Nottingham Prognostic Index Plus: Validation of a clinical decision making tool in breast cancer in an independent series.

The Nottingham Prognostic Index Plus (NPI+) is a clinical decision making tool in breast cancer (BC) that aims to provide improved patient outcome stratification superior to the traditional NPI. This study aimed to validate the NPI+ in an independent series of BC. Eight hundred and eighty five primary early stage BC cases from Edinburgh were semi-quantitatively assessed for 10 biomarkers [Estrogen Receptor (ER), Progesterone Receptor (PgR), cytokeratin (CK) 5/6, CK7/8, epidermal growth factor receptor (EGFR), HER2, HER3, HER4, p53, and Mucin 1] using immunohistochemistry and classified into biological classes by fuzzy logic-derived algorithms previously developed in the Nottingham series.

GSK3β and cyclin D1 expression predicts outcome in early breast cancer patients.

Glycogen synthase kinase 3β (GSK3β) is phosphorylated and inactivated by the phosphoinositide 3 kinase PI3K/Akt pathway. Activation of Akt phosphorylates GSK3β preventing phosphorylation of cyclin D1 which leads to accumulation and nuclear localisation of cyclin D1, activation of CDK4/6 and cell cycle progression. The CCND1 gene found at chromosome 11q13 has been shown to be amplified in approximately 15 % of breast cancers.

Expression of activated type I receptor tyrosine kinases in early breast cancer.

Overexpression of EGFR, HER2 and HER3 are known to be associated with poor outcome in breast cancer. Few studies have examined the clinical impact of activation of these proteins. In the present study, we evaluated EGFR, HER2 and HER3 and the activated (phosphorylated) forms of these proteins in patients with early breast cancer.

Proximity ligation assays for isoform-specific Akt activation in breast cancer identify activated Akt1 as a driver of progression.

The PI3K/Akt signal transduction pathway plays an important role in cancer progression and cell survival. Akt activation is associated with poor outcome in endocrine-treated breast cancer, whereas high levels of cytoplasmic Akt2 are associated with an improved overall survival. Proximity ligation assays (PLAs) were used to determine quantitative expression levels of isoform-specific activation (phosphorylation) of Akt1 and Akt2 in formalin-fixed, paraffin-embedded cell lines and breast cancer tumour tissues in situ.

Impact of screening and risk factors for local recurrence and survival after conservative surgery and radiotherapy for early breast cancer: results from a large series with long-term follow-up.

Purpose: To investigate conventional prognostic factors for ipsilateral breast tumor recurrence (IBTR), distant metastasis (DM), and survival after breast-conserving therapy (BCT) in screen-detected and symptomatic cases on surveillance up to 25 years.

Patients And Methods: A total of 1812 consecutive patients in three cohorts (1981-1989, 1990-1992, and 1993-1998) with T12N01M0 invasive breast cancer were treated with BCT (median follow-up, 14 years). Tumor type and grade were reviewed by a single pathologist.

Mammostrat as a tool to stratify breast cancer patients at risk of recurrence during endocrine therapy.

Introduction: Patients with early-stage breast cancer, treated with endocrine therapy, have approximately 90% 5-year disease-free survival. However, for patients at higher risk of relapse despite endocrine therapy, additional adjuvant therapy, such as chemotherapy, may be indicated. The challenge is to prospectively identify such patients.

Radiotherapy for pituitary adenomas: long-term efficacy and toxicity.

Background: Radiotherapy for pituitary adenomas is an effective treatment but remains controversial due to toxicity concerns.

Materials And Methods: A retrospective audit of patients referred for radiotherapy during 1974-2003 was conducted, the case records were examined and data linkage to cancer registry and hospital discharge records was performed to assess the overall survival (OS), progression-free survival (PFS) and late effects (hormone deficiency, reduced vision, second cancer and stroke).

Results: Three hundred and eighty-five patients had radiotherapy (median 45 Gy).

Histological grading of invasive breast carcinoma--a simplification of existing methods in a large conservation series with long-term follow-up.

Aims: To assess the validity of grading in the Edinburgh Breast Conservation Series; a consecutive cohort of 1812 early breast cancer patients treated by breast conservation and radiotherapy between 1981 and 1998 in a single specialist centre with > or =9 years' follow-up and full staging data.

Methods And Results: A single pathologist (J.St.

Increase in response rate by prolonged treatment with neoadjuvant letrozole.

Purpose: The aim of this study was to investigate the potential benefits of prolonged treatment with neoadjuvant letrozole.

Patients And Methods: About 182 consecutive patients have been treated in Edinburgh with neoadjuvant letrozole for 3 months or longer and 63 patients have continued on letrozole beyond 3 months. Outcomes are reported.

Incidence of sarcoma in patients treated with fast neutrons.

Purpose: The aim of this study is to report the incidence of soft tissue sarcoma in a large group of patients treated with fast neutrons.

Methods: A systematic review was conducted of long-term follow-up after trials of fast neutron therapy for cancers at various sites. The study took place at Edinburgh Cancer Centre, Western General Hospital, Edinburgh, Scotland, United Kingdom.

Outcome analysis of 300 prostate cancer patients treated with neoadjuvant androgen deprivation and hypofractionated radiotherapy.

Purpose: Neoadjuvant androgen deprivation and radical radiotherapy is an established treatment for localized prostate carcinoma. This study sought to analyze the outcomes of patients treated with relatively low-dose hypofractionated radiotherapy.

Methods And Materials: Three hundred patients with T1-T3 prostate cancer were treated between 1996 and 2001.

The effect of overall treatment time on the survival and toxicity of radical radiotherapy for cervical carcinoma.

Background And Purpose: Overall treatment time is an important factor in the outcome of radical radiotherapy in head and neck, bladder and lung cancer and in cervix cancer treated over more than 7 weeks. This study analysed the effect of prolongation of overall treatment time on survival and late morbidity for patients receiving radical radiotherapy for cervical cancer treated with a 4-week regimen.

Materials And Methods: Using the departmental SAS data-base we identified all patients with cervix cancer treated between 1974 and 1988 and investigated the 647 patients who received 20 fractions of external beam radiotherapy plus intracavitary therapy with a total dose to point A of at least 60Gy.