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J Brisson

Publications and source records attributed to J Brisson.

At least 37 records · Page 2Linked to original sources

Time trends in systemic adjuvant treatment for node-negative breast cancer.

PURPOSE: We conducted a population-based study in Quebec, Canada, to assess longitudinal changes in systemic adjuvant therapy for node-negative breast cancer. MATERIALS AND METHODS: A stratified random sample was selected among women with newly diagnosed node-negative breast cancer in 1988, 1991, and 1993. Information on the patient, her tumor, source of care, and treatment was abstracted from medical charts. Patients were classified as being at minimal, moderate, or high risk of recurrence on the basis of criteria proposed at the 4th International Conference on Adjuvant Therapy of Primary Breast Cancer (St. Gallen, Switzerland, 1992), and systemic adjuvant treatment received was dichotomized as being consistent or not consistent with consensus recommendations. RESULTS: Overall, 1,578 cases of invasive breast carcinoma were reviewed. The proportion of patients who were given hormonal or cytotoxic treatment increased from 51.7% to 73.1% from 1988 to 1993. Virtually all women at minimal risk were treated in 1991 and 1993 according to the consensus statement. The proportions of women so treated were 75.0% and 65.4% in the moderate- and high-risk categories, respectively, in 1991. In 1993, these proportions were 71.4% and 67.0%, respectively. Omission of chemotherapy, especially in high-risk women with estrogen receptor-negative tumors who were 50 to 69 years of age, was the most frequent inconsistency with guidelines. CONCLUSION: Systemic adjuvant therapy for node-negative breast cancer has gained acceptance. Better understanding of the decision-making process, of the perception of the risks and benefits involved, and of the impact of alternative strategies for the dissemination of consensus recommendations are needed to promote the use of chemotherapy in specific categories of women who are at high risk of recurrence.

Aged↗

Effect of multiple cilostazol doses on single dose lovastatin pharmacokinetics in healthy volunteers.

OBJECTIVE: To assess the effects of cilostazol on lovastatin pharmacokinetics. DESIGN: This was a single-centre, open-label, multiple dose, sequential treatment study. Participants received single oral doses of lovastatin 80 mg on days 1, 7 and 9, as well as oral cilostazol 100 mg twice daily on days 2 to 8, followed by a single oral 150 mg cilostazol dose on day 9. STUDY PARTICIPANTS: 15 healthy, nonsmoking male or female volunteers (aged 18 to 60 years) were enrolled, and 12 completed the study. MAIN OUTCOME MEASURES: Pharmacokinetic parameters were calculated using plasma concentrations of lovastatin and its beta-hydroxy metabolite and of cilostazol and its metabolites. Differences in the pharmacokinetics of each drug when given alone or in combination were assessed by analysis of variance. RESULTS: The maximum observed plasma concentration (Cmax) of lovastatin or its metabolite did not differ significantly when lovastatin was given alone and when it was given with 100 mg of cilostazol. The mean ratios of the area under the plasma concentration-time curve from zero to the time of the last measurable concentration (AUCt) for lovastatin coadministered with 100 mg of cilostazol to that with lovastatin given alone were 1.6 for lovastatin and 1.7 for its metabolite. With 150 mg of cilostazol, lovastatin Cmax did not change, whereas Cmax of the metabolite increased 2.2-fold. The mean AUCt ratios for lovastatin given with 150 mg cilostazol/lovastatin given alone were 1.6 and 2.0 for lovastatin and its metabolite, respectively. All increases in lovastatin and metabolite AUC were statistically significant, except for the 1.6-fold increase in lovastatin AUC with 150 mg of cilostazol. Maximum steady-state plasma drug concentration (Cssmax) and AUC during a dosage interval (AUC tau) for cilostazol 100 mg twice daily decreased 14 and 15%, respectively, upon lovastatin coadministration. CONCLUSIONS: Lovastatin and metabolite exposure is increased only by up to 2-fold when cilostazol is coadministered, which is considerably less than that observed for potent CYP3A inhibitors such as itraconazole and grapefruit juice. Absorption of cilostazol decreased approximately 15% when it was given with lovastatin. No dosage adjustments are necessary for cilostazol when coadministered with lovastatin, whereas lovastatin dose reductions may be needed when the 2 drugs are given together.

Adult↗

Type of mastectomy and quality of life for long term breast carcinoma survivors.

BACKGROUND: Despite numerous studies of partial mastectomy and psychologic morbidity in the first 24 months following surgery, little is known about the long term psychosocial repercussions of partial and total mastectomy. METHODS: The effect of the type of mastectomy on psychologic adjustment was assessed among 124 breast carcinoma survivors, 47 of whom underwent partial mastectomy and 77 of whom underwent total mastectomy, 8 years after initial treatment. Interviews were also conducted 3 and 18 months after surgery. Psychologic distress was assessed using the Psychiatric Symptom Index. Other outcomes included physical symptoms, patients' perceptions of their own health, satisfaction with the type of surgery performed and with the appearance of the scar, and marital and sexual adjustments. RESULTS: No statistically significant differences between partial and total mastectomy were observed with respect to long term quality of life. Age at diagnosis modified the relation between the type of mastectomy and psychologic distress in both the short term and the long term (P = 0.04). Among women younger than 50 years, partial mastectomy appeared to be protective against distress when compared with total mastectomy. In contrast, among women age 50 years or older, partial mastectomy was associated with higher psychologic distress levels at all interviews. CONCLUSIONS: Assessed globally, partial and total mastectomy appear to be equivalent treatments in terms of patients' long term quality of life. However, both short term and long term distress levels after partial and total mastectomy may depend on patients' age at diagnosis. The findings of this study suggest that the increased use of partial mastectomy may lessen the negative effects of breast carcinoma on younger survivors' quality of life. Nevertheless, total mastectomy may be an appropriate initial treatment for some women who truly choose it.

Adaptation, Psychological↗

Prognostic significance of stromelysin 3, gelatinase A, and urokinase expression in breast cancer.

This study was aimed at testing the hypothesis that the expression of proteases essentially produced by reactive stromal cells (stromelysin-3 [ST3], gelatinase A [GELA], and urokinase [uPA]) is predictive of prognosis in patients with breast cancer. This was a study of patients with node-positive and node-negative breast cancer diagnosed from 1980 to 1986 and with an average of 10 years follow-up. ST3 (665 cases), GELA, and uPA (575 cases each) expression was obtained by in situ hybridization on formalin-fixed, paraffin-embedded material using mRNA antisense probes. ST3 was expressed by 86.6% of the cases; GELA, 77.7%; and uPA, 64.7%. A significant correlation (P < .05) was found between high (more than 10%) ST3 expression and a younger age, lymph node involvement, poor nuclear grade, ductal histology, aneuploidy, and HSP-27 expression. High GELA expression was significantly associated with c-erbB2, ductal histology, and HSP-27 expression. High uPA expression correlated with poor nuclear grade, ductal histology, lack of estrogen and progesterone receptors, and p53 protein accumulation. High level of expression of all three proteases correlated significantly with each other and with cathepsin D expression by reactive stromal cells. By univariate analysis, both ST3 and uPA expression significantly predicted a shorter recurrence-free survival (ST3, P = .0199; uPA, P = .0269). By multivariate analyses, the prognostic significance was lost, most particularly at longer term. This study adds support to the concept that protease expression by reactive stromal cells is related to cancer cell characteristics but that their contribution to cancer progression is marginal.

Adult↗

Long-term quality of life after breast cancer: comparison of 8-year survivors with population controls.

PURPOSE: Quality of life of breast cancer survivors 8 years after diagnosis was compared with that among similarly aged women who had never confronted cancer (controls). METHODS: Survivors of a consecutive series of 227 breast cancer patients first treated in 1984 were approached for this study. Random-digit dialing was used to identify controls with the same age and residential distribution as the survivors. Quality of life was assessed in terms of physical health, functional status, psychologic distress, and social functioning. RESULTS: Participation was obtained from 96% (n = 124) of 129 eligible survivors and 61% (n = 262) of 427 potentially eligible controls. Consistently smaller proportions of survivors reported positive quality-of-life outcomes compared with controls, but these differences were generally small and nonsignificant statistically. When limited to women who remained free of disease over the entire follow-up period (n = 98), survivors' quality of life was similar to that among controls, with the exception of arm problems and sexual satisfaction for those women who lived with a partner. In contrast, survivors who developed recurrence or new primary breast cancer (n = 26) experienced a worse quality of life in all domains except social functioning. CONCLUSION: In most domains and for women without further disease events after diagnosis, quality of life does not seem to be permanently and globally impaired by breast cancer. Consequently, breast cancer survivors who remain free of disease probably do not need organized late psychosocial follow-up to improve quality of life. However, arm problems and sexuality are two areas in which additional effort may be still needed to improve quality of life of long-term survivors.

Activities of Daily Living↗

p53 and c-erbB-2 as markers of resistance to adjuvant chemotherapy in breast cancer.

Recent literature suggests that c-erbB-2 and p53 alteration might be linked to drug resistance. This study investigates the relation of c-erbB-2 oncoprotein overexpression and p53 protein accumulation with prognosis in patients with node-positive breast cancer (NPBC) and assesses the modifying effect of these markers on response to short (1-10 courses) or prolonged (> 10 courses) adjuvant chemotherapy. This study is based on 458 patients with NPBC diagnosed from 1980 to 1986, with an average of 10 years of follow-up. Marker expression was evaluated by immunohistochemical analysis on formalin-fixed, paraffin-embedded material with antibodies to c-erbB-2 and p53. c-erbB-2 was expressed in 17.2% of the cases, and 19.1% of the tumors stained positively for p53. By multivariate analysis, women with prolonged adjuvant chemotherapy had better survival than those with a short course of chemotherapy among patients whose tumor lacked c-erbB-2 oncoprotein expression (P = .0245) or p53 protein accumulation (P = .0477). Prolonged chemotherapy, however, was associated with little or no change in survival among patients whose tumor expressed those markers. The present study adds support to the hypothesis linking c-erbB-2 and p53 expression to drug resistance.

Adult↗

Determinants of persistent detection of human papillomavirus DNA in the uterine cervix.

To identify factors associated with persistence of human papillomavirus (HPV) DNA in the uterine cervix, 179 women who were 18-49 years old and who had normal cytologies and positive cervical HPV DNA test at a routine periodic examination were analyzed. Among them, 91 (50.8%) remained HPV-positive a few months (mean, 11 weeks) later. Persistence was higher in women who had used oral contraceptives for > or = 2 years (odds ratio, 3.9; 95% confidence interval, 1.5-10.3) compared with those who never used oral contraceptives or used them for <2 years. HPV types 16, 18, and 31/33/35 appeared more persistent (odds ratio, 2.5; 95% confidence interval, 1.0-6.2) than other types. Persistence seemed to increase with virus load and decrease with increasing interval between examinations.

Chronic Disease↗

Markers of chemoresistance in ovarian carcinomas: an immunohistochemical study of 86 cases.

Markers of chemoresistance have been rarely investigated in human ovarian cancer. This study evaluates the clinical value in ovarian cancer of metallothionein (MT), heat-shock protein-27 (HSP-27) and glutathione-S-transferase pi and alpha (GST pi, GST alpha), recognized for their relation with drug resistance in vitro. The expression of these markers was evaluated by immunohistochemistry on paraffin-embedded tumor specimens from 86 patients with ovarian carcinomas diagnosed between 1977 and 1990 who received chemotherapy. Response to chemotherapy was evaluated using well-defined criteria. Marker expression was evaluated on a section of the primary tumor (81 cases) and, when available, on a section of tumor following chemotherapy (48 cases). MT was expressed in 38.3% of primary tumors unexposed to chemotherapy, HSP-27 in 50.6%, GST pi in 37%, and GST alpha in 50.6%. The expression of all four markers did not help to predict chemoresistance. The concordance between marker expression by the tumor before and after chemotherapy was weak (concordance, 51.2%-70.7%). Immunostaining was not associated (p > 0.1) with any prognostic factor such as stage, residual tumor after surgery and grade. Ovarian cancer is a highly heterogeneous neoplasm and the expression of markers of chemoresistance reflects this heterogeneity. Our data suggest that chemoresistance is more likely multifactorial and confirms the complexity of the in vivo model.

Adult↗

Randomized trial of a psychologic distress screening program after breast cancer: effects on quality of life.

PURPOSE: Although psychosocial intervention can reduce psychosocial distress following breast cancer, many women who are experiencing problems are not identified and offered additional help. This trial assessed effects on quality of life of psychologic distress screening among newly diagnosed, nonmetastatic breast cancer patients. PATIENTS AND METHODS: From 1990 to 1992, all eligible patients in one regional breast cancer center were identified and offered study participation. Women in both control and experimental groups received brief psychosocial intervention from a social worker at initial treatment. The experimental group also had monthly telephone screening of distress levels using a brief, validated instrument, with additional psychosocial intervention offered only to those with high distress at screening. RESULTS: Among 282 eligible patients, 89% were randomized and completed the study. Participants' psychologic distress levels decreased over the study period (P = .0001). However, no between-group differences were observed. Mean distress scores among control and experimental women at 0-, 3-, and 12-month interviews were 20.7 and 20.4, 15.5 and 15.0, and 14.6 and 13.5, respectively. No between-group differences were observed with respect to physical health, functional status, social and leisure activities, return to work, or marital satisfaction. CONCLUSION: Our results indicate that, among patients who receive a minimal psychosocial intervention as part of their initial cancer care, a distress screening program does not improve quality of life. Minimal psychosocial intervention at initial treatment may be effective in reducing distress, thus making it difficult to obtain additional benefit from a screening program.

Breast Neoplasms↗

Social support and survival among women with breast cancer.

BACKGROUND: Two recently reported randomized trials, one among patients with advanced breast cancer and the other among patients with early stage melanoma, suggested that social support may affect survival favorably. This study assesses relationships of social support indicators with 7-year survival among women diagnosed with localized or regional stage breast cancer. METHODS: All newly diagnosed patients with surgically treated localized or regional disease in seven Quebec City hospitals in 1984 were considered for this analysis. Among 235 eligible patients, 224 (95%) participated in a home interview 3 months after surgery. This interview provided information on the use of confidants in the 3 months after surgery. Data on disease and treatment characteristics were abstracted from patients' medical records. RESULTS: Compared with women who used no confidant in the 3 months after surgery, the hazard ratio for the 7-year period was 0.61 (95% confidence interval [CI], 0.33-1.12) among those who had used at least one confidant, 0.54 (95% CI, 0.28-1.06) in women who used two or more types of confidant, and 0.51 (95% CI, 0.22-1.18) among those whose confidants included either physician or nurse. These results were adjusted for age, presence of invaded axillary lymph nodes, adjuvant radiotherapy, and adjuvant systemic therapy (hormone or chemotherapy). CONCLUSION: These results support the view that social support may be associated with longer survival among women with localized or regional stage breast cancer.

Breast Neoplasms↗

Prognostic significance of heat-shock protein-27 in node-positive breast carcinoma: an immunohistochemical study.

Immunostaining for heat-shock protein-27 (HSP-27) was performed on formalin fixed-paraffin embedded sections of 890 node-positive breast carcinomas resected between 1980 and 1986. The follow-up ranged from 2.5 to 10.5 years. A polyclonal antibody (Hu27, dilution: 1/200) was used. A positive cytoplasmic staining was obtained in 383 cases (43%). No difference in distant metastasis-free survival (DMFS) or overall survival (OS) was noted between cases with positive or negative immunostaining. This study suggests that HSP-27 expression is not predictive of the outcome in node-positive breast cancer.

Breast Neoplasms↗

Maternal work during pregnancy and the risks of delivering a small-for-gestational-age or preterm infant.

OBJECTIVE: The objective of this study was to assess the relation of some maternal job characteristics to the risks of delivering a small-for-gestational-age or preterm infant. METHODS: Altogether 4390 women who lived in Quebec City, Canada, and the surrounding area, and who gave birth between January and October 1989 to a singleton liveborn neonate were included. Information on gestational age at delivery, job characteristics, nonoccupational physical activities, and several potential confounders was obtained in a telephone interview a few weeks after the delivery. Birthweight was recorded from the birth certificate. RESULTS: The risk of having a small-for-gestational-age infant (birthweight lower than the 10th percentile for gestational age and gender) was increased among the women who worked at least 6 h a day in a standing position. The adjusted odds ratios (OR) were 1.00, 1.13 [95% confidence interval (95% CI) 0.83-1.55], and 1.42 (95% CI 1.02-1.95) for the women working in a standing position < 3, 3-5, and > or = 6 h a day, respectively. The risk for a small-for-gestational-age infant also slightly increased as the gestational age at work cessation increased. A modest increment in the risk of delivering preterm (OR, 1.45, 95% CI 0.84-2.49) was observed for the women working regularly in the evening or at night. Physical effort, lifting heavy objects, and long workhours were not related to either a small-for-gestational-age or a preterm infant. CONCLUSIONS: The results indicate that prolonged standing and working late into pregnancy may increase the risk of delivering a small-for-gestational-age infant, whereas regular evening or night work may be a risk factor for preterm birth.

Adult↗

Risk factors for cervical intraepithelial neoplasia: differences between low- and high-grade lesions.

This case-control study assesses relations of human papillomavirus (HPV) type 16 infection, sexual history, cigarette smoking, and oral contraceptive use to low- and high-grade cervical intraepithelial neoplasia (CIN). A total of 548 high-grade and 338 low-grade CIN cases and 612 controls were identified among women seen at a colposcopy clinic in Quebec, Quebec, Canada, in 1988-1989. Interviews, colposcopy, cervical scrapings, and colposcopically directed biopsies were performed. One pathologist reviewed all histologic slides. Southern blot techniques were used to assay specimens for HPV 16 DNA. Lifetime number of sexual partners was related to low- and high-grade CIN. Presence of HPV 16 DNA was associated with a 8.7-fold (95% confidence interval 5.1-15.0) elevation in estimated relative risk of high-grade CIN. Relative risk of high-grade CIN increased with amount of HPV 16 DNA (p < 0.0001). Estimated relative risk of high-grade CIN in current cigarette smokers was 2.4 (95% confidence interval 1.8-3.2) compared with never smokers and increased with number of pack-years of exposure (p < 0.0001). Long-term (6 years or more) users of oral contraceptives had an estimated relative risk of high-grade CIN of 1.9 (95% confidence interval 1.1-3.3) compared with those who never used such contraceptives. In contrast, presence of HPV 16 DNA, cigarette smoking, and oral contraceptive use showed little or no relation to low-grade CIN. Risk factors for low- and high-grade CIN may differ substantially.

Adult↗

Prognostic significance of HER-2/neu oncoprotein expression in node-positive breast cancer. The influence of the pattern of immunostaining and adjuvant therapy.

BACKGROUND: The influence of HER-2/neu on prognosis of breast cancer is controversial. The authors investigated by immunohistochemistry in node-positive disease the influence of the pattern of immunostaining (membranous or cytoplasmic) on outcome and the prognostic significance of this marker in patients receiving or not receiving adjuvant therapy. METHODS: The immunostaining for HER-2/neu oncoprotein was performed on formaldehyde-solution-fixed, paraffin-embedded sections of 888 node-positive breast cancers resected between 1980 and 1986 and for which a follow-up of 2.5-10.5 years was available. The staining was performed using a polyclonal antibody (dilution, 1/15). RESULTS: One hundred forty-three cases (16.1%) revealed a positive membrane staining with or without additional cytoplasmic contribution, whereas cytoplasmic staining alone was noted in 118 cases (13.3%). Positive membrane staining was correlated with more involved lymph nodes (P = 0.005), aneuploidy (P = 0.002), poor nuclear (P < 0.0001) and histologic (P = 0.007) grades, absence of estrogen (P < 0.0001) and progesterone (P < 0.0001) receptor content, and cathepsin D expression (P = 0.009). No relation was found (P > 0.05) with either age, tumor size, or HSP27 expression. Membrane staining was strongly associated with poor distant metastasis-free or overall survival rate (P < 0.0001), whereas cytoplasmic staining had no prognostic significance. Two hundred thirty-two patients (26.1%) received no additional treatment after surgery. The difference in survival rates between cases with positive and negative staining was only significant among patients submitted to adjuvant chemotherapy or hormone therapy. CONCLUSIONS: This study strongly supports the association of HER-2/neu oncoprotein expression with poor prognosis in node-positive breast cancer and demonstrates that membranous but not cytoplasmic staining is prognostically relevant. It also shows that HER-2/neu oncoprotein expression is useful in predicting survival time only in patients receiving adjuvant therapy, thus suggesting that it may be a marker of drug resistance.

Adult↗