Biomedical subjects
Publications and source records attributed to K Mokbel.
We report a case of a full thickness burn to the breast following the application of a hot-water bottle to the insensate skin overlying a mammary prosthesis.
Phyllodes tumour (PT) is a rare neoplasm of the female breast that resembles fibroadenoma but occurs in an older age group. We retrospectively reviewed the medical records of 30 women who were treated for phyllodes tumour in our centre. Histological examination was performed by an experienced breast pathologist in all cases and tumours were classified as benign, border line malignant or malignant according to standard histological criteria. The mean age at diagnosis was 49 years (range: 19-80 years). Twenty-one (70%) of 30 tumours were benign and 9 (30%) were malignant (n=7) or borderline malignant (n=2). The mean tumour size was 46 mm (range: 20-100 mm). The final microscopic margins contained tumour in 13 (43%) of 30 cases and were free of tumour in 17 (57%) of 30 patients. After a median follow-up period of 6 years (range: 6 months-20 years), the tumour recurred locally in 5 (17%) patients. One patient had six local recurrences over an 18-year period. Local recurrences were more frequently observed in patients with malignant tumours compared with those with benign lesions (33% versus 10%). However, this association failed to reach statistical significance. There was no association between local recurrence, patient age, tumour size or positive microscopic margins. There was one death (3%) associated with a completely excised malignant tumour. The present study suggests that histological type and margins do not accurately predict the clinical course of PT and that there is a need to identify novel biological markers that more accurately predict the behaviour of this rare neoplasm.
We retrospectively reviewed the microscopic findings in 32 histologically confirmed radial scars in 31 women diagnosed in our unit during 1994-1998. The median age at diagnosis was 53 years (range 47-63 years). Thirty-one (97%) of 32 lesions presented as screen detected mammographic abnormalities (28 stellate lesions, 2 microcalcifications and only 1 architectural distortion). One lesion presented as a palpable breast mass. Stereotactic or ultrasound-guided fine needle aspiration cytology (FNAC) was performed in 28 cases. Cytological analysis of FNAs revealed malignant cells (C5) in 8 (29%) cases, highly suspicious cells (C4) in 3 (11%) cases, atypical benign cells (C3) in 7 (25%) cases and benign epithelial cells (C2) in 10 (35%) cases. All non-palpable lesions were surgically excised following wire localization. Histological examination of the breast specimens (mean weight=16 g) demonstrated, in addition to a radial scar, 6 invasive carcinomas (2 infiltrating ductal, 2 tubular, 1 mixed ductal/lobular and 1 secretory carcinoma) and 4 ductal carcinoma in situ lesions (2 high grade, 1 high grade with micro-invasion and 1 low grade) arising in the radial scar. Of the remaining cases the radial scar was associated with atypical epithelial hyperplasia in 2 cases and regular epithelial hyperplasia in 17 cases (4 florid and 13 mild to moderate). In the 10 cases associated with malignancy, 9 had FNAC and was reported as malignant (C5) in 6 (67%) cases, highly suspicious (C4) in 2 (22%) cases and atypical (C3) in 1 (11%). False positive FNAC (C5) occurred in two patients, one of whom presented with pleomorphic microcalcifications suggestive of ductal carcinoma in situ. This patient was treated with a wire guided segmental mastectomy. All invasive tumours were less than 20 mm in size (T1) and of these 4 were grade I and 2 were grade II. Axillary dissection was performed in 4 patients none of whom had axillary node metastases. Our study demonstrates a significant incidence of malignancy associated with radial scars (31%) suggesting that radial scars may be premalignant lesions. This is supported by detecting various stages of mammary carcinogenesis (atypical epithelial hyperplasia, ductal carcinoma in situ, and early invasive malignancy) in these lesions. Fine needle aspiration cytology seems to be unreliable in the diagnosis of radial scar associated malignancy (67% sensitivity and 91% specificity). Stellate lesions, therefore, should be excised to obtain an histological diagnosis regardless of cytological findings. Further studies examining the biology of radial scars are required.
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Cytokines such as interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF alpha), have been identified as important regulators of aromatase activity in fibroblasts derived from normal and malignant breast tissues, and may play an important role in controlling aromatase activity in breast tumours. The major source of such cytokines within breast tumours remains to be established but macrophages and lymphocytes, which can infiltrate tumours, have been identified as a potential source of aromatase stimulatory cytokines. To obtain further insight into the possible role played by the immune system in cancer development, and in particular its ability to regulate aromatase activity via cytokine production, we have obtained peripheral blood monocytes and lymphocytes from an immunosuppressed kidney transplant recipient, receiving cyclosporin A therapy, and a woman with breast cancer. Monocytes and lymphocytes were stimulated with lipopolysaccharide (LPS), and the conditioned medium (CM) collected from these cells was tested for its ability to stimulate aromatase activity in fibroblasts derived from normal breast tissue from a woman undergoing lumpectomy for the removal of a breast tumour. The white blood cell count was lower for the immunosuppressed patient, mainly because of the reduction in the number of monocytes and lymphocytes. The ability of CM from the monocytes and lymphocytes of the immunosuppressed patient to stimulate aromatase activity was significantly reduced (68% and 82% for monocytes and lymphocytes, respectively) compared with that of CM from the cells of the woman with breast cancer. It is possible, therefore, that immunosuppression, which has been found to be associated with a reduction in the incidence of de novo breast cancer in kidney transplant recipients, may exert its effect by inhibiting cytokine production by the cells of the immune system and thus oestrogen synthesis. In contrast to the stimulatory effects that TNF alpha has on aromatase activity in breast fibroblasts, in MCF-7 breast cancer cells, which possess low aromatase activity, it reduced activity. However, the extent of inhibition of aromatase activity in these epithelial cells was much lower than the marked stimulation which it can induce in breast fibroblasts.
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We retrospectively reviewed the records of 317 needle-localization (NL) biopsies performed at the Royal Marsden Hospital during 1989-1992. The malignancy yield in our centre, where there is an emphasis on cooperation with an experienced radiologist and breast pathologist, was 48% (151/317), with benign to malignant biopsy ratio of 1:1:1. Analysis of the histopathological findings of the malignant lesions revealed a 45% (68/51) incidence of positive microscopic margins. Of these 68 patients, 50 had re-excisions, including nine patients who required mastectomy. Twenty-eight of the re-excisions (56%) contained residual tumour, of which five (18%) were invasive carcinoma > 3 mm (size range 1-19 mm) and 13 (46%) were residual DCIS > 1 mm (size range 1-40 mm). Our findings suggest a significant incidence of residual disease associated with positive microscopic margins in NL-detected nonpalpable cancers. Therefore, our current practice of performing a wider re-excision for positive margins is justified. Stereotactic fine-needle aspiration cytology was not performed by the radiologist referring these cases, but it should be performed preoperatively and if the test is positive, definitive treatment in the form of wide local excision or quadrantectomy is carried out in the first instance in order to avoid a second-surgical procedure.
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BACKGROUND: The sentinel node biopsy (SNB) is a reliable and minimally invasive procedure, representing a new standard of care for patients with clinically node-negative breast cancer. Several studies have confirmed the reliability and the accuracy of this new procedure. Accurate intraoperative evaluation of sentinel lymph nodes (SLNs) can determine the need for immediate axillary node clearance thus reducing arm morbidity in SLN-negative patients and avoiding a second surgical procedure in patients with positive SLNs. The aim of this study is to determine the accuracy and the limitations of intraoperative frozen section (IFS) analysis of SLNs during breast cancer surgery. PATIENTS AND METHODS: 96 female patients with clinically node-negative T1-T2 breast cancer who underwent the SNB procedure and IFS analysis by single section standard staining in two hospitals were reviewed. The SNB procedure was performed using the patent blue dye method alone or the combination of the dye and radioactive isotope techniques. The results of IFS and the final histology were compared. RESULTS: The mean number of SLNs removed was 2. Overall, 22% (21/96) of patients were found to be SNB-positive on final histology. Based on patients, there was a 96.8% concordance between the results of the IFS and the final histology; the sensitivity was 86% (18/21), and the specificity was 100%. There were 3 cases of false negative all of which contained micrometastases only. When micrometastases were excluded, the sensitivity was 100%. Based on SLNs (n = 196), the sensitivity was 91%, and the specificity was 100%. CONCLUSION: Intraoperative frozen section of sentinel lymph nodes in patients with early breast cancer is highly accurate for macrometastases but not for micrometastases.
The main controversies surrounding the management of DCIS evolve around the need for adjuvant radiotherapy (RT) after adequate local excision (LE) of localized lesions and the role of adjuvant endocrine therapy. Three recent randomized controlled trials (RCTs) have demonstrated that adjuvant RT significantly reduces the incidence of ipsilateral breast tumor recurrence (IBTR) after "adequate" LE. The role of adjuvant tamoxifen in the treatment of DCIS was evaluated in two RCTs: one demonstrated a significant reduction in IBTR with tamoxifen and the other did not. Retrospective subgroup analysis of the former demonstrated that the reduction in all breast cancer events was even greater for ER positive tumors, but no benefit was observed for ER negative lesions. The effect of tamoxifen was greater in both trials for women under 50 years.
UNLABELLED: The Wnt family encodes secreted signaling molecules involved in cell adhesion and, by implication, cell growth. Wnt5a has been shown to behave as a putative oncogene and also as a tumour suppressor gene. This is a reflection of its role within a multi-step pathway and in the variety of ways in which its production can be stimulated or switched off. Wnt genes can be functionally separated into two classes; those that activate the canonical Wnt/beta-catenin pathway and those that activate the Wnt/Ca++ pathway. Wnt5a signals through frizzled receptors and, depending upon which frizzled receptor is present, may activate either pathway. Therefore the observed function of Wnt5a is entirely dependent upon its context, hence the confusion over its role in tumorigenesis. This study examines Wnt5a mRNA expression using RT-PCR in human breast cancer. MATERIALS AND METHODS: One hundred and twenty malignant breast tumours and 33 normal breast tissues were analysed. The levels of transcription of Wnt5a were determined using real-time quantitative PCR. Levels of expression were analysed against staging, nodal involvement, grade, distant metastasis and survival over a 6-year follow-up period. RESULTS: Levels of Wnt5a mRNA were lower in tumours than in normal tissue (mean values: 107 vs. 62.7). They fell further with increasing stage using the Nottingham Prognostic Index. This became statistically significant when NPI3 was compared to normal tissue (p=0.043, t-test). There was a trend towards lower levels of Wnt5a in those with progressive disease, however, this did not reach statistical significance. In patients with ER-negative disease, lower levels of Wnt5a were significantly associated with a worse clinical outcome (p=0.016). CONCLUSION: There is a trend for mRNA levels to be lower in cancerous tissue and lower still in those showing more aggressive behaviour. This is consistent with the hypothesis that Wnt5a is a tumour suppressor gene with potential clinical applications.
UNLABELLED: Previous studies investigating the insulin-like growth factor 1 receptor (IGF-1R) expression in breast cancer tissue and adjacent non-neoplastic breast tissue (ANCT) have produced conflicting results. The IGF-1 and IGF-1R expression in pairs of breast cancer tissue and ANCT were investigated using RT-PCR and immunohistochemistry. The results of both methods were compared. MATERIALS AND METHODS: IGF-1 and IGF-1R mRNA from 31 specimen pairs were estimated using RT-PCR. Immunohistochemistry for IGF-1R was carried out on 20 specimen pairs and the strength of staining was scored. RESULTS: The mean relative IGF-1 mRNA level was lower in the cancerous tissue (mean 0.450 +/- 0.206) than in the ANCT (mean 0.632 +/- 0.384) (paired t-test, p = 0.001). There was no measurable difference in relative IGF-1R mRNA levels in the cancerous tissue (mean 0.146 +/- 0.08) and the ANCT (mean 0.14608 +/- 0.108) (paired t-test, p = 0.807). Using immunohistochemistry, there was no statistical difference (paired t-test, p = 0.910) in IGF-1R staining scores between cancer (mean 1.93) and ANCT (mean 1.90). The comparison between the two methodologies showed no correlation (Pearson's Correlation Coefficient = -0.393). DISCUSSION: It can be concluded that IGF-1 expression is lower in cancerous tissue, thus supporting a paracrine relationship between cancerous tissue and ANCT, which may be useful in the prevention, diagnosis and treatment of breast cancer. There was no difference in the expression of the IGF-1 receptor in both types of tissue, as proven by RT-PCR and immunohistochemistty. Conflicting results in previous studies may be due to the different methods used to measure IGF-1R expression.
BACKGROUND: Dietary elements and, in particular, dairy products have been implicated in the etiology of breast cancer. High saturated fat contents, contaminants such as pesticides, and insulin-like growth factor I (IGF-1) have been hypothesized as possible carcinogenic factors. In contrast, calcium, vitamin D, and conjugated linoleic acid (CLA) all are considered to reduce breast cancer risk. We aim to review the current epidemiological literature on the relationship between the intake of dairy products and breast cancer risk. METHODS: A Medline search was conducted using the key words breast neoplasms and dairy products. Further articles were obtained by cross-matching references of relevant articles. Thirty-nine case-control and 11 cohort studies were identified since 1981. Two meta-analyses and several review articles were also noted. RESULTS: Results from previous studies were analyzed and comparisons were made between each type of study. Controversy exists regarding this subject and we found conflicting evidence in recent literature regarding this hypothesis. CONCLUSION: There is no substantial epidemiological evidence to support a significant link between the intake of dairy products and breast cancer risk.
BACKGROUND: Over the last decade, interest in the physiological role of bioactive compounds in plants has increased dramatically. Of particular interest in relation to human health are the class of compounds known as the phytoestrogens, which embody several groups of nonsteroidal estrogens that are widely distributed within the plant kingdom, including isoflavones and lignans. Epidemiological studies suggest that diets rich in phytoestrogens, particularly soy and unrefined grain products, may be associated with low risk of breast cancer. This review presents the studies published so far exploring a link between dietary phytoestrogens and breast cancer risk. METHODS: A Medline search was conducted using the key words below. Further articles were obtained by cross-matching references of relevant articles. Twenty-one case-control and 15 prospective studies were identified since 1978. One meta-analysis and several review articles also were noted. RESULTS: Results from previous studies were analyzed and comparisons were made between each type of study. Controversy exists regarding this subject, and we found conflicting evidence in recent literature regarding this hypothesis. CONCLUSION: There is no clear evidence that phytoestrogen intake influences the risk of developing breast cancer.