/LOH of the BRCA2 gene region was found to be common in the cutaneous SCC. [source]

    Radiation and breast carcinogenesis,

    PEDIATRIC BLOOD & CANCER, Issue 5 2001
    John D. Boice Jr.
    Abstract With the possible exception of radiation-induced leukemia, more is known about radiation-induced breast cancer than any other malignancy [1, 2]. Fourteen cohort studies have provided quantitative information on the level of risk following a wide range of doses in different populations around the world. Comprehensive studies have been conducted in Canada, Germany, Japan, Sweden and other Nordic countries, the United Kingdom, and the USA (Table I). Key features are the linearity in the dose response (i.e., a straight line adequately fits the observed data), and the effect modification of age at exposure (i.e., risk is inversely related to exposure age and exposures past the menopausal ages appear to carry a very low risk); and the minimal effect of fractionating dose on subsequent risk [3]. A recent combined analysis of almost 78,000 women and 1,500 breast cancer cases from eight cohorts confirmed the downturn in risk at the highest dose levels (related in part to the killing of cells rather than transformation) and that fractionation of dose has little influence on risk, at least on an absolute scale [4]. It is not known whether persons predisposed to cancer are at enhanced risk of radiation-induced breast cancer from low-dose exposures, although this seems unlikely [5]. New data on the effects of high doses following childhood exposures will be forthcoming from long-term studies of the survivors of childhood cancer (6,8). Med. Pediatr. Oncol. 36:508,513, 2001. © 2001 Wiley-Liss, Inc. [source]

    Cancer risks in thiazolidinedione users compared to other anti-diabetic agents,

    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 5 2007
    Carol Koro PhD
    Abstract Purpose We conducted three nested case-control studies to evaluate the risk of breast, colon, and prostate cancers developing in patients exposed to thiazolidinediones (TZDs) compared with other anti-diabetic agents. Methods Cancer cases were matched to five controls by age, gender, calendar year, and time in the database from a cohort of 1,26,971 diabetic patients taking anti-diabetic medication in the US Integrated Healthcare Information Services database. Five hundred thirteen breast cancer cases were matched with 2557 controls, 408 cases of colon cancer were matched with 2027 controls and 643 cases of prostate cancer were matched with 3176 controls. Exposure to an anti-diabetic agent within 90 days preceding the index date was defined as recent exposure and at any time during the follow-up was defined as ever exposed. Results The adjusted odds ratios and 95%CI of cancer from ever exposure to TZDs compared to oral monotherapy, oral dual therapy, oral triple therapy, insulin monotherapy, insulin and oral therapy and all non-TZD anti-diabetic agents were, respectively for breast cancer: 0.91 (0.69,1.20), 0.80 (0.56,1.14), 0.87 (0.32,2.35), 1.27 (0.61,2.67), 0.71 (0.36,1.37), 0.89 (0.68,1.15); for colon cancer: 1.06 (0.80,1.40), 1.12 (0.77,1.63), 1.73 (0.39,7.78), 4.46 (1.05,19.00), 1.06 (0.50,2.26) 1.03 (0.80,1.32) and for prostate cancer: 1.08 (0.85,1.37), 0.89 (0.66,1.21); 0.82 (0.33,2.06); 1.80 (0.79,4.07), 1.10 (0.55,2.18), 1.04 (0.83,1.31). Results for exposure within 90 days of the date of the cancer were similar. Conclusions Our findings suggest that the effect of TZDs on the likelihood of development of the cancers studied (colon, prostate and breast) appears to be neutral and do not support a beneficial or deleterious effect of TZD on the cancers studied. Copyright © 2006 John Wiley & Sons, Ltd. [source]

    Risk of breast cancer in association with exposure to two different groups of tricyclic antidepressants,

    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 10 2006
    Hani Tamim PhD
    Abstract Purpose In 2002, we reported an epidemiological study in which we found that some tricyclic antidepressants (identified as genotoxic in Drosophila Melanogaster) were associated with an increased risk of breast cancer, when exposure took place 11,15 years before the date of diagnosis. The implications of the results found lead us to carry out a separate case-control study, using the same source population, to validate the conclusions drawn from our previous study. Methods We accrued 7330 breast cancer cases, diagnosed between 1981 and 2000, and 29,320 controls matched on age and time. Results The association between exposure to genotoxic TCAs 11,15 years before diagnosis and the risk of breast cancer development was much weaker, as compared to what was reported in our previous study. The relative risk of breast cancer in women exposed to high doses of genotoxic TCAs 11,15 years before diagnosis was 1.17 (95%CI: 0.79,1.74), while in women exposed to high levels of non-genotoxic TCAs during the same period it was 0.95 (95%CI: 0.61,1.48). Conclusion In conclusion, we did not find supporting evidence for an increased risk of breast cancer among women exposed to TCAs up to 20 years in the past. Copyright © 2006 John Wiley & Sons, Ltd. [source]

    Occupation and breast cancer risk among Shanghai women in a population-based cohort study

    AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 2 2008
    Bu-Tian Ji MD, DrPH
    Abstract Introduction A total of 74,942 female subjects were recruited in a population-based cohort study in Shanghai, China between 1997 and 2000. We examined the relationship between occupation and breast cancer risk. Methods Cases were 586 women previously diagnosed with breast cancer at baseline and 438 women newly diagnosed with breast cancer during follow-up through December 2004. Eight controls were randomly selected for each case from cancer-free cohort members and frequency-matched to the cases by year of birth and age at diagnosis. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer risk associated with occupations, adjusting for established breast cancer risk factors. Results In the prevalent breast cancer data analysis, increased risks of breast cancer were associated with technicians in engineering/agriculture/forestry (OR,=,1.6, CI: 1.0,2.4), teaching personnel (OR,=,1.5, CI:1.1,2.0), tailoring/sewing workers (OR,=,1.6, CI:1.0,2.7), and examiners/measurers/testers (OR,=,1.5, CI:1.1,2.1) among those who started the jobs at least 20 years ago. Among incident breast cancer cases, significantly increased risks were associated with medical/health care workers (OR,=,1.4, CI:1.0,2.0), administrative clerical workers (OR,=,1.5, CI:1.0,2.4), postal/telecommunication workers (OR,=,2.2, CI:1.0,5.5), and odd-job workers (OR,=,1.7, CI:1.1,2.8) among those who started the jobs at least 20 years ago. The excess risks were found in both prevalent and incident cases for postal/telecommunication workers and purchasing/marketing personnel, although ORs reached only marginal significance. Conclusions: This study suggests that white-collar professionals and several production occupations may be associated with an increased risk of breast cancer. Am. J. Ind. Med. 51:100,110, 2008. © 2007 Wiley-Liss, Inc. [source]

    Occupation and breast cancer risk in Polish women: A population-based case-control study

    AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 2 2007
    Beata Peplonska MD
    Abstract Background The etiology of breast cancer is not well understood and the role of occupational exposures in breast carcinogenesis is still uncertain. Methods The population-based case-control study included 2,386 incident breast cancer cases diagnosed in 2000,2003, and 2,502 controls. Lifetime occupational histories and information on other potential breast cancer risk factors were obtained through personal interviews. Conditional logistic regression analyses calculated odds ratios (ORs) associated with various occupations and industries after control for potential confounders. Results We found statistically significant excesses of breast cancer among engineers (OR=2.0; 95% CI: 1.0,3.8), economists (2.1; 1.1,3.8), sales occupations-retail (1.2; 1.0,1.5), and other sales occupations (1.2; 1.0,1.5). Industries showing significantly elevated risks included special trade contractors (2.2; 1.2,4.3), electronic and electric equipment manufacturers (1.7; 1.1,2.7); and public administration/general government n.e.c. (2.7; 1.3,5.7). Each of these findings was supported by a statistically significant positive trend for duration of employment (P<0.05). A decreased breast cancer risk was observed in janitors and cleaners (0.7; 0.5,0.8). Conclusions In this study, we found few associations for breast cancer and occupations or industries. The suggestive findings for the electronic and electric equipment manufacturing industry and for the occupations with potential exposure to magnetic fields deserve further evaluation. Am. J. Ind. Med. 50:97,111, 2007. © 2006 Wiley-Liss, Inc. [source]

    Breast-Conservation Treatment Outcomes: A Community Hospital's Experience

    THE BREAST JOURNAL, Issue 1 2009
    Barbara D. Florentine MD
    Abstract:, In the United States, the majority of early breast cancer patients choose breast-conserving treatment in the community setting, yet there is a paucity of literature describing outcomes. In this paper, we describe our experience with breast-conserving treatment in a small community hospital. Our hospital tumor registry was used to identify breast cancer cases diagnosed at our hospital between 1997 and 2003. We limited our study to those women with initial attempts at breast-conserving surgery (BCS) who had follow-up oncology treatment at on-campus affiliated oncological services. We looked at factors that influence survival for early stage 0,II disease such as tumor and patient characteristics, completeness of local surgical tumor excision, and adjuvant treatment. We also evaluated the percentage of cases in which the initial BCS did not achieve adequate surgical oncological results and the number and type of subsequent surgeries that were required to achieve this goal. There were 185 cases with a median patient age of 55 and a median follow-up time of 53 months. Most tumors were stage 0,I (68%) or stage II (23%). A single surgery was deemed sufficient to achieve the desired oncological outcome in 54% of cases; the remaining cases (46%) required additional surgeries. A final margin of 5 mm or greater was successfully achieved in 81% of cases. Ninety-two percent of the patients underwent radiotherapy, 65% received hormonal therapy, and 49% underwent chemotherapy. One hundred and sixty one patients had successful breast-conserving surgeries (87%) and 24 patients (13%) ultimately required mastectomy. There were four loco-regional recurrences and 19 deaths during the study period. Our disease-free survival rate for early-stage cancer (stage 0,II) was 91% at 5 years. Our study shows that high-quality patient outcomes for breast-conserving treatment can be achieved in the community setting. [source]

    Predictors of Mastectomy in a Certified Breast Center , The Surgeon is an Independent Risk Factor

    THE BREAST JOURNAL, Issue 4 2008
    Roland Reitsamer MD
    Abstract:, The current study examined predictors of mastectomy in a certified breast center with the main impact on the factor surgeon. A total of 663 patients were analyzed for their mastectomy rates. Included were patients with T1 and T2 tumors, who had their surgery performed by one of three specialized breast surgeons with a workload of at least 50 new breast cancer cases per year. On multivariate analysis central tumor localization, positive lymph node status, nonunifocality, large tumor size, and the surgeon were independent predictors of mastectomy. Surgeon A had a mastectomy rate of 30.5% (50/164), surgeon B 26.9% (43/160) respectively, and surgeon C had a mastectomy rate of 15.8% (27/171), p = 0.005. Patients, who had surgery performed by surgeon A or surgeon B were 2.34 [95% confidence interval (CI): 1.38,3.97, p < 0.005] respectively 1.96 (95% CI: 1.14,3.36, p = 0.01) times as likely to have a mastectomy than patients who had surgery performed by surgeon C. Even in a certified breast center with specialized breast surgeons the surgeon is an independent risk factor of mastectomy, as the tumor criteria are given at the time of diagnosis. [source]

    Diagnostic Accuracy of the Gail Model in the Black Women's Health Study

    THE BREAST JOURNAL, Issue 4 2007
    Lucile L. Adams-Campbell PhD
    Abstract:, The Gail model is used to predict the risk of breast cancer in women of diverse race/ethnic groups for clinical trial protocols. However, this model has only been validated in US white women. Using a nested case-control study design, we evaluated the diagnostic accuracy of the original Gail model (GM) and that of the revised Gail model algorithm for blacks/African-Americans (GM-B) in the Black Women's Health Study (BWHS). Risk profiles were derived via a self reported questionnaire at the time of enrollment into the BWHS in 1995. Biennial questionnaires were obtained from the participants to determine the incident cases of breast cancer. The study of 725 breast cancer cases and 725 controls revealed that the 5-year risk of breast cancer based on the GM ranged from 0.2% to 15.4% among cases and 0.2% to 13.6% among the controls. Based on the GM-B, the 5-year risk of breast cancer ranged from 0.2% to 8.7% among cases and 0.2% to 7.2% among the controls. The sensitivities of the GM and GM-B model with the standard cutoff of 1.7% were 17.9% (95% CI: 15.9,19.9%) and 4.1% (95% CI: 3.0,5.2), respectively. Both the original and the modified version of the Gail model underestimate the risk of developing breast cancer in African-American women. More importantly, the modified Gail Model (GM-B) does a worse job at predicting the development of breast cancer for blacks than the original model (GM). [source]

    Expression patterns of the ATM gene in mammary tissues and their associations with breast cancer survival

    CANCER, Issue 9 2007
    Chuanzhong Ye MD
    Abstract BACKGROUND. The ataxia-telangiectasia mutated (ATM) gene plays a critical role in cell-cycle arrest, apoptosis, and DNA repair. However, to date, no study has directly investigated the association between ATM gene expression and breast cancer survival. METHODS. ATM gene expression levels were evaluated in tumor and adjacent normal tissue from patients diagnosed with primary breast cancer or BBD using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) assays. Cox regression models were used to evaluate the association of ATM gene expression and survival in a cohort of 471 breast cancer patients. RESULTS. In breast cancer cases, ATM expression in cancer tissues was decreased by approximately 50% compared with adjacent normal tissues from the same patients. In BBD cases, the expression level of the ATM gene was similar in benign tumor tissue and adjacent normal tissues. No apparent difference was found in ATM gene expression levels in adjacent normal tissues obtained from cancer patients or BBD controls. Compared with patients with the lowest tertile of the ATM mRNA, patients in the upper 2 tertiles had more favorable disease-free survival (hazard ratio [HR] = 0.46, 95% confidence interval [CI]: 0.30,0.73 and HR = 0.52, 95% CI: 0.33,0.81, respectively) and overall survival (HR = 0.56, 95% CI: 0.35,0.92 and HR = 0.70, 95% CI: 0.43,1.13, respectively). CONCLUSIONS. The ATM gene expression was down-regulated in breast cancer tissues and a high ATM gene expression level in breast cancer tissue was associated with a favorable prognosis. Cancer 2007. © 2007 American Cancer Society. [source]

    Involvement of kinesin family member 2C/mitotic centromere-associated kinesin overexpression in mammary carcinogenesis

    CANCER SCIENCE, Issue 1 2008
    Arata Shimo
    To elucidate the molecular mechanisms of mammary carcinogenesis and discover novel therapeutic targets for breast cancer, we previously carried out genome-wide expression profile analysis of 81 breast cancer cases by means of cDNA microarray coupled with laser microbeam microdissection of cancer cells. Among the dozens of transactivated genes, in the present study we focused on the functional significance of kinesin family member 2C (KIF2C)/mitotic centromere-associated kinesin (MCAK) in the growth of breast cancer cells. Northern blot and immunohistochemical analyses confirmed KIF2C/MCAK overexpression in breast cancer cells, and showed that it is expressed at undetectable levels in normal human tissues except the testis, suggesting KIF2C/MCAK to be a cancer,testis antigen. Western blot analysis using breast cancer cell lines revealed a significant increase in the endogenous KIF2C/MCAK protein level and its phosphorylation in G2/M phase. Treatment of breast cancer cells with small interfering RNA against KIF2C/MCAK effectively suppressed KIF2C/MCAK expression and inhibited the growth of the breast cancer cell lines T47D and HBC5. In addition, we found that KIF2C/MCAK expression was significantly suppressed by ectopic introduction of p53. These findings suggest that overexpression of KIF2C/MCAK might be involved in breast carcinogenesis and is a promising therapeutic target for breast cancers. (Cancer Sci 2008; 99: 62,70) [source]

    The contribution of founder mutations to early-onset breast cancer in French-Canadian women

    CLINICAL GENETICS, Issue 5 2009
    P Ghadirian
    In an ethnically-homogeneous population, it is valuable to identify founder mutations in cancer-predisposing genes. Founder mutations have been found in four breast-cancer-predisposing genes in French-Canadian breast cancer families. The frequencies of the mutant alleles have been measured neither in a large series of unselected breast cancer patients from Quebec, nor in healthy controls. These estimates are necessary to measure their contribution to the hereditary burden of breast cancer in Quebec and to help develop genetic screening policies which are appropriate for the province. We studied 564 French-Canadian women with early-onset invasive breast cancer who were treated at a single Montreal hospital. Patients had been diagnosed at age 50 or less, and were ascertained between 2004 and 2008. We screened all 564 patients for nine founder mutations: four in BRCA1, three in BRCA2 and one each in PALB2 and CHEK2. We also studied 6433 DNA samples from newborn infants from the Quebec City area to estimate the frequency of the nine variant alleles in the French-Canadian population. We identified a mutation in 36 of the 564 breast cancer cases (6.4%) and in 35 of 6443 controls (0.5%). In the breast cancer patients, the majority of mutations were in BRCA2 (54%). However, in the general population (newborn infants), the majority of mutations were in CHEK2 (54%). The odds ratio for breast cancer to age 50, given a BRCA1 mutation, was 10.1 (95% CI: 3.7,28) and given a BRCA2 mutation was 29.5 (95% CI: 12.9,67). The odds ratio for breast cancer to age 50, given a CHEK2 mutation, was 3.6 (95% CI: 1.4,9.1). One-half of the women with a mutation had a first- or second-degree relative diagnosed with breast or ovarian cancer. Thus, it can be concluded that a predisposing mutation in BRCA1, BRCA2, CHEK2 or PALB2 is present in approximately 6% of French-Canadian women with early-onset breast cancer. It is reasonable to offer screening for founder mutations to all French-Canadian women with breast cancer before age 50. The frequency of these mutations in the general population (0.5%) is too low to advocate population-based screening. [source]