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Nigel Bundred

Publications and source records attributed to Nigel Bundred.

13 recordsLinked to original sources
PubMed2006

Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial.

BACKGROUND: Sentinel lymph node biopsy in women with operable breast cancer is routinely used in some countries for staging the axilla despite limited data from randomized trials on morbidity and mortality outcomes. We conducted a multicenter randomized trial to compare quality-of-life outcomes between patients with clinically node-negative invasive breast cancer who received sentinel lymph node biopsy and patients who received standard axillary treatment. METHODS: The primary outcome measures were arm and shoulder morbidity and quality of life. From November 1999 to October 2003, 1031 patients were randomly assigned to undergo sentinel lymph node biopsy (n = 515) or standard axillary surgery (n = 516). Patients with sentinel lymph node metastases proceeded to delayed axillary clearance or received axillary radiotherapy (depending on the protocol at the treating institution). Intention-to-treat analyses of data at 1, 3, 6, and 12 months after surgery are presented. All statistical tests were two-sided. RESULTS: The relative risks of any lymphedema and sensory loss for the sentinel lymph node biopsy group compared with the standard axillary treatment group at 12 months were 0.37 (95% confidence interval [CI] = 0.23 to 0.60; absolute rates: 5% versus 13%) and 0.37 (95% CI = 0.27 to 0.50; absolute rates: 11% versus 31%), respectively. Drain usage, length of hospital stay, and time to resumption of normal day-to-day activities after surgery were statistically significantly lower in the sentinel lymph node biopsy group (all P < .001), and axillary operative time was reduced (P = .055). Overall patient-recorded quality of life and arm functioning scores were statistically significantly better in the sentinel lymph node biopsy group throughout (all P < or = .003). These benefits were seen with no increase in anxiety levels in the sentinel lymph node biopsy group (P > .05). CONCLUSION: Sentinel lymph node biopsy is associated with reduced arm morbidity and better quality of life than standard axillary treatment and should be the treatment of choice for patients who have early-stage breast cancer with clinically negative nodes.

Arm↗
PubMed2005

Preclinical and clinical experience with fulvestrant (Faslodex) in postmenopausal women with hormone receptor-positive advanced breast cancer.

Fulvestrant (Faslodex) is a new type of estrogen receptor (ER) antagonist that binds, blocks, and degrades the ER, leading to reduced expression of the progesterone receptor (PgR). Unlike the selective ER modulator tamoxifen, fulvestrant is devoid of any known agonist activity. Fulvestrant has a steroidal structure that competitively binds to the ER with an affinity much greater than that of tamoxifen. After binding to fulvestrant, degradation of the ER is accelerated, ultimately resulting in a reduction in cellular ER. Immunohistochemical studies have demonstrated that a single intramuscular injection of fulvestrant results in a dose-dependent decrease in ER and PgR indices and in Ki-67 expression. At the approved 250 mg dose, the decrease in receptor positivity with fulvestrant treatment was greater than that with tamoxifen. Phase III clinical trials have demonstrated the clinical benefit of fulvestrant in the endocrine treatment of breast cancer. Among patients who progressed during adjuvant or first-line endocrine therapy, fulvestrant was at least as effective as anastrozole as second-line treatment for the primary endpoints of objective response and time to progression, and was well tolerated. After a median follow-up of 24.5 months, a combined survival analysis from two Phase III studies has shown that fulvestrant may be considered similar to anastrozole for time to death (27.4 months versus 27.7 months, respectively). For the first-line therapy of advanced breast cancer in postmenopausal women, fulvestrant was shown to be active and well tolerated in a trial that compared fulvestrant 250 mg once monthly and tamoxifen 20 mg once daily. Treatment with fulvestrant has also demonstrated clinical efficacy among patients who progressed following treatment with tamoxifen followed by nonsteroidal aromatase inhibitors. The efficacy of fulvestrant in sequential endocrine therapy and in combination with other agents appears promising and active investigations are ongoing to explore the clinical potential of this novel antiestrogen.

Aged↗
PubMed2005

Breast pain.

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Breast↗
PubMed2005

Breast pain.

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Breast↗
PubMed2004

Breast pain.

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Breast↗
PubMed2003

Breast pain.

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Breast↗
PubMed2002

Activation of BAD by therapeutic inhibition of epidermal growth factor receptor and transactivation by insulin-like growth factor receptor.

Novel cancer chemotherapeutics are required to induce apoptosis by activating pro-apoptotic proteins. Both epidermal growth factor (EGF) and insulin-like growth factor (IGF) provide potent survival stimuli in many epithelia, and activation of their receptors is commonly observed in solid human tumors. Here we demonstrate that blockade of the EGF receptor by a new drug in phase III clinical trails for cancer, ZD1839, potently induces apoptosis in mammary epithelial cell lines and primary cultures, as well as in a primary pleural effusion from a breast cancer patient. We identified the mechanism of apoptosis induction by ZD1839. We showed that it prevents cell survival by activating the pro-apoptotic protein BAD. Moreover, we demonstrate that IGF transactivates the EGF receptor and that ZD1839 blocks IGF-mediated phosphorylation of MAPK and BAD. Many cancer therapies kill tumor cells by inducing apoptosis as a consequence of targeting DNA; however, the threshold at which apoptosis can be triggered through DNA damage is often different from that in normal cells. Our results indicate that by targeting a growth factor-mediated survival signaling pathway, BAD phosphorylation can be manipulated therapeutically to induce apoptosis.

Animals↗
PubMed2002

Costs and benefits of a one stop clinic compared with a dedicated breast clinic: randomised controlled trial.

OBJECTIVE: To determine the cost to the NHS and the impact on anxiety of a one stop clinic for assessing women with suspected breast cancer. STUDY DESIGN: Randomised controlled trial. PARTICIPANTS: Women aged 35 or over referred with a breast lump. STUDY SETTING: Teaching hospital, north west England. INTERVENTIONS: Women were randomly allocated to attend a one stop clinic or a dedicated breast clinic. OUTCOME MEASURES: Reduction in mean anxiety from baseline at 24 hours after the first visit and at 3 weeks and 3 months after diagnosis; mean cost per patient. RESULTS: 670 women were randomised. Compared with women who attended the dedicated clinic, patients attending the one stop clinic were less anxious 24 hours after the visit (adjusted mean change in state anxiety _5.7 (95% confidence interval _8.4 to _3.0)) but not at 3 weeks or 3 months after diagnosis. The additional cost to the NHS of a one stop attendance was pound 32 per woman; this was largely explained by greater cytopathological and radiological staff costs. CONCLUSION: One stop clinics may not be justified in terms of a reduction in short term anxiety.

Adult↗
PubMed2002

Fulvestrant (Faslodex): current status in the therapy of breast cancer.

Fulvestrant (Faslodex, formerly ICI 182,780) is a potent steroidal antiestrogen that mediates its effects by estrogen receptor downregulation. It appears to act as a pure antiestrogen and exhibits none of the negative side effects associated with the partial agonist activity of tamoxifen. It has been shown to be as effective as the oral aromatase inhibitor anastrozole in postmenopausal women with advanced breast cancer who have progressed on prior endocrine therapy, principally tamoxifen. It therefore provides the clinician with an alternative therapeutic strategy following the development of tamoxifen resistance. Fulvestrant might also have potential as a follow-on therapy after tamoxifen in an adjuvant setting and help alleviate some of the concerns surrounding long-term (up to 5 years) tamoxifen therapy.

Animals↗
PubMed2002

Breast pain.

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Breast↗
PubMed2002

Coexpression of parathyroid hormone related protein and its receptor in early breast cancer predicts poor patient survival.

PURPOSE: Parathyroid hormone-related protein (PTHRP) is in part responsible for the clinical syndrome of hypercalcaemia of malignancy and has been implicated as an important factor in the development of bone metastases. The aim of this study was to determine the coexpression of PTHRP and its receptor in early breast cancer (EBC) and bone metastases (BM), and correlate these findings to clinical outcome. EXPERIMENTAL DESIGN: Samples of surgically excised EBC (n = 176) and BM (n = 43) were collected and stored in liquid nitrogen. PTHRP protein was determined using immunohistochemistry and receptor mRNA using in situ hybridization (n = 107) or semiquantitative reverse transcription-PCR (n = 69). RESULTS: PTHRP protein was expressed in 115 of 170 (68%) EBC compared with 100% of BM (P < 0.001), whereas its receptor mRNA was expressed in 88 of 176 (50%) EBC compared with 35 of 43 (81%) BM (P < 0.001). Coexpression of both PTHRP and its receptor was present in 62 EBC samples (37%) and in 35 BM samples (81%; P < 0.001). The PTHRP receptor correlated well with increasing patient age, but not with tumor size, grade, estrogen receptor, progesterone receptor, or lymph node status. Individually PTHRP and PTHRP receptor both correlated well with a reduced disease-free survival (P < 0.004) and receptor alone with reduced overall survival (P < 0.003). Coexpression of both PTHRP and receptor predicted the worst clinical outcome at 5 years, with a mortality rate of 20 of 62 (32%) compared with the ligand and receptor-negative group with 2 of 32 (6%; P < 0.004). CONCLUSIONS: Overall these results show that the PTHRP receptor is expressed more frequently in BM than EBC, and is associated with poor clinical outcome and survival.

Aged↗
PubMed2002

Breast pain.

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Breast↗