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M Robson

Publications and source records attributed to M Robson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations.

BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes are associated with an increased risk of breast cancer. Whether women with breast cancer who have inherited mutations in these genes have a different outcome after breast conservation therapy than women with "sporadic" cancer is unresolved. Consequently, we compared the outcomes after breast conservation therapy in Ashkenazi women with or without germline mutations in BRCA1 and/or BRCA2 (hereafter called BRCA). METHODS: We studied 305 women of Ashkenazi Jewish descent undergoing breast-conserving treatment for 329 invasive breast cancers. We reviewed their clinical records, retrieved their archival tissue samples, and tested those samples for the founder mutations BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT. Genetic results were linked to clinical data and outcomes by univariate and multivariate analyses. All Pvalues are two-sided. RESULTS: We detected mutations in BRCA genes in 28 of 305 women. Women with BRCA mutations were more likely to be diagnosed with cancer before the age of 50 years (P<.001) and to have lymph node involvement (P =.04). Ipsilateral breast tumor recurrence was more common in women with BRCA mutations, although this did not reach statistical significance (relative risk [RR] = 1.79; 95% confidence interval [CI] = 0.64-5.03). Women with mutations were more likely to develop contralateral breast cancer (RR = 3.50; 95% CI = 1.78-8.74; P =.001). Distant disease-free survival was shorter in women with mutations (66.2% versus 84.3% at 10 years; P =.05), as was breast cancer-specific survival (71.9% versus 87.2% at 10 years; P =.02). Tumor stage and nodal status, but not mutation status, were predictive of distant disease-free and breast cancer-specific survival in multivariate analysis. CONCLUSIONS: Women with BRCA founder mutations are at increased risk for breast cancer-related events after breast conservation. However, mutation status is not an independent predictor of survival and should not influence decisions regarding adjuvant therapy. The increased contralateral breast cancer risk in women heterozygous for BRCA mutations mandates careful surveillance.

Analysis of Variance↗
PubMed1999

Localized male breast carcinoma and family history. An analysis of 142 patients.

BACKGROUND: Male breast carcinoma is rare; therefore, the effect of family history on the course of the disease has not been well described. Germ-line mutations in breast carcinoma susceptibility genes, particularly BRCA2, are associated with an increased risk of male breast carcinoma. The authors sought to correlate significant family history with clinical phenotype in males with breast carcinoma. METHODS: One hundred forty-two men with breast carcinoma were treated at Memorial Sloan-Kettering Cancer Center or the Ochsner Clinic from 1973 to 1994. The authors reviewed the effect imparted by a family history of breast carcinoma on the duration of symptoms, the age at diagnosis, and the survival of men with this disease. RESULTS: Fifteen percent of male breast carcinoma patients had a first-degree relative with the disease. Fifty-eight years was the mean age at diagnosis for those with a family history, compared with 61 years for those without (P = not significant [NS]). The mean duration of symptoms was 23 months for those with a family history, compared with 22 months for those without. Three of 22 patients (13.6%) with a family history, compared with 11 of 90 patients (12%) without a family history, had Stage III disease (P = NS) at presentation. The overall 5-year and 10-year survival rates were 86% and 64%. Survival was not affected by family history. Lymph node positivity reduced 5-year and 10-year survival rates to 73% and 50% (P = 0.0004). CONCLUSIONS: For men with breast carcinoma, the presence of a family history did not affect the age at presentation, the duration of symptoms, the stage of disease at presentation, or the overall survival. In multivariate analysis, the most powerful predictor of outcome for these men was the status of the axillary lymph nodes.

Adult↗
PubMed1998

BRCA-associated breast cancer: absence of a characteristic immunophenotype.

To characterize the biological features of breast cancer associated with germ-line mutations in BRCA1 and BRCA2, invasive tumors were studied from 58 Jewish women ascertained through studies of early-onset breast cancer. All women were tested for the BRCA1 founder mutations 187delAG (commonly known as 185delAG) and 5385insC (commonly known as 5382insC) and the BRCA2 founder mutation 6174delT. Mutations were detected in 17 of 58 (29.3%) women. Comparing BRCA-associated breast cancers (BABCs) to cases arising in women without founder mutations, no differences were noted in tumor size, tumor stage, or frequency of axillary nodal involvement. Infiltrating ductal carcinoma was the predominant histological type in both groups. BABCs were significantly more likely to be of histological grade III (100 versus 63%; P = 0.04), estrogen receptor negative (75 versus 35%; P = 0.004), and HER2/neu negative (87 versus 58%; P = 0.04). An associated intraductal component was present in 59% of BABCs and 76% of cancers not associated with mutations (P = not significant). A high Ki-67 labeling index was more commonly observed in BABCs than in cases without mutations (83 versus 48%; P = 0.09). There were no differences between the two groups in the frequency of expression of epidermal growth factor receptor, cathepsin D, bcl-2, p27, p53, or cyclin D. There were no significant differences in relapse-free or overall survival. These observations suggest that breast cancers arising in Jewish women with germ-line BRCA founder mutations have a greater proliferative potential than cancers in women without such mutations. Additional studies of BABC are required to determine the nature and implications of additional genetic abnormalities occurring in these tumors.

Adult↗
PubMed1998

Nondisruptive, in vivo method for biomechanical characterization of linear incision wound healing: preliminary report.

Previous work on in vivo biomechanical characterization of soft tissues and wound healing has led to the development of a methodology for nondisruptive, in vivo biomechanical analysis of linear incision wounds. The purpose of this preliminary study was to define nondisruptive biomechanical parameters that characterize progressive healing and compare them with an in vivo disruptive parameter of ultimate pressure at failure (in vivo strength). Male Sprague-Dawley rats (n = 60), each weighing 250 to 300 gm, were anesthetized and underwent creation of paired full-thickness linear incision wounds. The rats were divided into three groups (n = 10/group per time period): control group, nothing applied to either wound; carrier group, bovine serum albumin applied to each wound; transforming growth factor-beta2 group, transforming growth factor-beta2 in bovine serum albumin applied to each wound. On postoperative days 5 and 10, rats from each group underwent in vivo biomechanical testing using the Dimensional Analysis System (Dimensional Analysis Systems, Inc., Nashville, Tenn.). This computer-driven device integrates a video camera and processor with a vacuum controller, valve, and transducer to provide measurements of tissue deformation (in millimeters) and negative pressure (mmHg) as a multiaxial stress (vacuum) is applied to a wound. On each rat, one incision was tested disruptively and the other incision was tested nondisruptively. Disruptive data were measured as ultimate pressure (mmHg) at failure, or the amount of pressure required to disrupt the wound. Nondisruptive data were measured for tissue stiffness (kiloPascals) during application of negative pressure (maximum, 80 mmHg). On postoperative day 5, wounds treated with transforming growth factor-beta2 had significantly increased in vivo wound strength compared with carrier wounds. The nondisruptive parameter of tissue stiffness was also significantly increased for the transforming growth factor-beta2 treated wounds, thus supporting the disruptive data. On postoperative day 10, there was no difference in mean wound strength or mean tissue stiffness among any of the groups. These preliminary data represent the first report of in vivo, nondisruptive biomechanical characterization of linear incision wounds. The results suggest that through in vivo measurements of tissue stiffness, differences can be detected between treatment groups. Because the healing wound may be characterized without the need for disruption, this methodology should allow for consecutive, in vivo biomechanical testing of wounds in future wound healing studies.

Animals↗
PubMed1998

BRCA-associated breast cancer in young women.

PURPOSE: To delineate the clinical characteristics and outcomes of breast cancer that arises in the setting of a germline BRCA mutation and to compare BRCA-associated breast cancers (BABC) with those that arise in women without mutations. PATIENTS AND METHODS: We reviewed the clinical records of 91 Ashkenazi Jewish women ascertained during studies of the genetics of early-onset breast cancer. All women underwent testing for the BRCA1 mutations 185delAG and 5382insC. After the discovery of BRCA2, 79 women were also tested for the BRCA2 mutation 6174delT. RESULTS: Mutations were identified in 30 women (33%). BABC were less likely to present with stage I disease than cases in women without mutations (27% v 46%), more likely to have axillary nodal involvement (54% v46%), and more likely to have extensive axillary involvement (25% v 17%). These differences were not statistically significant. BABC were significantly more likely to be histologic grade III (100% v 59%, P=.04) and to be estrogen receptor-negative (70% v 34%, P=.04). In the entire cohort, there were no significant differences between BABC and non-BRCA-associated cancers in 5-year relapse-free survival (65% v 69%, P=not significant [NS]), 5-year event-free survival (57% v 68%, P=NS), or 5-year overall survival. However, among cases diagnosed within 2 years of study entry, there was a trend toward shorter event-free survival in BRCA heterozygotes, but not relapse-free survival. Women with germline BRCA mutations were significantly more likely to develop contralateral breast cancer at 5 years (31% v 4%, P=.0007). CONCLUSION: BABC present with adverse clinical and histopathologic features when compared with cases not associated with BRCA mutations. However, the prognosis of BABC appears to be similar to that of nonassociated cancer. Further studies of incident cases are necessary to define the independent prognostic significance of germline BRCA mutations.

Adult↗
PubMed1998

Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk.

PURPOSE: Previous studies of mutations in BRCA1 or BRCA2 have used detection methods that may underestimate the actual frequency of mutations and have analyzed women using heterogeneous criteria for risk of hereditary cancer. PATIENTS AND METHODS: A total of 238 women with breast cancer before age 50 or ovarian cancer at any age and at least one first- or second-degree relative with either diagnosis underwent sequence analysis of BRCA1 followed by analysis of BRCA2 (except for 27 women who declined analysis of BRCA2 after a deleterious mutation was discovered in BRCA1). Results were correlated with personal and family history of malignancy. RESULTS: Deleterious mutations were identified in 94 (39%) women, including 59 of 117 (50%) from families with ovarian cancer and 35 of 121 (29%) from families without ovarian cancer. Mutations were identified in 14 of 70 (20%) women with just one other relative who developed breast cancer before age 50. In women with breast cancer, mutations in BRCA1 and BRCA2 were associated with a 10-fold increased risk of subsequent ovarian carcinoma (P = .005). CONCLUSION: Because mutations in BRCA1 and BRCA2 in women with breast cancer are associated with an increased risk of ovarian cancer, analysis of these genes should be considered for women diagnosed with breast cancer who have a high probability of carrying a mutation according to the statistical model developed with these data.

Adult↗
PubMed1998

Accumulation of chlorpyrifos on residential surfaces and toys accessible to children.

Quantitative examination of major pathways and routes of exposure to pesticides is essential for determining human risk. The current study was conducted in two apartments and examines the accumulation of the pesticide chlorpyrifos in childrens' toys after the time suggested for reentry after application. It has been established for the first time that a semivolatile pesticide will accumulate on and in toys and other sorbant surfaces in a home via a two-phase physical process that continues for at least 2 weeks postapplication. A summation of the above for a 3-6-year-old child yielded an estimated nondietary total dose of 208 microg/kg/day. Potential exposure from the inhalation pathway was negligible, while dermal and nondietary oral doses from playing with toys contributed to 39 and 61% of the total dose, respectively. If children with high frequency mouthing behavior are considered as candidates for acute exposure to chlorpyrifos residues, the estimated acute dose could be as high as 356 microg/kg/day. Routine reapplication of pesticides could lead to continued accumulation in toys and other sorbant surfaces, e.g., pillows, with large sorbant reservoirs, which can become a long-term source of exposure to a child. Estimates of a child's nondietary exposure to chlorpyrifos associated with toys and other sorbant surfaces for a period of 1 week following application appear to be of public health concern, and studies of actual childhood exposure from this pathway are warranted in the home environment. The above information should be used to determine if current procedures for postapplication reentry are sufficient and to evaluate the need for procedures to store frequently used household toys, pillows, and other sorbant objects during insecticidal application.

Air Pollution, Indoor↗
PubMed1997

Prevalence of recurring BRCA mutations among Ashkenazi Jewish women with breast cancer.

The BRCA1 mutations 185delAG and 5382insC and the BRCA2 mutation 6174delT have been detected in a significant proportion of Ashkenazi Jewish women with early-onset breast cancer. A group of 236 Jewish women with breast cancer was screened for the presence of these alterations. Mutations were detected in 25.0% (59/236). Among women with breast cancer diagnosed at or before the age of 45, the prevalence of these mutations was 29.1% (42/144). Among women diagnosed with breast cancer after age 45, mutations were noted in 18.5% (17/92). Among women with a family history of breast or ovarian cancer, the likelihood of detecting a mutation was 32.1% (53/165). BRCA1 185delAG was the most common mutation overall (40/236, 16.9%). The ratio of BRCA1 185delAG to BRCA2 6174delT was 4.0 in women with early-onset breast cancer and 1.3 in women with breast cancer diagnosed after age 45. Clinical features such as age at diagnosis, family history of breast or ovarian cancer, bilateral breast cancer, and personal history of breast and ovarian cancer increase the likelihood of detecting mutations among Ashkenazi women with breast cancer. The yield of testing is low in the absence of any of these features.

Adult↗
PubMed1996

How is androgen-dependent metastatic prostate cancer best treated?

The principles of management of newly diagnosed metastatic prostate cancer have changed little since the time of Huggins and his colleagues. Modern clinicians have many more weapons in their therapeutic armamentarium than those pioneers, but little progress has been made in improving the survival of men with this disease. The results of androgen deprivation are comparable using any one of a number of different monotherapy approaches. The use of combined androgen blockade may improve survival in men with minimal disease but at considerable economic cost and with significant impairment of quality of life. The benefit of this therapy for men with more extensive disease is uncertain. New modalities such as intermittent androgen blockade or combination therapies are exciting, but unproven.

Adenocarcinoma↗
PubMed1996

Haemolytic disease of the newborn due to anti-G.

Mrs P. presented at 13 weeks of gestation with apparent anti-C+D. At week 34, with antibody levels of 168 IU/ml, a D-negative (r'r) baby was delivered with a strongly positive DAT and an Hb of 3.0 g/dl. Anti-G in maternal serum was isolated by adsorption and elution from R2R2 cells and shown, using flow-cytometric and chemiluminescence assays, to sensitize r'r cells at levels of cell-bound IgG consistent with fetal haemolysis. In an analysis of 28 sera from alloimmunized women with over 5 IU/ml anti-C+D, 2 sera were shown to contain levels of anti-G consistent with moderate or severe haemolytic disease of the newborn (HDN). Thus HDN due to anti-G may not be rare. An analysis of 187,037 blood donors in the south-west of England showed the r' gene frequency to be 0.005897 suggesting that approximately 2.9% of matings of rr women with D-negative fathers can produce an r'r baby. These findings highlight the need for the continuous non-invasive monitoring of D-negative fetuses of women with apparent anti-C+D.

Antibodies, Anti-Idiotypic↗
PubMed1994

Effects of granulocyte-macrophage colony-stimulating factor on wound contraction.

The effect of topical recombinant murine and human GM-CSF, 1 or 10 micrograms/cm2 for one to ten days, on the contraction and healing of acute and chronic granulating wounds infected with Escherichia coli was studied in Sprague-Dawley rats. Bacterial contamination of wounds produced significant inhibition of wound contraction. Application of GM-CSF at either dose level to infected wounds markedly increased the rate of wound closure compared to the rate in infected untreated controls. Ten days treatment was found to be more effective than a single application. An advanced stage of wound healing was observed at ten days in the GM-CSF-treated rats compared with controls. Bacterial counts decreased in the GM-CSF-treated wounds which may suggest bactericidal activity. Topical treatment with GM-CSF was shown to effectively inhibit the retardation of wound closure produced by bacterial contamination and may therefore be useful in the management of patients with infected wounds.

Administration, Topical↗
PubMed1994

Doppler ultrasound of the uteroplacental circulation in the prediction of pregnancy outcome in women with raised maternal serum alpha-fetoprotein.

OBJECTIVE: To determine whether Doppler waveforms from the uteroplacental circulation could improve the prediction of pregnancy outcome in women with raised maternal serum alpha-fetoprotein and a structurally normal fetus. The study further attempts to determine whether the presence of an early diastolic notch would constitute a better screening test than waveform patterns. DESIGN: An observational study. SETTING: A tertiary referral obstetric service. SUBJECTS: All women referred to St George's Hospital with a raised maternal serum alpha-fetoprotein had waveform measurements from the uteroplacental circulation after exclusion of fetal abnormalities. Pregnancy outcome was determined by questionnaire sent to the referring clinicians. MAIN OUTCOME MEASURES: Adverse perinatal outcome in the form of preterm labour, low birthweight and perinatal mortality. RESULTS: Data from 332 cases were available for analysis. Women with a normal pattern of uteroplacental waveforms had a perinatal mortality of 9.6/1000. Women with a uniform high resistance pattern had a perinatal mortality of 846/1000, and those with a mixed resistance pattern had a perinatal mortality of 268/1000. Overall there were 27 cases of placental abruption which accounted for eight of the 50 perinatal deaths. The remainder were due to prematurity or low birthweight or both. The presence of the early diastolic notch did not improve on the waveform patterns in the prediction of perinatal death. CONCLUSION: Women with raised maternal serum alpha-fetoprotein and normal Doppler waveform patterns from the uteroplacental circulation can be reassured, but mixed or uniform high resistance patterns should encourage increased surveillance and a search for intervention therapies.

Blood Flow Velocity↗
PubMed1994

Low dose aspirin in women with raised maternal serum alpha-fetoprotein and abnormal Doppler waveform patterns from the uteroplacental circulation.

OBJECTIVE: To investigate the use of low dose aspirin in the reduction of perinatal morbidity and mortality in women with unexplained raised maternal serum alpha-fetoprotein and abnormal uteroplacental Doppler waveform patterns. DESIGN: Prospective randomised controlled trial. SETTING: A tertiary referral obstetric service. SUBJECTS: One hundred and sixty-four women referred to our unit with raised maternal serum alpha-fetoprotein and a structurally normal fetus had abnormal uteroplacental Doppler waveform patterns at 24 weeks of gestation. INTERVENTION: Women were randomly allocated to two groups, receiving either low dose aspirin 75 mg (n = 76) or placebo (n = 88) daily until delivery. MAIN OUTCOME MEASURES: Preterm labour, low birthweight, the occurrence of placental abruptions and perinatal mortality. RESULTS: The frequency of severely small for gestational age infants (birthweight < 5th centile) was reduced in the aspirin treated group to 16% compared with 25% in the placebo group (95% CI-21% to 13%). The frequency of delivery before 34 weeks of gestation was 26% in the aspirin group and 42% in the placebo group (95% CI--30% to 1%). The perinatal mortality was 240/1000 in the aspirin group and 320/1000 in the placebo group (95% CI--22% to 6%). None of these reductions was statistically significant. Although the frequency of placental abruptions was similar in the two groups, significantly more babies died from abruption in the aspirin treated group (91% versus 30%, 95% CI 28% to 94%). Low dose aspirin did cause a significant reduction (P = 0.008) in deaths from causes other than placental abruption. CONCLUSION: This trial revealed a benefit of low dose aspirin therapy in women with raised maternal serum alpha-fetoprotein and abnormal uteroplacental Doppler waveform patterns, but the effect was smaller than expected. Although a reduction in deaths from small preterm babies was observed, there was an increase in the number of deaths following placental abruption without a significant increase in the number of abruptions. We recommend that this should be considered before giving aspirin to these high risk women and that other investigators should specifically look for this effect.

Adult↗