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Biomedical subjects

N Bundred

Publications and source records attributed to N Bundred.

15 recordsLinked to original sources
PubMed2006

Screening younger women with a family history of breast cancer--does early detection improve outcome?

Women with a family history are often offered mammographic surveillance at an earlier age and with greater frequency than those in the National Breast Screening Programme. In this study, we compared the survival of 62 breast cancer patients diagnosed in the context of a family history clinic offering 12-18 monthly mammographic screening with that of 1108 patients of the same age range but having no exposure to screening. We subtracted the expected additional observation time due to lead time from the survival of the screen-detected cases. Survival was significantly better in the family history group with relative hazards of 0.19 (95% CI 0.07-0.52, P<0.001) for breast cancer death and 0.19 (95% CI 0.08-0.43, P<0.001) for disease-free survival. After correcting for lead-time, the relative hazards were 0.24 (95% CI 0.09-0.66, P=0.005) for breast cancer death and 0.25 (95% CI 0.11-0.57, P<0.001) for disease-free survival. These results strongly suggest that screening younger women with a family history of breast cancer leads to improved survival. More precise estimates of the benefit will accrue from further follow-up and other such studies.

Adult↗
PubMed2005

The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: To assess the effects of tibolone on climacteric symptoms, endometrium and serum lipid/lipoproteins in postmenopausal women receiving tamoxifen after surgery for breast cancer. DESIGN: Double-blind, randomised, placebo-controlled, multicentre pilot study. SETTING: Hospital outpatient clinic. SAMPLE: Seventy postmenopausal women receiving tamoxifen following surgery for early breast cancer. METHODS: Women received 20 mg/day oral tamoxifen plus either 2.5 mg/day oral tibolone or placebo for 12 months. MAIN OUTCOME MEASURES: Frequency and severity of hot flushes (diary cards); intensity of hot flushes and sweats (Landgren scale); interference of hot flushes and sweats with normal life; frequency and intensity of other climacteric symptoms; endometrial thickness and histology; vaginal bleeding; breast cancer recurrence and serum lipid/lipoproteins. RESULTS: Daily card data showed no change in the daily number of hot flushes with either tibolone or placebo (P= 0.219) after three months. There was a significant reduction in the severity of flushes with tibolone compared with placebo (-0.4 vs 0.2, P= 0.031). The Landgren scale showed a mean change in the number of hot flushes of -0.6 with tibolone and +1.1 with placebo after 12 months (P= 0.022). Endometrial biopsies were normal and vaginal bleeding was similar in both groups. A significant decrease in triglycerides (-23% vs 1.4%) and HDL (-12% vs 19%) was seen with tibolone compared with placebo after 12 months. CONCLUSIONS: Tibolone prevented an increase in hot flushes in postmenopausal women given tamoxifen following surgery for breast cancer without untoward effects on the endometrium. Beneficial effects on serum lipid profile were noted.

Administration, Oral↗
PubMed2003

Management of accessory breast tissue in the axilla.

BACKGROUND: Accessory breasts occur in 0.4-6 per cent of women. They may be asymptomatic or cause pain, restriction of arm movement, cosmetic problems or anxiety. It is currently recommended that all accessory breasts be removed surgically but complications following this procedure have been poorly documented. METHODS: All patients who presented with axillary accessory breasts between July 1999 and October 2000 were identified from a computer database. A retrospective review of patients listed for excision of accessory breast tissue was undertaken to determine any postoperative complications. RESULTS: Women with axillary accessory breasts represented 0.5 per cent of all new referrals. A total of 28 women (80 per cent of those diagnosed) had surgery. Eleven patients experienced postoperative complications; the majority followed operations performed by a trainee. CONCLUSION: Excision of accessory axillary breast tissue was associated with significant morbidity.

Axilla↗
PubMed2002

Will early detection of non-axillary sentinel nodes affect treatment decisions?

Axillary lymph node involvement is the best prognostic factor for breast cancer survival. Staging breast cancers by axillary dissection remains standard management and is part of the UK national guidelines for breast cancer treatment. In the presence of involved axillary lymph nodes best treatment has been shown to be axillary clearance (Fentiman and Mansell, 1991), but clearly for women whose nodes are uninvolved avoidance of morbidity is optimal and this will be achieved by minimal dissection of the axilla. Thus, for node-negative women the introduction of the sentinel node biopsy technique may revolutionise the approach to the axilla. These will be women with mammographic screen detected small well and moderately differentiated tumours (Hadjiloucas and Bundred, 2000). The impact of sentinel node biopsy in women who have symptomatic large tumours is unproven, and around half of these women will require a second procedure to clear their axilla or radiotherapy as treatment. Even for those women found to have involved sentinel lymph nodes the ability to use early systemic chemotherapy followed by axillary clearance or radiotherapy may provide long-term survival gains. Sentinel node biopsy should not, however, become routine practice until randomised controlled trials have proven its benefit and safety in reducing morbidity. Several randomised controlled trials (including ALMANAC) are currently underway.

Breast Neoplasms↗
PubMed2000

Plasma levels of soluble CD105 correlate with metastasis in patients with breast cancer.

CD105 (endoglin), a receptor for transforming growth factor (TGF) beta1 and beta3 in vascular endothelial cells, is highly up-regulated in blood vessels of tissues where neovascularisation occurs. It modulates endothelial-mesenchymal signalling and is essential for angiogenesis. Indeed, CD105 knock-out mice die from malvascularisation by 11.5 day p.c. In the present study CD105, TGFbeta1 and CD105/TGFbeta1 complexes were quantified in plasma samples from 77 healthy individuals and 92 patients with early stage breast cancer prior to any treatment. When compared with normal controls, both CD105 and CD105/TGFbeta1 complex levels were significantly elevated in breast cancer patients, whereas TGFbeta1 levels were lower in cancer patients. The most important finding to emerge was that CD105 levels were significantly increased in patients who developed distant metastasis compared with disease-free patients. While there was no significant difference between CD105 levels in controls compared to disease-free patients, it was significantly higher in patients with metastatic disease. Thus patients who had died following local relapse or distant metastases possessed the highest levels of CD105. Neither CD105/TGFbeta1 complex nor TGFbeta1 levels correlated with tumour progression. Our data indicate that CD105 might be a valuable novel angiogenic marker for identifying breast cancer patients who are at high risk of developing metastasis.

Adult↗
PubMed2000

Radioimmunoassay for the measurement of thrombospondin in plasma and breast cyst fluid: validation and clinical application.

Thrombospondin is an adhesive protein that has been implicated in malignancy, specifically in tumour progression and angiogenesis. We developed a radioimmunoassay for the measurement of thrombospondin in plasma and breast cyst fluid. The assay exhibited high accuracy, with recoveries of 102-136% and acceptable imprecision, with an intra-assay coefficient of variation (CV) of <7.5% across the analytical range 30-1000 ng/mL and inter-assay CV of 4.4% and 7.7% at 152 and 224 ng/mL, respectively. Thrombospondin measured in the breast cyst fluid of patients with gross cystic disease of the breast showed that patients with type II (Na+) cysts had significantly higher concentrations than type I (K+) cysts. The plasma thrombospondin reference range was determined as 131-274 ng/mL. Patients with breast cancer had significantly higher plasma thrombospondin concentrations than normal individuals or patients with benign breast disease. Plasma thrombospondin was higher in breast cancer patients with lymph node involvement.

Adult↗
PubMed1999

Breast carcinoma: vascular density determined using CD105 antibody correlates with tumor prognosis.

Angiogenesis is essential for tumor growth and metastasis. There are conflicting reports as to whether microvessel density (IMD) in breast cancers is associated with prognosis. This could be due to the use of different antibodies to endothelial cell markers, variation in tissue pretreatment protocols, and nonstandardized counting methods. We have assessed the IMD in 106 breast carcinomas using a pan-endothelial marker, CD34, and a recently described mAb to CD105, which preferentially reacts with endothelial cell in angiogenic tissues. IMD values (separated as above or below median) for CD105 expression showed a statistically significant correlation with overall (P = 0.0029) and disease-free survival (P = 0.0362). In contrast, blood vessel counts using a panendothelial marker CD34 did not correlate with overall or disease-free survival (P = 0.2912 and P = 03153, respectively). When IMD values were subdivided into quartiles and assessed for their prognostic values, there was a statistically significant difference in the overall survival across CD105, but not CD34, values (P = 0.0017 and P = 0.7997, respectively) and also disease-free survival (P = 0.0431 and P = 0.5066, respectively). Further analysis of IMD values demonstrated that there were no deaths in the lowest quartile for CD105 and it differed from the other three quartiles. However, examination of clinical details of patients in the lowest quartile failed to reveal clustering of patients known to be associated with low-risk factors. Multivariate analysis confirmed that IMD values using CD105 were an independent prognostic factor. These results suggest that the ability to quantitatively distinguish between tumor neovascularization and preexisting vessels may be important in the assessment of tumor angiogenesis, but requires confirmation in a greater number of patients with a longer follow-up.

Adult↗
PubMed1999

Serum parathyroid hormone-related protein levels and response to bisphosphonate treatment in hypercalcemia of malignancy.

The pathogenesis of hypercalcemia of malignancy comprises increased net bone resorption and enhanced renal tubular reabsorption of calcium (Ca). To evaluate the prevalence of an increased renal tubular reabsorption of Ca index [tubular reabsorption of calcium index (TRCaI)] in cancer patients with hypercalcemia and of elevated circulating levels of PTH-related protein (PTHrP), which is recognized as a major mediator of this syndrome, we investigated 315 well rehydrated patients, aged 58.1 +/- 0.7 yr (mean +/- SEM), with hypercalcemia [albumin-corrected plasma Ca (pCa), >2.7 mmol/L] secondary to histologically proven malignancy. Changes in pCa and, therefore, various Ca filtered loads were obtained by different degrees of bone resorption inhibition achieved with a single infusion of the bisphosphonate ibandronate, given at various doses on a randomized, double blind basis. PTHrP was determined at baseline in 147 of the patients and 7 days after bisphosphonate therapy in 73. Before ibandronate therapy, pCa was 3.36 +/- 0.02 mmol/L, mean TRCaI was increased at 3.09 +/- 0.03 mmol/L glomerular filtration rate (GFR; normal, 2.40-2.90), and 65% of patients had TRCaI above 2.90 mmol/L GFR. Mean serum PTHrP levels were 4.9 +/- 0.5 pmol/L (normal, <2.5) and values above the normal range were found in 53% of the patients (76% in lung and upper respiratory tract malignancies). By 7 days after the infusion of ibandronate, a decrease in pCa of 0.69 +/- 0.03 mmol/L (20.0 +/- 0.7%; P < 0.001) and in bone resorption [mean change in fasting urinary Ca, 0.09 +/- 0.04 mmol/L GFR (47.6 +/- 8.6%; P < 0.001) and 14.4 +/- 1.7 nmol/mmol (27.6 +/- 10.6%; P < 0.01) in deoxypyridinoline] was observed. TRCaI was slightly lowered by 0.30 +/- 0.09 mmol/L GFR. Mean changes in PTHrP, 1,25-dihydroxyvitamin D3, and PTH were +0.7 +/- 0.4 (P = NS), +27.6 +/- 3.0 (P < 0.001), and +2.9 +/- 0.8 (P < 0.005) pmol/L, respectively. After ibandronate treatment, the relative risk of relapsing hypercalcemia was particularly increased (3.43-fold) in lung and upper respiratory tract malignancies. These results obtained in a large cohort of patients indicate a significant prevalence of an increased renal tubular reabsorption of calcium index in hypercalcemia of malignancy and a substantial proportion of patients with detectable PTHrP.

Absorption↗
PubMed1998

Randomised controlled trial of effects of early discharge after surgery for breast cancer.

OBJECTIVE: To determine the effect of early discharge from hospital after surgery for breast cancer on physical and psychological illness. DESIGN: Randomised controlled trial comparing discharge two days after surgery (before removal of drain) with standard management (discharge after removal of drain). SETTING: Regional breast unit. SUBJECTS: 100 women with early breast cancer undergoing mastectomy and axillary node clearance (20) or breast conservation surgery (80). MAIN OUTCOME MEASURES: Physical illness (infection, seroma formation, shoulder movement) and psychological illness (checklist of concerns, Rotterdam symptom questionnaire, hospital anxiety and depression scale) preoperatively and at one month and three months postoperatively. RESULTS: Women discharged early had greater shoulder movement (odds ratio 0.28 (95% confidence interval 0.08 to 0.95); P = 0.042) and less wound pain (odds ratio 0.28 (0.10 to 0.79); P = 0.016) three months after surgery compared with women given standard management. One month after surgery scores were significantly lower on the Rotterdam symptom questionnaire in patients who were discharged early (ratio of geometric mean scores 0.73 (0.55 to 0.98) P = 0.035), but rates of psychological illness generally did not differ between groups. CONCLUSIONS: Increased rates of physical or psychological illness did not result from early discharge after surgery for breast cancer. This policy can be recommended for patients with support at home.

Adult↗
PubMed1997

Radioimmunoassay for serum apolipoprotein D, an atypical apolipoprotein: validation and clinical application.

Apolipoprotein D (apoD) is an atypical apolipoprotein in terms of its structure, synthesis and probable function. It is the most abundant protein in breast cyst fluids of patients suffering from macrocystic disease of the breast, a disease associated with an increased risk of developing breast cancer. We have developed and optimized a competitive radioimmunoassay for the measurement of apoD in human serum. The assay uses a solid phase separation method and with a 4 h incubation period, it can be completed in a single working day. The within and between run coefficients of variation were < 8.5% and < 12.2%, respectively, and quantitative recovery of apoD was obtained over the range 250-5000 micrograms/L. There was no difference in the serum concentrations of apoD between female controls, patients with benign breast disease and early breast cancer. However, serum apoD was significantly lower in breast cancer patients with bone metastasis.

Apolipoproteins↗
PubMed1995

Hypercalcemia and bone resorption in malignancy.

Hypercalcemia is the most common paraneoplastic syndrome associated with cancer. This paper addresses the etiology and pathogenesis of hypercalcemia of malignancy and discusses the relative contributions of local and humoral effects on bone and renal calcium homeostasis. The roles of parathyroid hormone-related protein and other osteolytic cytokines are outlined. New biochemical markers that enable more specific monitoring of the response of bone metastases to treatment are introduced, including urinary excretion of the collagen crosslinks pyridinoline and deoxypyridinoline. The clinical management and prevention of hypercalcemia is systemically outlined, including indications for bisphosphonate, glucocorticoid, and calcitonin therapy. The results of recent trials of bisphosphonate therapy for the prevention of tumor progression and its subsequent problems such as bone pain, fracture, and hypercalcemia also are discussed.

Animals↗
PubMed1987

Preliminary results using computerized telediaphanography for investigating breast disease.

An instrument (telediaphanograph) for examination of the female breast has been developed which is optically based and carries no risk to the patient. Malignant lesions, which are strongly light absorbing, can be visualized by dark shadows cast on the superior aspect of the breast. The discriminating ability of telediaphanography for carcinoma has been investigated in relation to 129 patients with suspected breast disease. The sensitivity was found to be 0.94 and the specificity 0.89.

Breast Diseases↗
PubMed1985

Acute pancreatitis in association with small cell lung carcinoma: potential pitfall in diagnosis and management.

Tumour metastases to the pancreas are a rare but recognized cause of acute pancreatitis, there is a 24-40% incidence of pancreatic involvement from small cell lung cancer in autopsy series but only a very few cases of tumour-induced acute pancreatitis have been described. Chemotherapy has been advocated as the primary therapy in patients with known oat cell carcinoma who develop acute pancreatitis. We describe 2 patients with acute haemorrhagic pancreatitis in association with disseminated small cell carcinoma but without evidence of tumour invasion in the gland and with gall stones present in the gall bladder. Chemotherapy would have been inappropriate therapy for these patients.

Acute Disease↗
PubMedDate not supplied

Prognostic significance of TGF beta 1 and TGF beta 3 in human breast carcinoma.

Transforming growth factor beta s (TGF beta s) are multifunctional growth factors which show differential expression both temporally and spatially and exert pleiotropic effects during carcinogenesis. Although all three mammalian isoforms of TGF beta share considerable sequence similarity, they appear to have distinct functions in health and disease, such as embryogenesis, wound healing and tumourigenesis. Much of our knowledge about the relationship between TGF beta s and breast cancer is based on publications on TGF beta 1 but the role of TGF beta 3 in the progression of breast cancer has not been well documented. In the present study, the expression of TGF beta 1 and TGF beta 3 was assessed by immunohistochemistry. Of the 153 invasive breast cancer tissues, TGF beta 1 was expressed strongly in 25 and moderately in 98 cases. The immunoreactivity of TGF beta 3 was comparable with TGF beta 1, which was expressed strongly in 21 and moderately in 104 cases. The two isoforms were coexpressed in 111 (72.5%) tumours and were absent in 16 cases (10%). Immunostaining for TGFb3 but not TGF beta 1 was inversely correlated with overall survival (p = 0.0204). When combined with lymph node involvement, TGFb3 became an even more significant prognostic factor for overall survival (p = 0.0003), i.e. patients with node metastasis and positive TGFb3 expression had a worse prognosis: the risk of death for these patients was thirteen-fold greater than those who had no node involvement. The fact that it has been reported previously that high TGF beta 3 plasma levels in patients with untreated early stage breast cancer were correlated with subsequent lymph node metastasis and it was observed in the present study too, that TGF beta 3 expression in breast tumours was an independent predictor of overall survival, led us to suggest that the simultaneous measurement of TGF beta 3 in plasma and its expression in resected tumour tissues in the same cohort of patients may prove to be an important parameter in assessing tumour progression.

Adult↗