Search PubMed⌕ Search

Biomedical subjects

N O'Higgins

Publications and source records attributed to N O'Higgins.

At least 19 recordsLinked to original sources
PubMed2003

Objective measurement of breast cancer oestrogen receptor status through digital image analysis.

AIMS: The authors have previously described quantitative, computer-assisted analysis of oestrogen receptor status in immuno-histochemically stained sections in patients with primary breast cancer. The aim of this study was to validate the aforementioned system against the commonly used methods of assessing oestrogen receptor status. METHODS: Paraffin embedded sections from 156 patients with primary breast carcinoma were stained with anti-alpha-oestrogen receptor monoclonal antibody (1D5) using a standard immunohistochemical protocol. Images from 10 high-powered fields were captured from each section using a digital camera mounted on a microscope and analyzed using Adobe Photoshop image analysis software. A nuclear mask was obtained by digitally selecting the nuclear area. Staining intensity in the nuclear mask was then analyzed using red-scale absorption characteristics. Manual assessment of oestrogen receptor status was performed through counting the percentages of cells that are positive from 200 randomly sampled nuclei from ten high powered fields HPF. Cut off value for positivity was taken as 10%. Cytosolic oestrogen receptor concentration was measured through enzyme immunisation. Cut off value for ER positivity was taken as 200 fmol/g (wet tissue). RESULTS: One hundred and fifty-six sections were studied of which 41 were ER negative. Median percentage positivity in the remainder was 90% (17-100) by manual assessment. The median red scale value was 108 (58-156). A close correlation was observed between median optical density of the nuclear mask and percentage positivity assessed manually (P<0.0001). There was a significant correlation between the optical density of the nuclear mask and cytosolic oestrogen receptor concentration (P<0.001). CONCLUSION: Oestrogen receptor positivity can be accurately assessed through digital image analysis. This process offers objective data regarding the amount of oestrogen receptors within the nuclei as well as the percentage of nuclei, which express oestrogen receptors.

Adult↗
PubMed2003

Predictive testing for BRCA1 and 2 mutations: a male contribution.

BACKGROUND: Management strategies for women carrying BRCA1 and 2 mutations are becoming clearer and predictive testing for a known family mutation is commonly undertaken. Implications for men are not as clear and they participate less frequently. PATIENTS AND METHODS: Twenty-six men from 10 extended families underwent predictive testing. Their motivation, reaction and outcome were studied. Subjects had appropriate pre- and post-test counselling. Informed consent was obtained before predictive testing for known deleterious mutations. DNA analysis followed standard procedures. RESULTS: Eighteen tested positive and eight negative. Four had adverse psychological reactions and three reneged on their commitments to impart results. The spouse of another man had an adverse psychological reaction to the disclosure of his positive result. Two, already suffering from prostate cancer, were phenocopies and paternal lineage transmission was unexpectedly determined in another. Risk was removed from 33 offspring and confirmed for 56. CONCLUSIONS: Complex themes associated with genetic testing are confirmed and the spectrum extended. Men appear to understand the importance of participating in this process. Methods of avoiding adverse reactions merit further study along with other aspects of the process.

Adult↗
PubMed2002

Pregnancy-associated breast cancer.

Twelve premenopausal women diagnosed with pregnancy-associated breast cancer between May 1985 and October 1999 were reviewed. Three patients were diagnosed in the first trimester of pregnancy, five in the second trimester, and three during the third trimester. There was one patient who was five weeks postpartum. At the time of diagnosis nine patients had lymph node involvement and two of these had metastatic disease. Four patients received primary chemotherapy. The remainder had surgery. Five patients died, two had metastatic disease at time of diagnosis, median survival was 31 months. There were three fetal deaths, one termination and two during primary chemotherapy. The diagnosis of breast cancer during pregnancy is difficult. Presentation is usually at an advanced stage. Surgery can be safely performed during pregnancy and adjuvant chemotherapy should not be postponed until after delivery.

Adult↗
PubMed2002

Parathyroid localisation--current practice.

In patients with primary hyperparathyroidism, neck exploration by an experienced parathyroid surgeon is curative in excess of 95% of cases. Considerable efforts have been devoted to improving parathyroid imaging. New radionucleotide agents and scanning procedures have markedly improved the success rate of localization studies with subsequent development of minimally invasive surgical techniques. In this article we review the different localization techniques and their current role in parathyroid surgery for primary hyperparathyroidism

Humans↗
PubMed2001

The European Society of Surgical Oncology.

Surgery is the key to local tumor control and survival in the vast majority of cancer patients. Optimally performed oncological operations, based both on a profound knowledge of the disease and on organ-based technical expertise are therefore essential. In this field the multinational European Society of Surgical Oncology (ESSO) wants to play a pivotal role, improving surgical treatment and encouraging and promoting education and training in surgical oncology at all levels. To achieve this goal the ESSO is of the opinion that recognition of surgical oncology as a separate subspecialty has to pursued.

Accreditation↗
PubMed2001

Evolving structures in surgical oncology and the role of the Federation of European Cancer Societies in continuing medical education.

This article describes the evolution of a European system of accreditation of educational events in oncology and the establishment by the Federation of European Cancer Societies of the Accreditation Council of Oncology in Europe. It draws attention to the need for a coordinated system which is acceptable in the different European countries so that an international system of "Eurocredits" can be devised. Through the official Union Europeénne des Médecins Specialistes (UEMS), reciprocity with the accrediting bodies in the United States and other countries is planned.

Accreditation↗
PubMed2000

Metalloproteinases: role in breast carcinogenesis, invasion and metastasis.

The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. Their primary function is degradation of proteins in the extracellular matrix. Currently, at least 19 members of this family are known to exist. Based on substrate specificity and domain organization, the MMPs can be loosely divided into four main groups: the interstitial collagenases, gelatinases, stromelysins and membrane-type MMPs. Recent data from model systems suggest that MMPs are involved in breast cancer initiation, invasion and metastasis. Consistent with their role in breast cancer progression, high levels of at least two MMPs (MMP-2 and stromelysin-3) have been found to correlate with poor prognosis in patients with breast cancer. Because MMPs are apparently involved in breast cancer initiation and dissemination, inhibition of these proteinases may be of value both in preventing breast cancer and in blocking metastasis of established tumours

Apoptosis↗
PubMed2000

Increased gelatinase-A and gelatinase-B activities in malignant vs. benign breast tumors.

Matrix metalloproteinases (MMP) types 2 and 9 (also known as gelatinase A and B) are thought to be causally involved in cancer invasion and metastasis. In normal as well as in malignant tissue, both these MMPs occur in multiple forms such as inactive precursors, active enzymes and enzyme-inhibitor complexes. Using newly developed quantitative activity assays, the levels of active MMP-2, total (active and activatable) MMP-2 and total MMP-9 were found to be significantly higher in breast carcinomas than in fibroadenomas. In addition, active MMP-2 and MMP-9 were detected more frequently in malignant than in benign breast carcinoma. These new quantitative activity assays are likely to be of use in studying the mechanism of action of both MMP-2 and -9, assessing their potential prognostic value in different cancers and in the design of MMP inhibitors for preventing cancer metastasis.

Breast Neoplasms↗
PubMed2000

High levels of TIMP-2 correlate with adverse prognosis in breast cancer.

TIMP-2 is an endogenous inhibitor of MMPs. Most data from model systems suggest that high levels of this inhibitor prevent metastasis. In human breast cancers, however, we show that high levels of TIMP-2 correlate with both shortened disease-free interval and overall survival. In primary breast cancers, TIMP-2 levels showed no significant relationship with either tumor size or axillary node status but correlated inversely with estrogen receptor levels. TIMP-2 levels also correlated significantly with those for TIMP-1. We conclude that high levels of endogenous TIMP-2, like other protease inhibitors such as PAI-1 and TIMP-1, correlate with progression of human breast cancer.

Biomarkers, Tumor↗
PubMed2000

A feasibility study evaluating docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer.

BACKGROUND AND PURPOSE: Docetaxel is an active agent in the treatment of metastatic breast cancer. We evaluated the feasibility of docetaxel-based sequential and combination regimens as adjuvant therapies for patients with node-positive breast cancer. PATIENTS AND METHODS: Three consecutive groups of patients with node-positive breast cancer or locally-advanced disease, aged < or = 70 years, received one of the following regimens: a) sequential A-->T-->CMF: doxorubicin 75 mg/m2 q 3 weeks x 3, followed by docetaxel 100 mg/m2 q 3 weeks x 3, followed by i.v. CMF days 1 + 8 q 4 weeks x 3; b) sequential accelerated A-->T-->CMF: A and T were administered at the same doses q 2 weeks; c) combination therapy: doxorubicin 50 mg/m2 + docetaxel 75 mg/m2 q 3 weeks x 4, followed by CMF x 4. When indicated, radiotherapy was administered during or after CMF, and tamoxifen started after the end of CMF. RESULTS: Seventy-nine patients have been treated. Median age was 48 years. A 30% rate of early treatment discontinuation was observed in patients receiving the sequential accelerated therapy (23% during A-->T), due principally to severe skin toxicity. Median relative dose-intensity was 100% in the three treatment arms. The incidence of G3-G4 major toxicities by treated patients, was as follows: skin toxicity a: 5%; b: 27%; c: 0%; stomatitis a: 20%; b: 20%; c: 3%. The incidence of neutropenic fever was a: 30%; b: 13%; c: 48%. After a median follow-up of 18 months, no late toxicity has been reported. CONCLUSIONS: The accelerated sequential A-->T-->CMF treatment is not feasible due to an excess of skin toxicity. The sequential non accelerated and the combination regimens are feasible and under evaluation in a phase III trial of adjuvant therapy.

Adult↗
PubMed1999

High levels of tissue inhibitor of metalloproteinase-1 predict poor outcome in patients with breast cancer.

Studies from model systems suggest that matrix metalloproteinases (MMPs) are causally involved in tumor progression while tissue inhibitors of MMPs (TIMPs) prevent this progression. Here, we show that concentrations of TIMP-1 are significantly higher in breast carcinomas than in fibroadenomas. In primary breast cancers, TIMP-1 concentrations increased with increasing tumor size but showed an inverse relationship with estrogen receptor concentrations. In primary breast cancers also, TIMP-1 levels were weakly but significantly correlated with those for MMP-1, proMMP-2, active MMP-2, MMP-3 and proMMP-9. Contrary to what might be expected from published data on model systems, high concentrations of TIMP-1 predicted a poor outcome in patients with breast cancer. We conclude that in human breast cancer, endogenous TIMP-1 does not inhibit tumor progression but may enhance the process.

Biomarkers, Tumor↗
PubMed1999

Urokinase plasminogen activator: a prognostic marker in multiple types of cancer.

Urokinase plasminogen activator (uPA) is a serine protease causally involved in cancer invasion and metastasis. Consistent with its role in cancer spread, uPA has been shown to be a prognostic marker in a variety of malignancies, especially breast cancer. Approximately 20 different groups have shown that high levels of uPA in breast tumor tissue predict poor outcome. As a prognostic marker in breast cancer, uPA provides information that is independent of traditionally used factors such as tumor size, tumor grade, axillary node status and estrogen receptor status. Furthermore, uPA is prognostic in node-negative patients, and a clinical trial is currently under way to assess whether uPA and its inhibitor, plasminogen activator inhibitor-1, can differentiate between the majority of node-negative breast cancer patients who are cured by surgery from the minority who might benefit from adjuvant therapy. uPA is also prognostic in other malignancies, such as gastric, colorectal, esophageal, renal, endometrial, and ovarian cancers. uPA may thus be a prognostic indicator for multiple types of adenocarcinoma.

Biomarkers, Tumor↗
PubMed1998

Letrozole, a new oral aromatase inhibitor: randomised trial comparing 2.5 mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Letrozole International Trial Group (AR/BC3).

BACKGROUND: The study compares letrozole and aminoglutethimide (AG), a standard therapy for postmenopausal women with advanced breast cancer, previously treated with antioestrogens. PATIENTS AND METHODS: 555 women were randomly assigned letrozole 2.5 mg once daily (n = 185), letrozole 0.5 mg once daily (n = 192) or aminoglutethimide 250 mg twice daily with corticosteroid support (n = 178) in an open-label, multicentre trial. The primary endpoint was objective response rate (ORR), with time events as secondary. ORR was analysed nine months after enrollment of the last patient, while survival was analysed 15 months after the last patient was enrolled. We report the results of these analyses plus an extended period of observation (covering a total duration of approximately 45 months) to determine the duration of response and clinical benefit. RESULTS: Overall objective response rates (complete + partial) of 19.5%, 16.7% and 12.4% were seen for letrozole 2.5 mg, 0.5 mg and AG respectively. Median duration of response and stable disease was longest for letrozole 2.5 mg (21 months) compared with letrozole 0.5 mg (18 months) and AG (14 months). Letrozole 2.5 mg was superior to AG in time to progression, time to treatment failure and overall survival. Treatment-related adverse events occurred in fewer patients on letrozole (33%) than on AG (46%). Transient nausea was the most frequent event with letrozole (7% on 0.5 mg, 10% on 2.5 mg, 10% on AG), rash with AG (11%, 1% on 0.5 mg, 3% on 2.5 mg letrozole). CONCLUSIONS: Letrozole 2.5 mg offers longer disease control than aminoglutethimide and letrozole 0.5 mg in the treatment of postmenopausal women with advanced breast cancer, previously treated with anti-oestrogens.

Administration, Oral↗
PubMed1998

Assay of matrix metalloproteinases types 1, 2, 3 and 9 in breast cancer.

Matrix metalloproteinases (MMPs) are zinc dependent endopeptidases implicated in cancer invasion and metastasis. Gelatin zymography was performed on 84 human breast carcinomas and seven normal breast tissues. The precursor form of MMP-2 (72 kDa) was found in 11 (12%) samples, while its two activated forms, i.e. 62 kDa and 59 kDa, were found in three (6%) and 34 (40%) samples respectively. In contrast to MMP-2, most of the samples (52%) contained MMP-9 in its precursor form. Using ELISA, MMP-1 levels were found in 12% of the samples while MMP-3 levels were found in only 2% of the samples. Levels of MMP-2, -3 and -9 correlated inversely with numbers of nodal metastases. Neither MMP-2 nor -9 levels were significantly related to patient outcome. However, patients with high levels of a 50-kDa gelatinase band after zymography had a significantly better survival than patients with low levels. This species was never observed in normal breast tissue.

Breast↗
PubMed1998

Principles and guidelines for surgeons--management of symptomatic breast cancer. On behalf of the European Society of Surgical Oncology.

The European Society of Surgical Oncology is actively involved in the promotion of a high standard of surgical oncology throughout Europe. Such an ambition involves recognition of Centres of Excellence in the management of cancer patients throughout Europe. These centres have a multi-disciplinary system involved in the total care of patients with cancer and are concerned with the delivery of care to the highest available standards. It is accepted that not all patients with cancer can, nor should, necessarily be treated in such highly specialized centres. Yet all cancer patients should be guaranteed a high standard of care. High surgical standards can be ensured if surgeons treating cancer are trained in specialist centres and, when in independent practice, follow established guidelines or protocols of treatment. In common with many national surgical oncology societies, the European Society of Surgical Oncology is in the process of establishing good practice guidelines in the treatment of solid tumours. This document on the management of symptomatic breast cancer is the first of a series of guidelines to be proposed by ESSO. It draws heavily on excellent documents already in existence from the British Association of Surgical Oncology and from the Danish Breast Cancer Co-Operative Group. It is hoped that this document will be sufficiently clear and purposeful to be of help to the individual surgeon and yet sufficiently flexible to allow it to be adopted in the different medical systems throughout Europe.

Breast Neoplasms↗
PubMed1998

European guidelines for quality assurance in the surgical management of mammographically detected lesions. European Breast Cancer Working Group.

The European Guidelines developed for mammography screening have contributed to the general discussion on quality assurance and the important tasks of the health professionals dealing with breast cancer screening. The cooperation of each medical discipline is of utmost importance in order to achieve optimal results and eventually a mortality reduction. The following guidelines are based on the British NHS quality assurance guidelines for surgeons in breast cancer screening and modified to meet the different needs in the European Countries. The term "surgeon" denotes a medical doctor trained and involved in the surgical treatment of breast diseases. The members of the working group who participated in order to adapt these guidelines are listed above. We hope that this document will contribute towards a more comprehensive approach of breast cancer screening-detected lesions throughout Europe.

Breast Neoplasms↗