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Biomedical subjects

J Brisson

Publications and source records attributed to J Brisson.

At least 19 recordsLinked to original sources
PubMed2005

The benefit of participating to clinical research.

We assessed the impact of participating to clinical research among 1727 women with localized breast cancer. Using as referent individuals not treated according to guidelines for systemic therapy, the adjusted hazard ratio of death was 0.70 (95% confidence interval (CI): 0.54,0.90, p-value: 0.006) in those treated according to current guidelines and 0.45 (95% CI: 0.27,0.73, p-value: 0.001) in participants to research. Participation to clinical trials results in a substantial gain in survival.

Biomedical Research↗
PubMed2003

Contribution of clinical breast examination to mammography screening in the early detection of breast cancer.

OBJECTIVES: As the benefit of clinical breast examination (CBE) over that of screening mammography alone in reducing breast cancer mortality is uncertain, it is informative to monitor its contribution to interim measures of effectiveness of a screening programme. Here, the contribution of CBE to screening mammography in the early detection of breast cancer was evaluated. SETTING: Four Canadian organised breast cancer screening programmes. METHODS: Women aged 50-69 receiving dual screening (CBE and mammography) (n = 300,303) between 1996 and 1998 were followed up between screen and diagnosis. Outcomes assessed by mode of detection (CBE alone, mammography alone, or both CBE and mammography) included referral rate, positive predictive value, pathological features of tumours (size, nodal status, morphology), and cancer detection rates overall and for small cancers (< or = 10 mm or node-negative). Heterogeneity in findings across programmes was also assessed. RESULTS: On first versus subsequent screen, CBE alone resulted in 28.5-36.7% of referrals, and 4.6-5.9% of cancers compared with 52.6-60.1% of referrals and 60.0-64.3% of cancers for mammography alone. Among cancers detected by CBE, 83.6-88.6% were also detected by mammography, whereas for mammographically detected cancers only 31.7-37.2% were also detected by CBE. On average, CBE increased the rate of detection of small invasive cancers by 2-6% over rates if mammography was the sole detection method. Without CBE, programmes would be missing three cancers for every 10,000 screens and 3-10 small invasive cancers in every 100,000 screens. CONCLUSIONS: Inclusion of CBE in an organised programme contributes minimally to early detection.

Breast Neoplasms↗
PubMed2002

Delay in adjuvant radiation treatment and outcomes of breast cancer--a review.

Recent meta-analyses have shown the importance of locoregional control as a long-term determinant of breast cancer survival. Whether factors related to the delivery of radiotherapy, such as delay, dose, fractionation or irradiated volume, are associated with outcome remains unclear. We performed a critical review of the literature on delay to radiation using a computerized search of papers published between 1985 and 2000. Periods of accrual, details of radiotherapy, surgical and systemic treatment, and information on prognostic factors were noted. Studies on sequencing of adjuvant therapy were compared to studies on delay to radiation, classified according to whether or not patients also received chemotherapy. Comparisons of patients receiving systemic therapy to individuals spared this option were considered uninformative since the impact of delaying radiation is then highly confounded by systemic treatment received. The single published experimental study on sequencing suggests that delay to radiation may compromise local control, and this is consistent with a few retrospective reports on delay to radiotherapy among patients receiving chemotherapy. However, indirect evidence from two randomized clinical trials of chemotherapy, and the majority of observational studies on delay to radiotherapy, suggest that it has no impact on either local, distant control or survival. Factors, methodological, and others, that could explain these inconsistencies are discussed. No study restricted to patients at low risk of recurrence suggested an impact of delaying radiation. Short chemotherapy regimens are likely to represent a safe option with respect to outcome of radiation treatment.

Adult↗
PubMed2001

Expression of cathepsin D, stromelysin-3, and urokinase by reactive stromal cells on breast carcinoma prognosis.

BACKGROUND: Current literature suggests that several proteases act in a cascade to mediate remodeling of the extracellular matrix and favor cancer progression. Others and the authors of this study recently identified cathepsin D, stromelysin-3, and urokinase plasminogen activator (uPA) expression by reactive stromal cells as significant factors of poor prognosis in breast carcinoma. The authors evaluated the joint effect of protease expression on cancer aggressiveness. METHODS: Protease expression was analyzed by immunohistochemistry (cathepsin D) and in situ hybridization (stromelysin-3 and uPA) on formalin fixed paraffin embedded specimens from 557 breast carcinomas without distant metastasis at diagnosis and with an average of 10 years of follow-up. RESULTS: Of the 557 breast carcinomas, 80 (14.3%) expressed all 3 proteases, and 134 (24%) expressed none of them. An adjusted Cox model revealed significantly worse distant metastasis free survival (DMFS) with expression of all three proteases (P < 0.0001). The DMFS of patients whose tumor lacked at least one of the three proteases was similar to that of patients without any protease expression, irrespective of the type or number of proteases missing. CONCLUSIONS: This study suggests that proteases expressed by reactive stromal cells are interdependent and that a breach in the protease pathway may impair breast carcinoma progression.

Breast Neoplasms↗
PubMed2001

Short polyglutamine tracts in the androgen receptor are protective against breast cancer in the general population.

We studied the association of breast cancer with the polymorphic polyglutamine repeat of the androgen receptor (AR) in 255 incident cases of breast cancer and 461 matched controls from the Quebec City metropolitan area. Women for whom the sum of both of the AR (CAG)n-repeats alleles is 39 or less (short-allele AR genotypes) have one-half the risk of breast cancer compared with women for whom the sum of AR (CAG)n-repeats is 40 or more [odds ratio (OR), 0.5; 95% confidence interval (CI), 0.3-0.83; P = 0.007]. This association is stronger in postmenopausal women (180 cases, 297 controls; OR, 0.36; 95% CI, 0.19-0.7; P = 0.003). We also observed an interaction between the type of menopause (natural versus surgical) and the AR genotype on breast cancer risk. Alternately, when subjects were grouped according to their (CAG)n-repeat genotype [homozygous for short alleles (CAG)n < or = 20; other genotypes ("long allele")], results were similar (OR. 0.5; 95% CI, 0.27-0.82; P = 0.007). Thus, women with short-alleles AR genotypes appear to be protected against breast cancer. Short-alleles AR genotypes were observed in 16% of the general population as represented by the control group. Short polyglutamine repeats in the AR protein have been reported to be associated with an increase in the capacity of the receptor to activate transcription of reporter genes in vitro. Furthermore, androgens have been previously shown to inhibit in vitro the growth of breast cancer cell lines. This suggests that differences in the number of polyglutamines in the AR protein may influence individual risk of breast cancer, especially in postmenopausal women, and that this apparent protection could be the consequence of an increased response/sensitivity to androgens.

Breast Neoplasms↗
PubMed2001

Disrupting evolutionary processes: the effect of habitat fragmentation on collared lizards in the Missouri Ozarks.

Humans affect biodiversity at the genetic, species, community, and ecosystem levels. This impact on genetic diversity is critical, because genetic diversity is the raw material of evolutionary change, including adaptation and speciation. Two forces affecting genetic variation are genetic drift (which decreases genetic variation within but increases genetic differentiation among local populations) and gene flow (which increases variation within but decreases differentiation among local populations). Humans activities often augment drift and diminish gene flow for many species, which reduces genetic variation in local populations and prevents the spread of adaptive complexes outside their population of origin, thereby disrupting adaptive processes both locally and globally within a species. These impacts are illustrated with collared lizards (Crotaphytus collaris) in the Missouri Ozarks. Forest fire suppression has reduced habitat and disrupted gene flow in this lizard, thereby altering the balance toward drift and away from gene flow. This balance can be restored by managed landscape burns. Some have argued that, although human-induced fragmentation disrupts adaptation, it will also ultimately produce new species through founder effects. However, population genetic theory and experiments predict that most fragmentation events caused by human activities will facilitate not speciation, but local extinction. Founder events have played an important role in the macroevolution of certain groups, but only when ecological opportunities are expanding rather than contracting. The general impact of human activities on genetic diversity disrupts or diminishes the capacity for adaptation, speciation, and macroevolutionary change. This impact will ultimately diminish biodiversity at all levels.

Adaptation, Physiological↗
PubMed2001

Phosphorus removal from trout farm effluents by constructed wetlands.

Freshwater trout farms need a high and continuous clean water flow to keep fish exposed to a non-toxic ammonium concentration. As a result, the concentration of effluents from these farms are even below standard effluent criteria for municipal wastewater effluent for solids, nitrogen and phosphorus. Nevertheless, the mass of pollutants discharged, originating mostly from excreta and undigested fish food, must be reduced by simple and economical treatment processes. We designed and operated a three-stage system aimed at retaining solids by a 60 pm nylon rotating microscreen followed by treatment with a phosphorus-retaining constructed wetland system. Washwater from the microscreen was pumped to a series of two horizontal flow beds of 100 m3 each (0.6 m deep). Coarse (2 mm) and finer (< 2 mm) crushed limestone were used in each bed, respectively, with the first one being planted with reeds (Phragmites australis) and the second one designed to remove even more phosphorus by adsorption and precipitation. Preliminary results indicated that the microscreen captured about 60% of the suspended solids and that greater than 95% of the suspended solids and greater than 80% of the total phosphorus mass loads were retained by the beds. The potential of constructed wetlands as an ecologically attractive and economical method for treating fish farm effluents to reduce solids and phosphorus discharge appears promising.

Animals↗
PubMed2000

Rectal cancer and occupational risk factors: a hypothesis-generating, exposure-based case-control study.

In 1979, a hypothesis-generating, population-based case-control study was undertaken in Montreal, Canada, to explore the association between occupational exposure to 294 substances, 130 occupations and industries, and various cancers. Interviews were carried out with 3, 630 histologically confirmed cancer cases, of whom 257 had rectal cancer, and with 533 population controls, to obtain detailed job history and data on potential confounders. The job history of each subject was evaluated by a team of chemists and hygienists and translated into occupational exposures. Logistic regression analyses adjusted for age, education, cigarette smoking, beer consumption, body mass index, and respondent status were performed using population controls and cancer controls, e.g., 1,295 subjects with cancers at sites other than the rectum, lung, colon, rectosigmoid junction, small intestine, and peritoneum. We present here the results based on cancer controls. The following substances showed some association with rectal cancer: rubber dust, rubber pyrolysis products, cotton dust, wool fibers, rayon fibers, a group of solvents (carbon tetrachloride, methylene chloride, trichloroethylene, acetone, aliphatic ketones, aliphatic esters, toluene, styrene), polychloroprene, glass fibers, formaldehyde, extenders, and ionizing radiation. The independent effect of many of these substances could not be disentangled as many were highly correlated with each other.

Adult↗
PubMed2000

Structure of the Bordetella pertussis 1414 endotoxin.

The endotoxin (lipopolysaccharide) of Bordetella pertussis, the agent of whooping cough, consists of a lipid A linked to a highly branched dodecasaccharide containing several acid and amino sugars. The elucidation of the polysaccharide structure was accomplished by first analyzing the structures of fragments obtained by hydrolysis and nitrous deamination and then piecing the fragments together. The fine structure of the antigenic distal pentasaccharide, presented here, was determined by chemical analyses as well as by high-resolution nuclear magnetic resonance and mass spectrometry. The complete structure was reconstituted and confirmed by matrix-assisted laser desorption/ionization mass spectrometry. The following structure was derived from the combined experimental data:The detailed structure combined with previously reported serological data now allows the synthesis of its epitopes for potential vaccines.

Amination↗
PubMed2000

Human papillomaviruses and vulvar vestibulitis.

OBJECTIVE: To assess the relationship between human papillomavirus (HPV) infection and vulvar vestibulitis syndrome. METHODS: From November 1995 to December 1997, 135 women with vulvar vestibulitis were compared with 322 controls who had no evidence of vulvar vestibulitis. Human papillomavirus DNA was amplified by polymerase chain reaction and detected with liquid-capture molecular assay. RESULTS: Human papillomavirus DNA was found in 29.6% of cases and in 23.9% of controls (relative risk [RR] 1.4; 95% confidence interval [CI].8, 2.2). The prevalence of HPV tended to decrease with increasing duration of pain among cases. Thus, prevalences were 37. 5%, 29.6%, and 22.0% for pain durations of 3-6 months, 7-12 months, and 13-24 months, respectively (P =.14). Prevalence of HPV also tended to increase with pain intensity among cases, but that association was not statistically significant (P =.57). Prevalence percentages for women with low, moderate, or severe pain were 27.5%, 28.8%, and 34.4%, respectively. Prevalence of HPV was slightly higher in cases with the most severe pain (34.4%) than in controls (23.9%) (RR 1.8; 95% CI.8, 4.0). In cases with the most pain in the shortest time (3-6 months), prevalence of HPV was double that of controls (50% versus 23.9%) (RR 3.5; 95% CI 1.0, 12.7; P =.054). CONCLUSION: There was little support for the idea that HPV might be related to vulvar vestibulitis.

Adult↗
PubMed2000

Risk and aggressiveness of breast cancer in relation to plasma organochlorine concentrations.

Several organochlorines identified as "hormone mimics" were proposed as possible risk factors for breast cancer. We conducted a case-control study to assess breast cancer risk and disease aggressiveness in relation to plasma concentrations of several organochlorine compounds. Plasma lipid concentrations of 11 chlorinated pesticides and 14 polychlorinated biphenyl congeners were measured in 315 women newly diagnosed with breast cancer, 219 hospital-based controls, and 307 population controls from the Quebec City area (Canada). Concentrations of hormonally active organochlorines or their surrogates were compared between cases and controls as well as between groups of cases defined according to tumor size and axillary-lymph-node involvement. We found similar levels of organochlorines in cases and controls and no relationship between the relative risk of breast cancer and organochlorine exposure. However, the probability of lymph-node invasion among cases increased with exposure to 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene [p,p'-DDE; odds ratio, 2.54; 95% confidence interval (CI), 1.20-5.35; between the highest and the lowest tertiles]. Furthermore, p,p'-DDE exposure was associated with a dose-related increased relative risk of exhibiting both lymph-node involvement and a large tumor. Indeed odds ratio raised to 2.33 (95% CI, 0.94-5.77) for the second tertile relative to the first tertile and reached 3.51 (95% CI, 1.41-8.73) for the third tertile relative to the first tertile. Similar associations were noted with beta-hexachlorocyclohexane, oxychlordane, and transnonachlor. We conclude that exposure to persistent, hormonally active organochlorines during adulthood is not associated with breast cancer risk. The possibility that some organochlorines and especially p,p'-DDE may increase breast cancer aggressiveness deserves further attention.

Adult↗
PubMed2000

Tamoxifen and mammographic breast densities.

The extent of breast tissue density on mammograms is one of the strongest risk factors for breast cancer. The aim of this analysis was to evaluate whether tamoxifen can affect mammographic breast density. Subjects were participants in the National Surgical Adjuvant Breast Project Breast Cancer Prevention Trial (BCPT), recruited and followed at the Breast Center of Saint-Sacrement Hospital in Quebec City, Canada. The Breast Cancer Prevention Trial is a double-blind trial in which women at high risk of breast cancer were randomized to receive either 20 mg tamoxifen per day or placebo. Mammograms were taken before treatment began and yearly thereafter. For the purpose of this analysis, Wolfe's parenchymal pattern and the percentage of the breast showing tissue densities were assessed by review of pre- and posttreatment mammograms without knowledge of treatment assignment. Among the 69 women included in this analysis, 36 received tamoxifen and 33 received placebo for an average of 3.3 and 3.5 years, respectively. Among women receiving tamoxifen, 16 of 36 (44.4%) changed to a parenchymal pattern of lower density compared with 5 of 33 (15.2%) women receiving placebo (P = 0.010). Moreover, in the tamoxifen-treated group, the difference in the percentage of the breast showing tissue densities between the pre- and posttreatment mammograms reached -9.4% on average compared with a reduction of -3.6% in the placebo group (P = 0.010). Our data show that tamoxifen can reduce high-risk mammographic features. Breast densities should be evaluated as possible early markers of the preventive effect of selective estrogen receptor modulators.

Adult↗
PubMed1999

Variations in the treatment of early-stage breast cancer in Quebec between 1988 and 1994.

BACKGROUND: The influence of organizational factors on the process and outcomes of the treatment of breast cancer has been extensively investigated. Although the quality of care is presumed to be better in larger centres, evidence is inconsistent. This study was conducted to determine whether therapies for patients with breast cancer varied according to hospital caseload. METHODS: Women newly diagnosed between 1988 and 1994 with early-stage node-negative primary breast cancer were randomly selected from the Quebec tumour registry and the Quebec hospital discharge database. Data were collected from medical charts, and only women having undergone dissection of the axilla were included in the analyses. Logistic regression analysis was used to adjust for case mix and organizational variables. RESULTS: The final sample included 1259 patients with node-negative stage I or II primary breast cancer. The proportion of women who underwent breast-conserving surgery increased significantly with hospital caseload (from 78.0% in hospitals admitting fewer than 25 new cases each year to 88.0% in those admitting 100 patients or more; p for trend < 0.001). This trend remained significant even after statistical adjustment for case mix and organizational factors (p for trend = 0.001). Of the 1039 women who underwent breast-conserving surgery 965 (92.9%) received radiotherapy. Use of systemic adjuvant therapy (tamoxifen or chemotherapy, or both) increased with the number of patients treated in a given centre (from 60.1% to 68.5%), but this trend disappeared after adjustment for case mix and other factors. The proportion of patients receiving systemic adjuvant therapy consistent with published consensus guidelines tended to increase with caseload for those treated in hospitals participating in multicentre clinical trials but decrease with caseload for patients in hospitals not involved in clinical research. INTERPRETATION: The care of patients in Quebec with early-stage breast cancer is characterized by a high prevalence of both breast-conserving surgery and systemic adjuvant therapy. Large centres, especially those actively involved in clinical research, rapidly adopt innovative therapeutic modalities.

Breast Neoplasms↗
PubMed1999

A structural comparison of the total polar lipids from the human archaea Methanobrevibacter smithii and Methanosphaera stadtmanae and its relevance to the adjuvant activities of their liposomes.

Mice were immunized with bovine serum albumin (BSA) entrapped within archaeosomes (i.e. liposomes) composed of the total polar lipids (TPL) from the two methanogenic archaea common to the human digestive tract. Methanobrevibacter smithii archaeosomes boosted serum anti-BSA antibody to titers comparable to those achieved with Freund's adjuvant, whereas Methanosphaera stadtmanae archaeosomes were relatively poor adjuvants. An explanation for this difference was sought by analysis of the polar lipid composition of each archaeobacterium. Fast atom bombardment mass spectrometry and NMR analyses of the purified lipids revealed a remarkable similarity in the ether lipid structures present in each TPL extract. However, the relative amounts of each lipid species varied dramatically. The phospholipid fraction in M. stadtmanae TPL was dominated by archaetidylinositol (50 mol% of TPL) and the glycolipid fraction by beta-Glcp-(1,6)-beta-Glcp-(1,1)-archaeol (36 mol%), whereas in M. smithii extracts, both caldarchaeol and archaeol lipids containing a phosphoserine head group were relatively abundant. Liposomes prepared from purified archaetidylinositol and from M. stadtmanae TPL supplemented with increasing amounts of phosphatidylserine elicited poor humoral responses to encapsulated BSA. A dramatic loss in the adjuvanticity of M. smithii archaeosomes was seen upon incorporation of 36 mol% of the uncharged lipid diglucosyl archaeol and, to a lesser extent, of 50 mol% of archaetidylinositol. Interestingly, the relative rates of uptake of M. smithii and M. stadtmanae archaeosomes by phagocytic cultures in vitro were similar. Thus, the lipid composition may influence archaeosome adjuvanticity, particularly a high diglucosyl archaeol and/or archaetidyl inositol content, resulting in a low adjuvant activity.

Adjuvants, Immunologic↗
PubMed1999

Compliance with consensus recommendations for the treatment of early stage breast carcinoma in elderly women.

BACKGROUND: The goal of this study was to assess variations with age in the management of breast carcinoma and to identify determinants of care received. METHODS: A stratified random sample was selected among women age > or = 50 newly diagnosed with lymph node negative breast carcinoma in Quebec in 1988, 1991, and 1993. Information was abstracted from medical charts. Predictors of definitive locoregional treatment (total mastectomy with lymph node dissection or breast-conserving surgery with both axillary lymph node dissection and radiation therapy) were identified by multiple logistic regression analysis. RESULTS: Overall, 1174 patients age > or = 50 years with breast carcinoma were included. Women age > or = 70 years were much less likely to receive definitive locoregional treatment compared with women ages 50-69 years (48.7% vs. 83.5%; P < 0.0001). Older women were less likely to undergo surgery with breast preservation (76.7% vs. 86.3%; P < 0.0001), radiation therapy (54.7% vs. 90.5%; P < 0.0001), dissection of the axillary lymph nodes (55.6% vs. 86.3%; P < 0.0001), or chemotherapy (1.2% vs. 13.9%; P < 0.0001), but not treatment with tamoxifen (66.4% vs. 64.7%; P = 0.41). Adjusting for comorbidity and other characteristics related to the disease, the hospital, and the attending physician, age remained a strong determinant of the probability of receiving definitive locoregional treatment (odds ratio [OR], 0.14; 95% confidence interval [95% CI], 0.12-0.18 for women age > or = 70 years vs. women ages 50-69 years). The same association was observed when women who did not undergo lymph node dissection but who received systemic adjuvant treatment were considered to have received definitive therapy (OR, 0.13; 95% CI, 0.10-0.17) for women age > or = 70 years vs. women ages 50-69 years). CONCLUSIONS: Less aggressive patterns of care are provided to elderly breast carcinoma patients, independent of comorbidity. This could explain, at least in part, the sustained breast carcinoma mortality in this population.

Age Factors↗
PubMed1999

Cathepsin D expression by cancer and stromal cells in breast cancer: an immunohistochemical study of 1348 cases.

This study was aimed at investigating the influence of cathepsin D (CD) expression by cancer cells and stromal cells on breast cancer prognosis. This is a study of 1348 node-positive (NPBC) and node-negative (NNBC) breast cancers diagnosed between 1980 and 1986 and with a minimum follow-up of 5.2 years. CD expression was assessed by immunohistochemistry on archival material using a polyclonal antibody. The expression by cancer and stromal cells was assessed separately and correlated with distant metastasis free (DMFS) and overall survival (OS). Cancer cells expressed CD (more than 10% cells expressing CD) in 38.9% of cases and reactive stromal cells in 43.6%. CD expression by reactive stromal cells, and not cancer cells, correlated with several factors of poor prognosis by cancer cells. A strong association was also found with expression of other proteases (stromelysin-3, gelatinase A, and urokinase Plasminogen Activator) by these same reactive stromal cells. CD expression by cancer cells did not predict DMFS or OS but, by univariate analysis, CD expression by reactive stromal cells was associated with earlier recurrence and shorter survival in NNBC (p = 0.0425) and NPBC patients submitted to adjuvant chemotherapy (p = 0.0234). However, CD expression by reactive stromal cells remained a significant predictor of recurrence by multivariate analyses only in a subgroup of NPBC submitted to adjuvant chemotherapy. Overall, those data support the concept that proteases produced by reactive stromal cells are under cancer cell stimulation and that CD by stromal cells, and not cancer cells, influences the prognosis, but only in a subgroup of patients with breast cancer.

Adenocarcinoma↗
PubMed1999

Conservation and accessibility of an inner core lipopolysaccharide epitope of Neisseria meningitidis.

We investigated the conservation and antibody accessibility of inner core epitopes of Neisseria meningitidis lipopolysaccharide (LPS) because of their potential as vaccine candidates. An immunoglobulin G3 murine monoclonal antibody (MAb), designated MAb B5, was obtained by immunizing mice with a galE mutant of N. meningitidis H44/76 (B. 15.P1.7,16 immunotype L3). We have shown that MAb B5 can bind to the core LPS of wild-type encapsulated MC58 (B.15.P1.7,16 immunotype L3) organisms in vitro and ex vivo. An inner core structure recognized by MAb B5 is conserved and accessible in 26 of 34 (76%) of group B and 78 of 112 (70%) of groups A, C, W, X, Y, and Z strains. N. meningitidis strains which possess this epitope are immunotypes in which phosphoethanolamine (PEtn) is linked to the 3-position of the beta-chain heptose (HepII) of the inner core. In contrast, N. meningitidis strains lacking reactivity with MAb B5 have an alternative core structure in which PEtn is linked to an exocyclic position (i.e., position 6 or 7) of HepII (immunotypes L2, L4, and L6) or is absent (immunotype L5). We conclude that MAb B5 defines one or more of the major inner core glycoforms of N. meningitidis LPS. These findings support the possibility that immunogens capable of eliciting functional antibodies specific to inner core structures could be the basis of a vaccine against invasive infections caused by N. meningitidis.

Animals↗