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Biomedical subjects

R W Blamey

Publications and source records attributed to R W Blamey.

At least 19 recordsLinked to original sources
PubMed2006

EUSOMA accreditation of breast units.

EUSOMA (European Society of Mastology) is the organisation representing Breast Cancer Specialists in all disciplines, covering all aspects of breast cancer from risk and prevention, through diagnosis and treatment of the primary tumour, follow-up, treatment of recurrent and advanced disease, pathology, reconstruction, psychology and audit. EUSOMA Guidelines have been published on several aspects of breast cancer and are on service provision as well as giving clinical guidance and providing the basis for audit.

Accreditation↗
PubMed2005

Prognostic value of lymphovascular invasion in women with lymph node negative invasive breast carcinoma.

This study aimed to test the hypothesis that lymphovascular invasion adds prognostic information to histological grade and tumour size in node-negative invasive carcinoma of the breast. Lymphovascular invasion was assessed in haematoxylin and eosin tumour sections from 2760 patients with node-negative invasive breast carcinoma treated with definitive surgery. Patients were divided into two groups: 990 in the no adjuvant therapy series (diagnosed in 1974-1988) with median follow-up of 13 years; and 1765 in the selective adjuvant therapy series (1988-2000) with median follow-up of 6.8 years. Lymphovascular invasion was identified in 19% of tumours and was associated with larger tumour size, higher histological grade and younger age. Overall, survival was associated on multivariate analysis with lymphovascular invasion, histological grade and tumour size in both patient series, and with histological type in the no adjuvant therapy series. In conclusion, lymphovascular invasion is an independent prognostic factor in node-negative breast cancer and should be considered in decisions about adjuvant treatment in this group of women.

Adult↗
PubMed2004

Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma.

The epidermal growth factor receptor (EGFR) family plays an important role in breast carcinogenesis. Much interest has been focused recently on its members because of their potential role as prognostic indicators in breast cancer and their involvement in cancer therapy. We have evaluated more than 1500 cases of invasive breast carcinoma immunohistochemically using tissue microarray technology to examine the expression of EGFR family receptor proteins. We have found that 20.1 and 31.8% of cases were positive for EGFR and c-erbB-2, respectively, and 45 and 45.1% of tumours overexpressed for c-erbB-3 and c-erbB-4, respectively. The expression of either EGFR or c-erbB-2 was associated with other bad prognostic features and with poor outcome. Neither c-erbB-3 nor c-erbB-4 had any association with survival. c-erbB-2 had an independent prognostic effect on overall and disease-free survival (DFS) in all cases, as well as in the subset of breast carcinoma patients with nodal metastases. Several hetero- and homodimeric combinations have been reported between the EGFR members. Those dimers can evoke diverse signal transduction pathways with variable cellular responses. We stratified cases according to their co-expression of receptors into distinct groups with different receptor-positive combinations. Patients whose tumours co-expressed c-erbB-2 and c-erbB-3, as well as those whose tumours co-expressed EGFR, c-erbB-2 and c-erbB-4 showed an unfavourable outcome compared with other groups, while combined c-erbB-3 and c-erbB-4 expression was associated with a better outcome. In cases showing expression of one family member only (homodimers), we found a significant association between c-erbB-4 homodimer-expressing tumours and better DFS. In contrast, patients with c-erbB-2 homodimer-expressing tumours had a significant poorer DFS compared with other cases. These data imply that the combined profile expression patterns of the four receptor family members together provide more accurate information on the tumour behaviour than studying the expression of each receptor individually.

Adenocarcinoma↗
PubMed2004

Expression of luminal and basal cytokeratins in human breast carcinoma.

We have examined basal and luminal cell cytokeratin expression in 1944 cases of invasive breast carcinoma, using tissue microarray (TMA) technology, to determine the frequency of expression of each cytokeratin subtype, their relationships and prognostic relevance, if any. Expression was determined by immunocytochemistry staining using antibodies to the luminal cytokeratins (CKs) 7/8, 18 and 19 and the basal markers CK 5/6 and CK 14. Additionally, assessment of alpha-smooth muscle actin (SMA) and oestrogen receptor status (ER) was performed. The vast majority of the cases showed positivity for CK 7/8, 18 and 19 indicating a differentiated glandular phenotype, a finding associated with good prognosis, ER positivity and older patient age. In contrast, basal marker expression was significantly related to poor prognosis, ER negativity and younger patient age. Multivariate analysis showed that CK 5/6 was an independent indicator for relapse free interval. We were able to subgroup the cases into four distinct phenotype categories (pure luminal, mixed luminal/basal, pure basal and null), which had significant differences in relation to the biological features and the clinical course of the disease. Tumours classified as expressing a basal phenotype (the combined luminal plus basal and the pure basal) were in a poor prognostic subgroup, typically ER negative in most cases. These findings provide further evidence that breast cancer has distinct differentiation subclasses that have both biological and clinical relevance.

Actins↗
PubMed2004

Local anaesthetic and steroid combined injection therapy in the management of non-cyclical mastalgia.

AIMS: We aimed to assess the effectiveness of a local anaesthetic and steroid combination injection therapy in the management of non-cyclical mastalgia. METHODS: Patients with non-cyclical mastalgia were assessed for rib tenderness (lateral chest wall tenderness-LCWT). The tenderest spot was injected with a combined preparation of 1 ml 2% lignocaine and 1 ml 40 mg depomedrone. Those who declined injection therapy were advised on topical or oral NSAIDs or reassurance. All patients were reassessed 6 weeks later. A successful outcome was taken as either a complete response (CR) or partial response (PR), i.e. pain although present is tolerated. RESULTS: One hundred and thirty eight women were diagnosed with LCWT. One hundred and four women were injected. Thirty-four women declined and were managed appropriately. At assessment 83 injected cases were successful (83%; CR n = 61, PR n = 22) compared to 13 non-injected cases (44.8%; CR n = 5, PR n = 8, P < 0.0001). No side effects were recorded. Sixteen cases recurred and were successfully re-injected. CONCLUSIONS: A steroid and local anaesthetic injection is an effective and safe treatment for LCWT.

Adolescent↗
PubMed2004

Management of physiological gynaecomastia with tamoxifen.

AIMS: We aimed to confirm suggestions that tamoxifen therapy alone may resolve physiological gynaecomastia. METHODS: A prospective audit of the outcome of tamoxifen routinely given to men with physiological gynaecomastia was carried out at Nottingham. Men referred with gynaecomastia had clinical signs recorded, e.g., type (diffuse 'fatty' or retro-areolar 'lump'), size and possible aetiology. They were offered oral tamoxifen 20mg once daily for 6-12 weeks. On follow-up patients were assessed for complete resolution (CR), partial resolution where patient is satisfied with outcome (PR) or no resolution (NR). Success was either CR or PR. RESULTS: Thirty-six men accepted tamoxifen for physiological gynaecomastia. Median age was 31 (range 18-64). Tenderness was present in 25 (71%) cases. Sixteen men (45%) had 'fatty' gynaecomastia and 20 had 'lump' gynaecomastia. Tamoxifen resolved the mass in 30 patients (83.3%; CR=22, PR=8) and tenderness in 21 cases (84%; CR=0, PR=0). Lump gynaecomastia was more responsive to tamoxifen than the fatty type (100% vs. 62.5%; P=0.0041). CONCLUSIONS: Oral tamoxifen is an effective treatment for physiological gynaecomastia, especially for the lump type.

Administration, Oral↗
PubMed2004

Woman feels breast lump--surgeon cannot: the role of ultrasound in arbitration.

The role of ultrasound scanning (USS) in patients complaining of a breast lump where the clinical examination (CE) is normal is not clearly defined. To determine this in greater detail, all patients complaining of a breast lump underwent CE. Where no lump could be found, but was still reported by the patient, an USS was performed. All lesions underwent biopsy and/or aspiration, as well as mammography in suspicious cases or those over 40 years of age. This cohort represented 5% of all referrals in the study period. Four hundred and twenty women were prospectively studied in this way. Median follow up is 3.4 years (range 2.5-4.2 years). Twenty two had solid lumps (of which 3 were cancers) and 48 had cysts. Nineteen patients re-presented with symptoms in the same breast (median time = 12 months (range 4.5-20 months), all of which were imaged on USS: 15 cysts and 4 further cancers (3 in the same quadrant as the original lump, one contralateral) were identified. Women with symptomatic breast lumps and a normal CE can be considered a reliable indication that cancer is very unlikely to be present (negative predictive value = 0.98). Ultrasound may be a suitable complimentary investigation, which will relieve symptoms in those with cysts and can detect small clinically--and sometimes mammographically--occult breast cancers.

Adolescent↗
PubMed2004

Are medullary breast cancers an indication for BRCA1 mutation screening? A mutation analysis of 42 cases of medullary breast cancer.

Recommended guidelines have limited breast cancer gene ( BRCA1 ) mutation testing to individuals with a personal or family history of early onset breast and/or ovarian cancer, and those with multiple affected close relatives. Such large breast cancer families are rare in the general population, limiting the clinical application of the BRCA1 discovery. Previous reports have suggested an association between medullary breast cancer and BRCA1 mutation carriers. To test the feasibility of using these rare histological subtypes as an alternative to epidemiological factors, 42 cases of medullary cancer unselected for family history were screened for BRCA1 point mutations and large exon rearrangements. The large majority (83%) of these patients did not have significant family of breast or ovarian cancer. Two deleterious mutations resulting in a premature stop codon, and one exon 13 duplication were found. All mutations were detected in patients with typical medullary cancer, who had family history of multiple breast and ovarian cancers. Our findings suggest that medullary breast cancers are not an indication for BRCA1 mutation screening in the absence of significant family risk factors.

Breast Neoplasms↗
PubMed2004

Phenotypic similarities in bilateral breast cancer.

Bilateral breast cancers that develop at similar times in an individual are likely to have been subjected to similar hormonal, environmental and genetic influences during tumourogenesis compared with metachronous tumours. As such, it is possible that tumour phenotype in synchronous bilateral breast cancer may display similar biological characteristics. The aim of this study was to identify phenotypic similarities between synchronous and metachronous bilateral breast cancers which may suggest a common origin. Thirty-three cases of synchronous and 46 cases of metachronous bilateral breast cancer that displayed similar tumour type were analysed for concordance in relation to various histological and immunohistochemical parameters. A higher level of concordance was demonstrated for synchronous cases with the highest level seen for oestrogen receptor. It is likely that this is related to similar tumourogenic pathways occurring at equivalent exposure times to various environmental and hormonal influences, although, in a proportion of cases, inherited genetic factors may play a role.

Adult↗
PubMed2003

The use of gonadotrophin-releasing hormone (GnRH) agonists in early and advanced breast cancer in pre- and perimenopausal women.

Gonadotrophin-releasing hormone (GnRH) agonists, in particular goserelin ('Zoladex'), are increasingly being used for the treatment of breast cancer in women with functioning ovaries. They act by downregulating pituitary GnRH receptors, thereby suppressing the release of luteinising hormone (LH) and follicle stimulating hormone (FSH), which, in turn, reduce the main source of oestradiol production in the ovaries. GnRH agonists have been shown to be as effective therapeutically as surgical ovarian ablation in pre- and perimenopausal women with advanced breast cancer. The combination of a GnRH agonist such as goserelin with the peripheral oestrogen antagonist, tamoxifen, may be used to produce 'combined oestrogen blockade'. In advanced breast cancer, this regimen prolongs progression-free survival and increases both the response rate and duration relative to the use of a GnRH agonist alone. In patients with early breast cancer, the addition of goserelin to 'standard treatment' (i.e. surgery+/-tamoxifen, chemotherapy or radiotherapy) results in a significant benefit in recurrence-free survival and overall survival. This benefit was most apparent in patients with oestrogen receptor (ER) +ve tumours. Goserelin, when used either alone or in combination with tamoxifen as an adjuvant systemic therapy in women with ER +ve tumours, has been shown in clinical trials to produce recurrence-free survival rates equivalent to cytotoxic chemotherapy such as cyclophosphamide, methotrexate, 5-fluorouracil (CMF). Evidence suggests that at least part of the effect of adjuvant cytotoxic chemotherapy in premenopausal women is produced by ovarian ablation. Endocrine therapy with goserelin or goserelin plus tamoxifen should now be considered a treatment option in the management of premenopausal women with ER +ve early breast cancer.

Amenorrhea↗
PubMed2003

Incidence of clinically significant lymphoedema as a complication following surgery for primary operable breast cancer.

There has recently been considerable interest for the need for specialist lymphoedema nurses to be appointed in the NHS. However, we had noticed in our cancer follow-up clinics that the incidence of lymphoedema appeared to be very low. Treatment for primary breast cancer (>5 cm) has been surgery and low axillary sampling (ANS). Radiotherapy (RT) or axillary clearance is subsequently performed in patients found to be node positive. The patients are followed-up in the primary breast cancer (PBC) clinic weekly. Follow-up is initially at 3-month intervals up to 2 years and then 1 yearly indefinitely. We conducted a two phased study in patients being followed up in our post cancer clinic in order to identify the incidence of LE in these patients. Phase 1 involved symptomatic patients identified at routine follow up in a 15-week period and the number of patients reporting arm swelling was recorded. The aim of this was to provide an estimate to power a phase 2 study (prospective questionnaire based). Phase 2 was conducted over a 13-week period. All patients attending the clinic were administered modified FACT B4, EQ-50 and Speilberger questionnaires. A total of 1242 patients were examined and lymphoedema found in 5 (0.04%). Of these 5, 3 had undergone axillary clearance, 1 ANS plus radiotherapy and only 1 had ANS alone. A policy of ANS, with prophylactic treatment for lymph node positivity either by surgery or RT alone, gives a very low rate of lymphoedema.

Arm↗
PubMed2002

Postoperative radiotherapy following mastectomy for high-risk breast cancer. A randomised trial.

Grade III, node-positive breast cancer carries a high risk of loco-regional relapse after simple mastectomy. A randomised trial was conducted to assess whether this would be significantly reduced by postoperative radiotherapy. Between 1985 and 1991, 76 patients who had undergone a simple mastectomy and axillary sampling, and whose tumours had been found to be grade III and node-positive, were randomised to receive postoperative radiotherapy to the chest wall and axilla or no further loco-regional treatment. Radiotherapy was delivered with 8 MV X-rays to the axilla and supraclavicular fossa and with 8 MeV electrons to the chest wall, to a dose of 45 Gy in 15 fractions over 3 weeks. All patients have been followed-up until death, or for a minimum of 10 years. All loco-regional recurrences occurred within the first 4 years after mastectomy. There were 26 such events in the 40 patients randomised to the 'watch' policy (65%), as opposed to 9 out of 36 (25%) who received radiotherapy (P<0.01). Ten-year survival was 39% in the radiotherapy arm as opposed to 25% in the no radiotherapy arm. Recruitment to the trial was closed in 1991, when a preliminary safety analysis revealed the size of the effect of radiotherapy, and from then on all node-positive patients with grade III tumours have routinely been given this treatment. Further follow-up has confirmed this finding, as borne out by these 10-year results, which shows that radiotherapy has a significant impact on reducing loco-regional recurrence in patients at high risk after mastectomy. There is an apparent survival benefit although, because of the small numbers in this trial, this has not reached statistical significance.

Adult↗
PubMed2002

Neuroendocrine differentiation and prognosis in breast adenocarcinoma.

AIMS: Neuroendocrine differentiation has been detected, and its prognostic value studied, in a number of common human carcinomas. To date there are few detailed studies examining its relevance in breast carcinoma. In this study we evaluate the frequency and prognostic importance of neuroendocrine differentiation in breast adenocarcinoma. METHODS AND RESULTS: The presence of neuroendocrine differentiation, defined as positive reactivity for three markers, neuron-specific enolase (NSE), chromogranin A and/or synaptophysin, has been evaluated in 99 patients with primary operable breast cancer using standard immunocytochemical techniques. A consecutive cohort of patients were selected from the Nottingham/Tenovus series. Comprehensive patient and tumour records have been maintained, and patients were followed up according to a defined protocol. Eighteen cases were positive for NSE, 10 for chromogranin A and 13 for synaptophysin. Eleven percent were positive with more than one neuroendocrine marker. No significant association was found between neuroendocrine differentiation and tumour size, grade, stage or the prevalence of vascular invasion. There was no significant difference in either overall or disease-free survival between patients with or without neuroendocrine differentiation. CONCLUSIONS: In this study we confirm that neuroendocrine differentiation can be identified in a subset (10-18%) of human breast carcinomas. This phenomenon appears to have no relationship to established prognostic factors or patient outcome.

Adenocarcinoma↗
PubMed2001

E-cadherin as a prognostic indicator in primary breast cancer.

Epithelial cadherin (E-CD) is a member of the cadherin family of cell adhesion molecules and has been implicated as an invasion suppressor molecule in vitro and in vivo. We analysed 174 breast tumours from the Nottingham/Tenovus Breast Cancer Series immunohistochemically for E-CD expression using the mouse monoclonal antibody HECD-1 (Zymed Laboratories Inc.). In normal epithelial cells E-CD was strongly expressed at cell-cell boundaries. 66% of the breast cancers examined had reduced intensity of E-CD expression with 74% having significant reductions in the proportion of E-CD-positive tumour cells. Using a combined intensity/proportion score, significant associations were found between E-CD expression and tumour type (P </= 0.001). ER status (P = 0.026) and histological grade (P = 0.031). Expression of E-CD was not found to be related to recurrence, distant metastases, lymph node stage, vascular invasion, primary tumour size, prognostic group or survival. Thus E-CD expression in human breast cancer appears to have minimal prognostic value, but may have a role as a phenotypic marker.

Adult↗