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Biomedical subjects

R D Macmillan

Publications and source records attributed to R D Macmillan.

33 records · Page 2Linked to original sources
PubMed2003

Radioisotope for occult lesion localisation (ROLL) of the breast does not require extra radiation protection procedures.

AIM OF STUDY: Dosimetry data from patients and hospital personnel involved in the use of radioisotope for occult lesion localisation (ROLL) of the breast were collected to determine the need for extra radiation protection procedures. METHODS: Sixty-three patients have been enrolled to date into a randomised trial evaluating ROLL. Two megabecquerels of (99m)Tc- MAA in a syringe was mixed with X-ray contrast medium; this was injected directly into the lesion under image guidance. A gamma-detecting probe (Neo-Probe) was used to locate the area of radioactivity. Radiation doses to all staff groups were estimated using time and motion studies and dose rate measurements at a range of distances during each stage of ROLL. RESULTS: The finger dose [FD](+/-95% CI) was considered to be the critical variable for surgeons and radiologists. Surgeon FD=9.3+/-3.3 microSv, Radiologist FD=0.5+/-0.13 microSv. Whole body doses [WBD](+/-95% CI) were estimated for other staff groups. Nurse WBD=0.4+/-0.4 microSv, porter WBD: nil, contamination and waste: nil. CONCLUSIONS: In the case of a surgeon performing 100 procedures per annum, a FD dose of approximately 1 mSv is received, well within the annual dose limit of 150 mSv. Annual WBD to assisting staff may reach 0.04 mSv, compared to an annual limit of 6 mSv. These low doses and the lack of contamination of radioactive waste indicate that no additional radiation protection measures are required.

Breast Neoplasms↗
PubMed2003

Excision biopsy findings of patients with breast needle core biopsies reported as suspicious of malignancy (B4) or lesion of uncertain malignant potential (B3).

AIMS: The UK National Health Service Breast Screening Programme has proposed five categories for reporting breast needle core biopsies. The majority of cores are reported as benign (B1), normal (B2) or malignant (B5). The predictive value of the two borderline categories suspicious of malignancy (B4) and lesion of uncertain malignant potential (B3) was studied. METHODS AND RESULTS: Over a 2-year period a total of 3822 breast needle core biopsies were performed, with 2997 from symptomatic patients and 825 from women undergoing mammographic screening, including 43 B4 reports (40 patients) and 120 B3 reports (116 lesions in 115 patients). The frequencies of B4 (2.5% versus 0.7%) and B3 cores (7.3% versus 2.0%) were both higher in screening than in symptomatic patients. B4 was most commonly used for small fragments of atypical cells separate from the main core or focal atypical intraductal proliferations. The criteria for calling a core B3 were: atypical intraductal epithelial proliferations (including foci that in excision specimens would be classified as atypical ductal hyperplasia), lobular neoplasia, radial scar, papillary lesion, fibroepithelial lesion with cellular stroma and spindle cell proliferations. Excision biopsies were performed in 39 patients with B4 core and 96 with B3 core. Invasive carcinoma or ductal carcinoma in situ was seen in 33 of the patients with B4 (85%) and in 29 of those with B3 cores (25%). Some categories of B3 core were associated with a higher rate of malignancy (40% for atypical intraductal epithelial proliferations and 46% for lobular neoplasia). CONCLUSIONS: The positive predictive value for carcinoma is high following a B4 core (86%). The lesion should be excised, but definitive cancer treatment is not appropriate. In some cases a definite diagnosis of malignancy can be made on repeat core. The B3 group is more heterogeneous and has a lower rate of malignancy on further biopsy (25%). The majority of B3 lesions require excision. All these patients should be discussed at multidisciplinary meetings.

Biopsy, Needle↗
PubMed2003

Is the presence of mammographic comedo calcification really a prognostic factor for small screen-detected invasive breast cancers?

AIM: It has been suggested that the use of traditional prognostic factors such as histological grade and lymph node stage are not reliable predictors of outcome for small (<15 mm diameter) screen-detected breast cancers. It has also been suggested that the presence of mammographic comedo (casting) microcalcifications may be an important prognostic factor. We have determined prognostic factors for small screen-detected cancers in a univariate and multivariate fashion. MATERIALS AND METHODS: Histological grade, lymph node stage, invasive tumour size and vascular invasion status was obtained on 161 consecutive patients with primary invasive breast cancer <15 mm diameter, detected by screening. The Nottingham Prognostic Index was calculated for each patient. The mammograms were assessed for the presence of microcalcifications, these being classified as either comedo or non-comedo. Survival data was also obtained. RESULTS: Overall survival in this group of patients was excellent with only 12 patients (7.5%) dying from their breast cancer (mean follow-up 7.5 years). Univariate analysis showed a significant association between lymph stage and outcome (chi(2)=9.68, P=0.008). No significant association was demonstrated between the presence of comedo calcification and survival. Multivariate analysis confirmed lymph node stage as the only independent prognostic factor for these small screen-detected breast cancers (chi(2)=7.18, P=0.007). There were significant associations between the presence of comedo calcification on the screening mammogram and high histological grade and small tumour size. CONCLUSION: Although the overall outcome for small screen-detected breast cancers (<15 mm diameter) is excellent, the presence of lymph node metastases is associated with a significant reduction in long-term survival. The presence of mammographic comedo calcification is not an independent prognostic factor, but is closely related to histological grade.

Breast Neoplasms↗
PubMed2001

Sentinel node biopsy for breast cancer may have little to offer four-node-samplers. results of a prospective comparison study.

The aims of the study were to determine how often four node axillary sampling (4NAS) encompasses the sentinel node (SN) and to compare the relative sensitivity of 4NAS with sentinel node biopsy (SNB) for axillary node staging. 200 patients with breast cancer were preoperatively injected with 27 MBq 99m-Tc-labelled colloid adjacent to the tumour. At operation, standard 4NAS was performed. Each node was counted ex vivo using a probe. A search was then made to find a node with higher counts in vivo directed by the probe. If found, it was excised. Each node was submitted separately to pathology. A SN was identified in 191 patients (96%). The SN was contained in the 4NAS in 153 patients (80%) and identified separately in 38 patients (20%). Of 60 node-positive patients, 49 were positive by 4NAS and SNB, the SN was not identified in 2 and in 8 the SN was falsely negative compared with 4NAS. For 1 patient, the SN was positive and the 4NAS negative. SNB performed using radiolabelled colloid has no advantage over 4NAS when nodes are assessed by standard histological technique.

Axilla↗
PubMed2001

Germ line mutations associated with breast cancer susceptibility.

Laboratory-based research in germ line mutations associated with breast cancer susceptibility is rapidly being integrated into clinical practice with profound implications. A Medline search was performed for all relevant articles published since 1990. Where appropriate, historical articles referenced in those identified were also reviewed. The results suggested that while mutations in the BRCA1 and BRCA2 genes are the most clinically relevant, much of the data on which clinical decisions are based must be interpreted with wide confidence intervals. Between 1 in 152 and 1 in 833 individuals carry such mutations. They account for less than 5% of all breast cancer, but up to 10% of cancers in those under the age of 40 years. Founder mutations are responsible for a larger proportion of breast cancer cases within certain inbred communities. Phenotypic expression and penetrance of different mutations is not currently predictable and estimates of penetrance are largely based on highly selected populations. BRCA1 mutations are more commonly associated with ovarian cancer than BRCA2 mutations. BRCA1 cancers tend to have more distinct pathological features and are usually oestrogen receptor (ER)-negative. To conclude, the evidence in this review suggests that caution should be exercised when translating scientific progress in breast cancer germ line genetics into clinical practice. Most of the available data are derived from studies on highly selected populations. The importance of other less penetrant, but more prevalent, germ line mutations may be realised in the future.

Age Factors↗
PubMed2000

Screening women with a family history of breast cancer--results from the British Familial Breast Cancer Group.

AIMS: To determine the efficacy of screening women under age 50 with a significant family history of breast cancer. METHODS: Results from 22 Breast Units in the UK identified as being able to provide data were surveyed and pooled through regional data managers or consultant breast specialists. RESULTS: Data relating to 8783 women screened and 9075 woman years of follow-up was analysed. Cancer incidence was 11.3/1000/year. The rate of cancer detection was 4. 78/1000 at prevalent screening and 4.52/1000 at incident screening. Median age at diagnosis was 43 years. Interval cancers presented at a rate of 2.45/1000. Comparison with the National Health Service Breast Screening Programme for women aged 50-64 revealed a similar rate of cancer detection and a similar incidence of ductal carcinoma in situ. The pathological features of screen-detected cancers in this study strongly suggest that prognosis for these women is more favourable than if they had presented symptomatically. CONCLUSIONS: This study provides evidence to suggest that screening young women with a significant family history of breast cancer is effective and that a survival benefit can be expected. As a result the British Familial Breast Cancer Group proposes a co-ordinated prospective observational study.

Adult↗
PubMed2000

Effect of evening primrose oil on clinically diagnosed fibroadenomas.

The effects of oil of evening primrose oil on fibroadenomas was assessed over a 6-month period. Eleven out of 21 (52%) of fibroadenomas receiving evening primrose oil and 8 out of 19 (42%) controls reduced in size. This study demonstrates that evening primrose oil does not significantly effect the natural history of breast fibroadenomas.

Journal Article↗
PubMed2000

INK4a gene expression and methylation in primary breast cancer: overexpression of p16INK4a messenger RNA is a marker of poor prognosis.

Frequent deletions or mutations of the INK4 gene, which encodes the cyclin-dependent kinase 4 inhibitor p16INK4a, have been documented in various human cancers, but little is known about the role of this tumor suppressor gene in primary breast cancer. We examined p16INK4a mRNA expression and its relationship with cyclin D1 and estrogen receptor (ER) expression in 314 primary breast cancers using Northern blots probed with a p16 exon 1alpha-specific cDNA. Tumor samples overexpressing p16INK4a were predominantly ER negative with low levels of cyclin D1. Cyclin D1 and ER mRNA levels in the high p16INK4a expressers were significantly lower than those in the remainder of the population (P = 0.0001). Furthermore, the mean p16INK4a mRNA level in the ER-negative tumors was significantly higher than that in the ER-positive group (P = 0.0001). Because the INK4 gene is frequently inactivated by de novo methylation, we investigated the frequency of INK4a exon 1alpha methylation in a subset of 120 primary breast cancers using methylation-specific PCR; 24 of these were methylated. These findings indicate that high expression of p16INK4a and reduced expression due to de novo INK4a methylation are frequent events in primary breast cancer. In a subset of 217 patients for whom detailed clinical data were available, high p16INK4a mRNA expression was associated with high tumor grade (P = 0.006), > or = 4 axillary lymph node involvement (P = 0.004), ER negativity (P = 0.0001), and increased risk of relapse (P = 0.006). The significant negative correlation between p16INK4a and ER gene expression raises issues regarding their functional interrelationships and whether high p16INK4a expression may be associated with a lack of hormone responsiveness in breast cancer.

Breast Neoplasms↗
PubMed1999

Margin assessment by cavity shaving after breast-conserving surgery: analysis and follow-up of 543 patients.

AIMS: To analyse cavity shaving as a method of assessing completeness of surgical excision after breast-conserving surgery. METHODS: Shavings were taken from the wall of the cavity remaining in the breast after breast-conserving surgery in 543 women. Each shaving was extensively sectioned and the presence and type of microscopic disease recorded. Disease in cavity shavings (tumour bed positivity) was correlated with clinicopathological factors as well as overall survival. RESULTS: Tumour bed positivity (TBP) was found in 37% of patients (16% with invasive disease). Patients were selected for further surgery according to the extent of positivity, which varied widely. A total of 15% of patients underwent re-excision or mastectomy. TBP was significantly associated with high tumour grade, presence of an extensive intraduct component, young age and large tumour diameter. It was also associated with a significantly shorter overall survival when compared to patients who were tumour bed negative. CONCLUSIONS: Cavity shaving is a practical and sensitive method of assessing completeness of excision after breast-conserving surgery. In addition it may provide useful prognostic information.

Adult↗
PubMed1998

EMS1 gene expression in primary breast cancer: relationship to cyclin D1 and oestrogen receptor expression and patient survival.

The EMS1 and CCND1 genes at chromosome 11q13 are amplified in about 15% of primary breast cancers but appear to confer different phenotypes in ER positive and ER negative tumours. Since there are no published data on EMS1 expression in large series of breast cancers we examined the relationship of EMS1 expression with EMS1 gene copy number and expression of mRNAs for cyclin D1 and ER. In a subset of 129 patients, where matched tumour RNA and DNA was available, EMS1 mRNA overexpression was associated predominantly with gene amplification (P = 0.0061), whereas cyclin D1 mRNA overexpression was not (P = 0.3142). In a more extensive series of 351 breast cancers, there was no correlation between cyclin D1 and EMS1 expression in the EMS1 and cyclin D1 overexpressors (P = 0.3503). Although an association between EMS1 mRNA expression and ER positivity was evident (P = 0.0232), when the samples were divided into quartiles of EMS1 or cyclin D1 mRNA expression, the increase in the proportion of ER positive tumours in the ascending EMS1 mRNA quartiles was not statistically significant (P = 0.0951). In marked contrast there was a significant stepwise increase in ER positivity in ascending quartiles of cyclin D1 mRNA (P = 0.030). A potential explanation for this difference was provided by the observation that in ER positive breast cancer cells oestradiol treatment resulted in increased cyclin D1 gene expression but was without effect on EMS1. The relationship between EMS1 expression and clinical outcome was examined in a subset of 234 patients with median follow-up of 74 months. High EMS1 expression was associated with age > 50 years (P = 0.0001), postmenopausal status (P = 0.0008), lymph node negativity (P = 0.019) and an apparent trend for worse prognosis in the ER negative subgroup. These data demonstrate that overexpression of EMS1 mRNA is largely due to EMS1 gene amplification, is independent of cyclin D1 and ER expression and, in contrast to cyclin D1, is not regulated by oestrogen. Independent overexpression of these genes may confer different phenotypes and disease outcomes in breast cancer as has been inferred from recent studies of EMS1 and CCND1 gene amplification.

Adult↗
PubMed1997

Tumour bed positivity predicts outcome after breast-conserving surgery.

BACKGROUND: Local recurrence after breast-conserving surgery is associated with a short distant disease-free survival, particularly if it occurs early. Early recurrence is caused by residual disease left at the time of surgery. Previous studies have demonstrated that disease in the tumour bed is a common finding after breast-conserving surgery. METHODS: The follow-up (mean 4.4 years) of 300 patients who had tumour bed analysis performed by the cavity shaving technique following breast-conserving surgery is presented. Postoperative radiotherapy was administered to all patients. RESULTS: The incidence of tumour bed positivity was 39.3 per cent. With a selective re-excision policy the local recurrence rate was 2.0 per cent and distant recurrence rate 10.4 per cent. Multivariate analysis identified lymphovascular invasion, oestrogen receptor status and tumour bed status as independent predictors of time to distant recurrence. CONCLUSION: A low rate of local recurrence can be achieved using this technique of margin assessment. Tumour bed status may be a useful prognostic factor following breast-conserving surgery.

Adult↗
PubMed1996

Local recurrence after breast-conserving surgery for breast cancer.

Local recurrence following breast-conserving surgery for breast cancer is a significant failure of local treatment. This article reviews the mechanisms, risk factors and overall significance of such local recurrence. The presence of disease at excision margins, an extensive intraduct component, lymphatic vessel invasion, tumour grade and tumour size are currently the best predictors of risk for local recurrence. Early local recurrence is due to residual disease and is associated with both decreased distant disease-free survival and overall survival; it appears to reflect aggressive biological characteristics of the primary tumour. The importance of adequate local treatment for breast cancer is discussed.

Breast Neoplasms↗
PubMed1994

Breast-conserving surgery and tumour bed positivity in patients with breast cancer.

Between March 1988 and April 1992, in 264 patients undergoing breast-conserving surgery for stage I and II cancer, the tumour bed was analysed for residual disease. After a conventional breast-conserving operation the entire wall of the cavity from which the lumpectomy specimen had been taken was excised. This was involved with disease in 38 per cent of patients. Additional random biopsies of the secondary cavity were performed in 130 patients and were involved with disease in 13 per cent. Residual disease was detected in the tumour bed of 37 per cent of patients with screen-detected tumours.

Adult↗