CHRISTOS MARKOPOULOS is Associate Professor of Surgery, Athens University Medical School and Director of the Breast Unit at ‘Laiko’ University Hospital of Athens, and Athens Medical Centre, Greece. He qualified from Athens University Medical School in 1979 and he specialized in general surgery (1985). He received his MD from Athens University - Greece in 1985 and his MPhil degree in Oncology-Breast Cancer from University of London –UK in 1988. He specialized in Breast Cancer Management working as senior registrar in surgery at the Breast Unit of St. George’s Hospital and Medical School and at The Royal Marsden Hospital in London-UK (1985-8). He has also been research fellow at Lundwing Institute for Cancer research at Sutton-UK. Prof Markopoulos has published over 250 scientific papers in international and Greek medical journals and has also authored several books on breast disease. He is a member of several medical associations and societies including BASO, ACBS, EUSOMA, ESSO, and since 2000, he chairs ‘The Hellenic Society of Breast Surgeons’ and he is responsible of the ‘education and training’ and ‘clinical trials’ section of the society. He is the responsible professor of the elective course on ‘Breast Disease’ for the final year students of Athens University Medical School. He is national coordinator for various international trials and president or member of the scientific committees of Greek, Breast Cancer Advocacy Groups and Europa Donna Hellas. Dr Markopoulos has organized a large number of national and international postgraduate courses and meetings on ‘Breast Cancer’ over the last 15 years and he has lectured extensively as invited speaker at national and international congresses.
Abstract: Patient satisfaction with cosmetic outcome and the psychological impact of breast cancer surgery were evaluated. A total of 207 patients with primary breast cancer, treated with either breast-conserving surgery (n = 83), modified radical mastectomy without reconstruction (n = 108), or mastectomy with delayed breast reconstruction (n = 16) rated their cosmetic outcome and satisfaction following surgery, and the impact of surgery on their self-esteem and sexual life, by questionnaire. Patients undergoing breast-conserving surgery were most satisfied with their surgery and body image, followed by those treated with mastectomy with delayed reconstruction. Although diagnosis of breast cancer had a negative impact on the psychology of all patients, those undergoing breast-conserving surgery or mastectomy with delayed reconstruction were more satisfied and reported a lower impact on their self-esteem and sexual life versus those who only had mastectomy. Diagnosis of breast cancer has a negative psychological impact on the patient, but the type of surgery has a significant role in post-operative self-esteem and sexual life.
Abstract: INTRODUCTION: Extended adjuvant endocrine therapy for breast cancer with aromatase inhibitors may potentially alter the lipid profile of postmenopausal patients and thus increase the risk of developing cardiovascular disease. In this study, a subprotocol of the ATENA (Adjuvant post-Tamoxifen Exemestane versus Nothing Applied) trial, we compared the effect of the steroidal aromatase inactivator exemestane on the lipid profile of postmenopausal patients with operable breast cancer, in the adjuvant setting, with that of observation alone after completion of 5 to 7 years of primary treatment with tamoxifen. METHODS: In this open-label, randomized, parallel-group study, 411 postmenopausal patients with operable breast cancer, who had been treated with tamoxifen for 5 to 7 years, were randomized to either 5 additional years of exemestane (25 mg/day; n = 211) or observation only (n = 200). Assessments of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total serum triglycerides (TRG) were performed at baseline and then during each follow-up visit, performed at either 6 or 12 months, according to the center's clinical practice, until completing 24 months in the study. RESULTS: TC and LDL levels increased significantly across time for both arms; TC increase was more pronounced for the observation arm, and that was sustained up to 24 months. HDL levels decreased significantly across time for the exemestane arm, whereas no significant change was detected across time for the observation arm. Triglyceride levels decreased significantly across time on both arms, with no difference detected in changes from baseline between the exemestane and the observation arms. CONCLUSIONS : Exemestane lacks the beneficial effect of tamoxifen on lipids; however, sequential adjuvant treatment with exemestane in postmenopausal breast cancer patients after cessation of 5 to 7 years of tamoxifen does not appear to alter the lipid profile significantly compared with that of an observational arm. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00810706.
Abstract: There is no standard treatment for breast cancer patients whose tumors have been exposed both to anthracyclines and taxanes. Oxaliplatin shows synergism with 5-fluorouracil (5-FU) and capecitabine is an oral prodrug of 5-FU with known efficacy in pretreated patients. This phase II trial studied the efficacy and toxicity of the oxaliplatin-capecitabine combination as salvage treatment in breast cancer patients pretreated with anthracyclines and taxanes. Patients received oxaliplatin 80 mg/m(2) on day 1 followed by oral capecitabine 1800 mg/m(2) divided in two doses for 7 days every two weeks for a maximum of twelve courses or until disease progression. Twenty-eight patients were evaluable for efficacy and toxicity. Objective responses (all partial) were documented in 9 patients [32%; 95% confidence interval (CI): 13-51.2%]. Responses were documented at all metastatic sites. The median response duration was 5 months (range 3-9), median time to progression was 4.5 months (range 2-10) and median overall survival was 10 months (range 2-18). Myelotoxicity was minimal with grade 3 thrombocytopenia as the main toxicity. Hand-foot syndrome was well tolerated. The present regimen was well tolerated with a rather moderate effectiveness but very significant for this group of patients. Further studies where the combination could be compared with single agent capecitabine are warranted.
Abstract: BACKGROUND: The Greek substudy of the Tamoxifen and Exemestane Adjuvant Multicenter International trial compared the effect of exemestane on the lipid profile of postmenopausal, breast cancer patients to that of tamoxifen in the adjuvant setting. PATIENTS AND METHODS: Lipidemic profile changes were studied in 142 postmenopausal patients randomized to receive either adjuvant exemestane (n=77) or tamoxifen (n=65). Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and serum triglyceride (TRG) levels were measured at baseline and then every 3 months for the first 12 months of treatment and at 18 and 24 months. RESULTS: A trend for a reduction in TC was found in both treatment arms; however, TC and LDL levels were consistently and significantly decreased in tamoxifen arm only. The mean HDL level was higher for the tamoxifen arm compared with the exemestane arm across time. No significant trend was detected throughout the study period on TRG levels on either arm. CONCLUSIONS: Unlike tamoxifen's beneficial effect on TC and LDL levels, exemestane appears to have a neutral effect on lipidemic profile of postmenopausal, breast cancer patients. These data offer additional information with regard to the safety and tolerability of exemestane treatment in the adjuvant setting.
Abstract: 127 Greek breast/ovarian cancer families were screened for germline BRCA1/2 mutations by dHPLC followed by direct sequencing. Our results indicated 16 and 5 breast/ovarian cancer families bearing deleterious mutations in the BRCA1 and BRCA2 genes, respectively. Two novel BRCA2 germline mutations (G4X and 3783del10) are reported here for the first time. Subsequent compilation of our present findings with previously reported mutation data reveals that in a total of 287 Greek breast/ovarian cancer families, 46 and 13 carry a deleterious mutation in BRCA1 and BRCA2, respectively. It should be noted that two BRCA1 mutations, 5382insC and G1738R, both located in exon 20, account for 46% of the families found to carry a mutation. Based on our mutation analysis results, we propose here a hierarchical, cost-effective BRCA1/2 mutation screening protocol for individuals of Greek ethnic origin. The suggested protocol can impact on the clinical management of breast-ovarian cancer families on a national healthcare system level.
Abstract: Neoadjuvant therapy improves patient outcomes substantially by increasing the rate of breast-conserving surgery. Following primary surgery, women with hormone-sensitive early breast cancer remain at risk for loco-regional and systemic recurrence. The most common relapse event, distant metastases, is associated with the poorest outcomes. As a neoadjuvant therapy, anastrozole, letrozole, and exemestane have been investigated in phase 3 studies and have shown efficacy in this setting. All three aromatase inhibitors (AIs) significantly improved the rate of breast-conserving surgery. As initial adjuvant therapy, the third-generation AIs anastrozole and letrozole more effectively reduce recurrence risk compared with tamoxifen following surgery, especially in the first 2 years, when the risk is greatest. Tamoxifen, once the standard initial therapy, is associated with improved disease-free survival but may be more effective at reducing loco-regional recurrence than distant metastases. Initial adjuvant letrozole therapy has also shown a pronounced reduction in the risk of distant metastases early on in the course of therapy. If AIs are not used upfront, sequential use of exemestane or anastrozole following tamoxifen provides greater protection against relapse than continuing on tamoxifen. Side effects associated with estrogen deprivation of AIs are less serious than those of tamoxifen and are easily managed. Various molecular markers are under study as surrogates to predict response to neoadjuvant therapy, which may in turn predict responsiveness to adjuvant therapy. Surgeons treating breast cancer patients and prescribing endocrine therapy should be aware of all treatment strategies, including neoadjuvant and adjuvant hormonal therapy, and inform their patients of the benefits and the potential side effects. Early and long-term-risk reduction with AI treatment should be discussed with patients, as should the management of common AI-associated adverse events.
Abstract: BACKGROUND: Glycogen-rich carcinoma of the breast is a rare histological subtype of breast cancer, usually reported to have poor prognosis. CASE PRESENTATION: We present the case of a 59-year-old woman who underwent a mastectomy for a 3.5 cm clinically palpable left breast carcinoma, originally diagnosed as fibroadenoma on a screening mammogram four years before presentation. Diagnosis of clear cell carcinoma was based on certain histological characteristics of the tumour and immunohistochemical analysis (PAS staining, keratins AE1/AE3, EMA, cytokeratin 7, cytokeratin 20, melanosomes, vimentin, Chromogranin, Synaptophysin, S-100, SMA). No lymph node metastasis was found and as the tumour was ER positive and PgR negative, patient was treated only with an aromatase inhibitor upfront and remains free of disease 48 months now since operation. CONCLUSION: Glycogen-rich clear cell carcinoma of the breast is a rare tumor, its clinical behavior reported to be rather aggressive so far, might varies depending on special characteristics such as low grade and strongly positive ER expression.
Abstract: BACKGROUND: A randomized phase III trial in high-risk breast cancer patients was conducted, to further explore the impact of dose-density in the adjuvant treatment for breast cancer. The safety analysis is presented. PATIENTS AND METHODS: From October 2000 until June 2005, 1121 node-positive patients were randomized to sequential dose-dense epirubicin 110 mg/m(2) and paclitaxel (Taxol, Bristol Myers-Squibb, Princeton, New Jersey, USA) 250 mg/m(2) (group A), or concurrent epirubicin 83 mg/m(2) and paclitaxel 187 mg/m(2) (group B), both followed by three cycles of 'intensified' combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF). Granulocyte colony-stimulating factor was given prophylactically with the dose-dense treatments. RESULTS: Median dose intensity of epirubicin and paclitaxel was double in group A, as designed, with significantly less cycles administered at full dose (P < 0.001). Median cumulative dose of all drugs and total treatment duration, however, were identical between groups. Severe taxane-related toxic effects were more frequent in group A, while severe thrombocytopenia was low and present only in group A. There were no differences in the rates of other hematological toxic effects, including febrile neutropenia. The rates of secondary malignancies were low. CONCLUSION: Both regimens as used in the present study are well tolerated and safe. The rates of severe taxane-related toxic effects and thrombocytopenia, although low overall, are significantly increased with the dose-dense sequential regimen.
Abstract: Vinorelbine and mitoxantrone have both been demonstrated to have significant antitumor activity in patients with breast cancer. The aim of this study was to evaluate the efficacy and safety of the combination as second or third line treatment in patients with metastatic breast cancer (MBC). Fifty-one previously treated patients with MBC were enrolled from October 2001 to May 2004 and 48 were eligible for evaluation. Median age was 59 years (range 33-82) and ECOG performance status was < or =2. Distant sites of metastasis were as follows: liver 64%, bone 49%, lung 36%, lymph nodes 6%, skin 4%, brain 2% and other sites 6%. All patients received vinorelbine 20 mg/m(2), D1+8 and mitoxantrone 10 mg/m(2) D8 every 21 days for 6 cycles. All eligible patients were analyzed for toxicity and response. Two patients (4%) achieved complete response and 12 (25.5%) partial response. The objective overall response rate was 29.5% (95% confidence interval [CI] 17 - 45), 9 (19%) patients had stable disease, 17 (36%) had progressive disease and 7 (15%) were non-evaluable. After a median follow up of 18 months, overall survival was 13 months (range 0.8 - 38+) and median time to disease progression was 5 months (range 1 - 32). A total of 280 cycles was delivered. The relative dose intensities of mitoxantrone and vinorelbine were 79% and 77%, respectively. Toxicities (grade III-IV) were as follows: leukopenia 18 (38%), neutropenia 21 (45%), thrombocytopenia 1 (2%), anemia 4 (8.5%), alopecia 2 (4%) and constipation 1 (2%). Febrile neutropenia was recorded in one patient. There were no treatment related deaths. The combination of mitoxantrone and vinorelbine is an effective regimen with manageable toxicity in pretreated patients with advanced breast cancer.
Abstract: OBJECTIVE: Phantom breast syndrome (PBS) after mastectomy has been hypothesized to represent a complex psychological reaction to mastectomy, but psychological studies concerning PBS are few and inconclusive. This study aimed to assess possible correlations of PBS to current psychopathology and personality dimensions, as well as to examine subjectively experienced provoking and relieving factors for the experience of PBS. METHOD: A total of 105 women who had undergone modified radical mastectomy were interviewed by a structured questionnaire after breast surgery. Moreover, they completed a set of self-administered psychometric scales consisting of Symptom Checklist-90-R, Eysenck personality questionnaire, Zung depression scale, State-Trait Anxiety Inventory and Whiteley Index of hypochondriasis. RESULTS: PBS was experienced by 24 women (22.9%). The majority of them thought that PBS did not interfere with their everyday life. Women with PBS scored significantly higher on the Zung depression scale. Multiple logistic regression analysis revealed that women aged more than 66 years were 82% less likely to have PBS compared to those aged less than 51 years. CONCLUSION: These findings provide evidence that PBS is associated with higher scores of depressive symptomatology and younger age. The nature of such an association remains unclear and calls for further investigation.
Abstract: BACKGROUND: This study aims to explore the debatable role of allergy in breast cancer (BC) by using country-specific biological markers, namely levels of the most prevalent allergen-specific immunoglobulin E in Greece. PATIENTS AND METHODS: Blood samples and clinical information were collected over a 30-month period from 103 women with histologically-confirmed BC and 103 controls from two university hospitals in Athens. Allergen-specific IgE, against the 12 prevailing allergens in Greece were determined; thereafter, a score comprising the sum of the individual values for this battery of serological IgE determinations was created. Bivariate and multiple logistic regression analyses were undertaken using case-control status as the outcome and IgE-scores as the predictor variable, controlling for socio-demographic, gynecological and lifestyle confounders. RESULTS: The serum IgE score seemed to be positively related to BC (OR: approximately 1.73; CI: 0.95-3.14; p-value: 0.07). A positive correlation between serological evidence and allergic history among controls was also found (p-value: 0.06). CONCLUSION: This investigation suggests an IgE-mediated allergic response among women with BC in comparison to their controls. The finding needs confirmation by immuno-epidemiological investigation to clarify the directionality of this association and whether laboratory-ascertained atopy can be considered as a risk-marker of susceptibility in the development of BC.
Abstract: BACKGROUND: Immunotherapy for advanced melanoma induces serologic and clinical manifestations of autoimmunity. We assessed the prognostic significance of autoimmunity in patients with stage IIB, IIC, or III melanoma who were treated with high-dose adjuvant interferon alfa-2b. METHODS: We enrolled 200 patients in a substudy of a larger, ongoing randomized trial. Blood was obtained before the initiation of intravenous interferon therapy, after 1 month of therapy, and at 3, 6, 9, and 12 months. Serum was tested for antithyroid, antinuclear, anti-DNA, and anticardiolipin autoantibodies, and patients were examined for vitiligo. RESULTS: The median duration of follow-up was 45.6 months. Relapse occurred in 115 patients, and 82 patients died. The median relapse-free survival was 28.0 months, and the median overall survival was 58.7 months. Autoantibodies and clinical manifestations of autoimmunity were detected in 52 patients (26 percent). The median relapse-free survival was 16.0 months among patients without autoimmunity (108 of 148 had a relapse) and was not reached among patients with autoimmunity (7 of 52 had a relapse). The median survival was 37.6 months among patients without autoimmunity (80 of 148 died) and was not reached among patients with autoimmunity (2 of 52 died). In univariate and multivariate regression analyses, autoimmunity was an independent prognostic marker for improved relapse-free survival and overall survival (P<0.001). CONCLUSIONS: The appearance of autoantibodies or clinical manifestations of autoimmunity during treatment with interferon alfa-2b is associated with statistically significant improvements in relapse-free survival and overall survival in patients with melanoma.
Abstract: BACKGROUND: There is now increasing evidence that a constitutive expression of cyclooxygenase (COX)-2 plays a role in the development and progression of malignant epithelial tumors. Expression of COX-2 is seen in 93% of melanomas, as determined by immunohistochemistry. Temozolomide (TMZ) has demonstrated activity against melanoma and has been investigated as single agent or in combination. We designed a phase II study to assess the efficacy and toxicity of the combination of TMZ and celecoxib (a COX-2 inhibitor) in patients with advanced melanoma. PATIENTS AND METHODS: From January 2003 to July 2004, 52 patients were enrolled in the study. Nineteen patients were M1a, six M1b and 27 M1c. Patients received TMZ 200 mg/m(2) per day p.o. for 5 consecutive days every 4 weeks and celecoxib 400 mg b.i.d. p.o. for a maximum of six cycles. Celecoxib was continued until progression. RESULTS: The median age was 63 years. There were 29 males and 23 females. Among 50 assessable patients, there were 11 (21.5%) objective responses including five complete responses and six partial responses. Twenty patients (38.5%) had stabilization of their disease, and 19 (36.5%) progressed. The median time to progression was 4.6 months and the median survival 9.5 months. Twenty-two patients (41.5%) completed all cycles of treatment. Median relative dose intensity of TMZ was 0.99 (range 0.6-1.2). Most commonly seen toxic effects included anemia (27.5%), neutropenia (17.5%), thrombocytopenia (33%), nausea/vomiting (75%), gastrointestinal (52%) and fatigue (46.5%). One patient discontinued due to severe toxicity. COX-2 was determined by immunohistochemistry and was expressed in all cases. CONCLUSION: The combination of TMZ and celecoxib is safe and potentially effective in the treatment of metastatic melanoma. Randomized studies are needed to explore the role of celecoxib in combination with chemotherapy or as maintenance treatment in these patients.
Abstract: OBJECTIVE: It was the aim of this study to investigate the effect of tamoxifen withdrawal on markers of lipid metabolism in postmenopausal women with breast cancer who completed tamoxifen therapy and received no further treatment. METHODS: Lipidemic profile changes were studied in 190 postmenopausal patients with operable breast cancer, following cessation of 5-7 years of tamoxifen treatment. Assessments of total cholesterol, high-density lipoprotein, low-density lipoprotein and total serum triglycerides were performed at baseline, 6 months and 12 months. RESULTS: By 6 months, both total cholesterol and low-density lipoprotein levels were significantly increased, and total triglyceride levels were significantly reduced compared with baseline values and maintained to 12 months. There was no significant alteration observed for high-density lipoprotein levels over the study period. CONCLUSION: The beneficial effect of tamoxifen on the lipidemic profile of postmenopausal breast cancer patients seems to be lost in less than 12 months time following cessation of 5-7 years of tamoxifen treatment. A 'rebound effect' on the lipidemic parameters should be expected and those patients should be monitored carefully.
Abstract: PURPOSE: Nipple discharge is reported in 2.5-3% of women with breast carcinoma. Breast carcinoma is found in approximately 8% of surgically treated patients presenting with bloody nipple discharge (ND). METHODS: In the present study 110 women with ND as a presenting symptom were examined. The discharge was spontaneous in 76 and elicited in 11 patients. RESULTS: After surgical intervention benign breast disease was found in 85% of patients. Thirteen women (15%) were found to have malignancy and underwent additional surgery. Cytology of the discharge was positive or suspicious for malignancy in only seven out of 13 patients found to have in situ or invasive carcinoma. CONCLUSION: Women with spontaneous, single duct ND, especially when it is darkish or bloody, should have cytological examination of the fluid and mammography according to their age or additional clinical findings. Most of them will require a microdochectomy, as the possibility of finding a carcinoma among those women is between 10-15%. However, single duct papilloma is the most common cause of bloody discharge.
Abstract: Surgical excision following needle-wire localization of nonpalpable, mammographically detected breast lesions is a very valuable diagnostic and therapeutic procedure. No further treatment is usually required after establishing an accurate histological benign diagnosis of indeterminate lesions on preoperative assessment. On the other hand, ductal carcinoma in-situ (DCIS) and early invasive cancer, properly excised, may sometimes require further management depending on specific histologic findings. An uncommon problem of this procedure is the failure to identify, localize or excise the breast lesion. In this review article, factors that contribute to the failed needle localization procedure are presented.
Abstract: Breast augmentation with the injection of a high-viscosity fluid has been practiced in the past, especially in Asia, resulting in most cases in different varieties of paraffinoma, alternatively known as oleogranulomatous mastitis, a complication of a 'foreign body' reaction type. We report our series of four consecutive cases of destructive paraffinomas that occurred in female patients who had had paraffin injection for cosmetic reasons. Complications due to paraffinoma reactions of breast tissue and skin, as well as progression of the disease and treatment of our patients, are presented here, together with a review of the relevant literature.
Abstract: Gemcitabine and mitoxantrone have both shown significant antitumor activity in patients with breast cancer. The aim of this study was to evaluate the efficacy and safety of this combination as second or third-line treatment in patients with metastatic breast cancer (MBC). Forty-six previously treated patients with MBC were enrolled from June 2000 to November 2002. Mean age was 56 years and ECOG performance status was < or =2. All patients received mitoxantrone 10 mg/m2, D8 and gemcitabine 1000 mg/m2, D1+8 every 21 days for 6 cycles. There were no complete responders. Objective response was observed in 12 patients (26%), 15 (33%) patients had stable disease, 15 (33%) had progressive disease and 4 (9%) were non-evaluable. At median follow-up of 27.8 months, overall survival was 13.3 months (range 0.6-33.8+) and the median time to disease progression (TTP) was 4.4 months (range 0.2-33.8). Toxicities (grade 3-4) were as follows: leukopenia 18 (39%), neutropenia 19 (41%), thrombocytopenia 4 (8.5%), anemia 6 (13%) and alopecia 1 (2%). Febrile neutropenia was recorded in 2 (4%) patients. There were no treatment related deaths. The authors conclude that the combination of mitoxantrone and gemcitabine is an effective regimen in pretreated patients with metastatic breast cancer. Toxicity was manageable.
Abstract: PURPOSE: To assess the prognostic and predictive significance of HER-2 overexpression and high expression of VEGF in high-risk patients with breast cancer treated with dose-dense sequential chemotherapy. PATIENTS AND METHODS: From June 1997 until November 2000, 595 patients were randomized to three cycles of epirubicin (E) 110 mg/m2 followed by three cycles of paclitaxel (T) 250 mg/m2 followed by three cycles of "intensified" CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) or to four cycles of E, followed by four cycles of CMF. HER-2 was assessed by immunohistochemistry (IHC) in 394 patients, and by fluorescence in situ hybridization (FISH) in cases scored as 2+ by IHC. VEGF was evaluated in 323 patients by IHC. RESULTS: HER-2 overexpression was detected in 123 patients (31%) and high expression of VEGF in 233 (72%). The rate of HER-2 overexpression was significantly higher in patients with positive VEGF staining (35% vs. 21%, p=0.02). Overexpression of HER-2 was significantly associated with negative hormonal status, high histologic grade and larger tumors. HER-2 overexpression was a significant negative predictor of DFS (p=0.002), but not of OS. Adjusting for HER-2 overexpression, DFS and OS did not significantly differ between treatment groups. Positive VEGF staining was not associated with receptor status, number of positive nodes, grade, tumor size, incidence of relapse or death. CONCLUSIONS: For both treatments, HER-2 overexpression was a significant negative prognostic factor for DFS but not for OS, while high expression of VEGF was not significantly associated to either DFS or OS. No predictive ability of HER-2 status or VEGF overexpression for T treatment was evident.
Abstract: Epidemiological, experimental and clinical data strongly support the possibility that breast cancer can be prevented by using anti-estrogenic interventions in healthy women. Four trials involving over 25,000 women have so far been reported using tamoxifen 20 mg/day or placebo in healthy women to chemoprevent breast cancer, and several trials utilizing raloxifene or aromatase inhibitors are underway. Interim analyses of the Royal Marsden tamoxifen trial and the Italian national trial showed no effect on the early incidence of breast cancer. The NSABP-P1 showed a 49% reduction in early incidence of breast cancer. This was associated with a reduction in osteoporotic fractures but increases in the risks of endometrial cancer, cataract and thromboembolism. The IBIS trial showed a 32% reduction with a two-fold increase in endometrial cancer and in thromboembolic events. Mortality rates of breast cancer in women receiving tamoxifen prophylactically should be monitored and further follow-up of these trials is needed to determine whether tamoxifen provides an overall health benefit or increase specific or overall survival of breast cancer. High-risk women should not be advised to take anti-estrogens outside of a clinical trial setting.
Abstract: Long-term endocrine therapy for breast cancer may have clinical implications as drugs that potentially alter the lipid profile may increase the risk of developing cardiovascular disease. In this study, a companion subprotocol to the ATENA (Adjuvant post-Tamoxifen Exemestane versus Nothing Applied) trial, we compared the effect of the steroidal aromatase inactivator exemestane on the lipid profile of post-menopausal women with operable breast cancer in the adjuvant setting to that of observation alone following deprivation of 5-7 years primary treatment with tamoxifen. In this open-label, randomized, parallel group study, 340 post-menopausal patients with operable breast cancer who had been treated with tamoxifen for 5-7 years were randomized to either 5 additional years of exemestane (25 mg/day; n=172) or observation alone (n=168). Assessments of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total serum triglycerides (TRG) were performed at baseline, and at 6 and 12 months. Total TRG levels were significantly reduced compared with baseline for the exemestane and the observational arm. Both total cholesterol and LDL levels were significantly increased above that of baseline values by 6 months, maintained through to 12 months, with no significant difference between the two treatment arms. There was no significant alteration observed for HDL over time or between the two arms. We conclude that sequential adjuvant treatment with exemestane in post-menopausal operable breast cancer patients following cessation of 5-7 years of tamoxifen does not appear to significantly alter the lipidemic profile for at least 12 months compared with an observational arm.
Abstract: The aim of this retrospective clinical study was the analysis of histologic findings of nonpalpable breast lesions managed by open surgical biopsy. A series of 630 women underwent 664 preoperative localizations of nonpalpable, mammographically detected breast lesions during the last 10-year period. Indications for biopsy were (1) clustered microcalcifications, (2) solid mass, and (3) radiologic parenchymal distortion. The lesions were localized preoperatively using hook-wire methods, and all biopsies were performed under general anesthesia. Histopathology revealed carcinoma in 172 (25.9%) cases; noninvasive in 114 (66.3%) cases and infiltrating in 58 (33.7%) cases. The highest malignancy rate was found in cases with microcalcifications (112 carcinomas out of 323 cases, 34.7%). Lymph node invasion was present in 25% of patients with invasive cancers. The hook-wire localization of nonpalpable breast lesions is a simple, accurate and safe method for detection of early breast cancers. Frozen section is feasible and accurate in the majority of these lesions, and therefore, diagnostic and therapeutic one-step surgical procedures could be performed.
Abstract: PURPOSE: The aim of this study was to explore the effect of dose-dense sequential chemotherapy with or without paclitaxel primarily on disease-free survival (DFS) and secondarily on overall survival (OS) in patients with high-risk operable breast cancer. PATIENTS AND METHODS: From June 1997 until November 2000, 604 patients with T1-3N1M0 or T3N0M0 tumors were randomized to three cycles of epirubicin 110 mg/m2 followed by three cycles of paclitaxel 250 mg/m2 followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) (group A), or to four cycles of epirubicin followed by four cycles of CMF, as in group A (group B). All cycles were given every 2 weeks with granulocyte colony-stimulating factor support. RESULTS: A total of 595 patients were eligible. Median follow-up was 61.7 months for group A and 62 months for group B. The 3-year DFS was 80% in group A and 77% in group B. Survival rates were 93% and 90%, respectively. The effect of treatment on the hazard of death was different according to hormonal receptor status. More specifically, in patients with negative receptor status the hazard of death was significantly higher for group B (hazard ratio 2.42). Both regimens were well tolerated and severe acute side-effects were infrequent. No cases of severe cardiotoxicity or acute leukemia were recorded. CONCLUSIONS: The present study failed to demonstrate a significant difference in DFS or OS between the two treatment groups. However, our study has shown clearly that high-dose paclitaxel can be safely incorporated to dose-dense sequential chemotherapy.
Abstract: INTRODUCTION: Long-term endocrine therapy for breast cancer may have clinical implications as drugs that potentially alter the lipid profile may increase the risk of developing cardiovascular disease. In this study, a companion sub-protocol to the TEAM (Tamoxifen and Exemestane Adjuvant Multicenter) International trial, we compared the effect of the steroidal aromatase inactivator exemestane on the lipid profile of postmenopausal women with early breast cancer in the adjuvant setting to that of tamoxifen. PATIENTS AND METHODS: In this open-label, randomized, parallel group study, 176 postmenopausal patients with estrogen and/or progesterone receptor positive early breast cancer were randomized to either adjuvant exemestane (25 mg/day; n = 90) or tamoxifen (20 mg/day; n = 86). Assessments of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and serum triglycerides (TRG) were performed at baseline and every 3 months for the first 12 months. RESULTS: Serum triglyceride levels were consistently increased above baseline throughout the study in the tamoxifen arm, while there was a trend towards reduction in the exemestane arm. There was also an overall trend for tamoxifen to decrease the levels of LDL throughout the study period. Exemestane did not demonstrate any other significant change in HDL levels; however, there was a consistent trend for a reduction in total cholesterol in both treatment arms. The atherogenic risk determined by the TC:HDL ratio remained stable in both arms throughout the treatment period. CONCLUSIONS: Exemestane appears to have a neutral effect on total cholesterol and HDL levels. Unlike tamoxifen's positive effect on LDL levels, exemestane does not significantly alter LDL levels. Tamoxifen on the other hand increases triglyceride levels, while exemestane results in a beneficial reduction in TRG levels. These data offer additional information with regard to the safety and tolerability of exemestane in postmenopausal breast cancer patients and support further investigation of its potential usefulness in the adjuvant setting.
Abstract: The aim of this study is to present two rare cases of young female patients who were under antidepressant medication and developed bilateral breast disease; histology confirmed the noninvasive, malignant nature. The role of that type of agents in the breast pathology is briefly discussed, based on the data of the current literature.
Abstract: Paclitaxel (Taxol) and carboplatin are an effective combination regimen for treating advanced breast cancer. Gefitinib (IRESSA) is the first epidermal growth factor receptor tyrosine kinase inhibitor to be approved for cancer treatment. This multicenter phase II trial treated 68 patients with advanced breast cancer with paclitaxel (175 mg/m(2) over 3 h) and 3-weekly carboplatin (area under the curve of 6) for six cycles, and 250 mg/day gefitinib orally. Median age was 57 (range 35-77) years, patients had performance status 0 (69.1%), 1 (27.9%) 2 (2.9%), 82.4% of patients had visceral metastases and 63.2% had received adjuvant chemotherapy. Forty-eight (70.6%) patients completed six cycles of chemotherapy and 20 (29.4%) patients discontinued treatment (seven [10.3%] due to disease progression, seven [10.3%] due to toxicity, five [7.4%] withdrew consent and one [1.5%] died after the first cycle). Sixty-three (92.7%) patients were evaluable for response; nine (13.2%) had complete responses, 30 (44.1%) had partial responses, 21 (30.9%) had stable disease and three (4.4%) had disease progression. Grade 3/4 adverse events in > or =5% of patients except of alopecia, included neutropenia (17.7%), anemia (10.3%), diarrhea (7.4%), thrombocytopenia (5.9%) and peripheral neuropathy (5.9%). Of those tumor biopsies available for immunohistochemical analysis (n=60), 5.0% were positive and 35.0% negative for expression of all HER-family receptors. Comparable numbers of tumor biopsies were nuclear p27(kipl) positive and negative (39.7 and 42.7%, respectively), with the majority (72.1%) negative for cytoplasmic p27(kipl). The observed efficacy data in this study were similar to those reported for the combination of paclitaxel and carboplatin alone.
Abstract: Ten cases of Mondor's disease of the breast (9 females, 1 male) are described. The diagnosis was based mainly on clinical examination, while breast imaging, used in five cases, was complementary. Most of our cases (9) had complete restoration of the thrombosed subcutaneous breast vein, either spontaneously (4), or after anti-inflammatory medication (5). Only one of our patients had surgical management (vein excision) due to delayed remission. None of our cases was related to breast cancer.
Abstract: The current study was designed to evaluate the prevalence of BRCA1 and BRCA2 germline mutations in Greek moderate- and low-risk individuals with respect to clinicopathological phenotype and clinical outcome of breast cancer. Ninety-four consecutive individuals were prospectively recruited from two University Breast Cancer Clinics (Hippokrateion Hospitan and Laikon Hospital) between 1989 and 1999 and were categorized as moderate-risk and low-risk individuals for carrying BRCA1/2 germline mutations. To identify the underlying mutations, protein-truncation test and single-strand conformation polymorphism methods were used, followed by direct sequencing. Three novel BRCA1 missense mutations, one novel BRCA1 intronic deletion, three novel (previously reported) BRCA2 truncating mutations, and one novel BRCA2 missense mutation were identified in the moderate-risk group of individuals studied. The BRCA1/2 missense mutations as well as the single intronic variant identified were designated as unclassified genetic variants. Two BRCA1 unclassified genetic variants (missense mutations) were detected in two of the three (66.7%) male breast cancer patients analyzed, while the third one was identified in a sporadic (low-risk) breast cancer patient. Clinicopathological characteristics of breast carcinomas originating from BRCA1/2 heterozygotes were consistent with those already reported and not different from those observed in BRCA1/2 mutation (-) breast cancer patients. Furthermore, BRCA1/2 mutation carriers presented an excellent 4.5-year overall survival (100%). Our results reveal the unique characteristics of BRCA1/2 mutation status, genotype-phenotype correlations, and prognosis, in moderate- and low-risk individuals of Greek ancestry. Breast cancer due to mutations in BRCA1 and BRCA2 genes appears to be a heterogeneous syndrome in the Greek population.
Abstract: Mammographically missed breast cancers remain a major medical and legal issue. In order to clarify causes and methods of the limitations, we present the experience of our Unit on this field. During the years 1999 and 2000, 319 breast cancer patients were admitted for surgical treatment to our Unit. Their files were reviewed in order to identify cases with mammography-related delayed diagnosis. Thirty-three cases of mammographically missed cancers were found (10.3%). The usual reasons for the delayed diagnoses were: retrospectively visible cancers, in benign looking lesions no further action was taken, and lesions with a rather malignant appearance were reported as benign. Missed cancers could be reduced by simple measures such as the full assessment of breast patients with clinical, radiologic, and cytologic-histologic evaluation, the double screening of mammograms, and improvement of the mammographic equipment and technique.
Abstract: Adiponectin, an adipocyte-secreted hormone, is closely and inversely associated with insulin resistance and was recently found to be inversely and independently associated with endometrial cancer. Because insulin resistance in the setting of obesity has also been associated with the development of breast cancer, we have hypothesized that decreased adiponectin levels might underlie the association between breast cancer and obesity/insulin resistance. We evaluated the association of adiponectin with the occurrence of breast cancer in a case-control study comprising 174 women with newly diagnosed, histologically confirmed breast cancer and 167 controls. We found an inverse, fairly strong, and statistically significant association of serum adiponectin with breast cancer (odds ratio, 0.84; 95% confidence interval, 0.71-0.99). Importantly, despite a fairly robust inverse association of adiponectin with breast cancer risk among postmenopausal women (odds ratio, 0.82; 95% confidence interval, 0.67-1.00), no such significant association between adiponectin and breast cancer was found among premenopausal women. The observed associations were independent of possible effects of major components of the IGF system, leptin, body mass index, sociodemographic variables, and known risk factors for breast cancer. Future studies are needed to prove causality and provide further insights into both the mechanisms underlying the actions of this hormone and its potential role in breast cancer.
Abstract: PURPOSE: To evaluate the association between mammographically detected arterial calcifications and systemic vascular disease. MATERIAL AND METHODS: The medical records of 77 women who had either breast arterial calcifications or underwent surgery for carotid stenosis, abdominal aortic aneurysm, or femoropopliteal bypass (study groups A and B) were evaluated and compared with 33 women without breast arterial calcifications (group C). Patients in both arms of the study underwent additional vascular tests or mammography. RESULTS: Currently available data indicate that there is a statistically significant correlation between the presence of arterial calcifications on the mammogram and atheromatosis of the carotid or femoral arteries. CONCLUSION: Screening mammograms might be useful in the detection of women at risk for systemic vascular disease.
Abstract: BACKGROUND: In contrast to autopsy findings, solitary splenic metastases from solid tumors are extremely rare. It may occasionally be the first manifestation of recurrent solid cancers, and in particular of gynecologic malignancies. Secondary amyloidosis is also found in malignancy. CASE: A 52-year-woman originally diagnosed with a Stage IB, grade 2 endometrial carcinoma presented two and a half years later with a paroxysmal non-productive cough, weakness, loss of appetite and daily afternoon fever. On clinical examination wheezing on forced exhalation and painful splenomegaly was found. After an extensive work-up the patient underwent an explorative laparotomy and a splenectomy was performed. Histologic examination showed solitary spleen metastasis with amyloidosis. All symptoms resolved. As the patient had received a full course of postoperative irradiation after a total abdominal hysterectomy, six cycles of combination chemotherapy were administered. The patient remains free of recurrence, 46 months later. CONCLUSION: A case of solitary spleen metastasis with amyloidosis in a patient with endometrial cancer is presented.
Abstract: PURPOSE: The experience of our Breast Unit in the diagnosis and treatment of fibroadenomas is presented in this retrospective study, focusing specifically in cancer development within these common benign tumors of young age. MATERIAL-METHODS: 310 women with histologically verified breast fibroadenomas who had surgical management in our Unit over the last 14 years were included in the study. RESULTS: Most of them (n: 255) presented with palpable lesions and had triple assessment preoperatively, while the remaining 55 had nonpalpable lesions and underwent needle-wire localization biopsies. Nine cases had cancer development, usually in situ, within the fibroadenomas (2.9%). CONCLUSION: Coexistence of fibroadenomas and breast cancer is relatively rare, but it should not be ignored by breast surgeons, and patients should be properly informed.
Abstract: This phase II trial studied the efficacy and toxicity of full dose paclitaxel plus vinorelbine, as salvage chemotherapy in patients with metastatic breast cancer resistant to anthracyclines. Patients received vinorelbine (30 mg/m2) followed 1 hour later by full dose paclitaxel (175 mg/m2) every 3 weeks for a maximum of 8 cycles or until disease progression. Because of the heavy pretreatment of the patients, prophylactic granulocyte-colony stimulating factor (5 microg/kg) was administered daily for 5-10 days. To minimize potentially cumulative neurotoxicity due to both agents, amifostine was given prior to chemotherapy. Thirty-four patients: 8 with tumors primary resistant and 26 with tumors recurring within 3-6 months after anthracycline treatment, were evaluable for efficacy and toxicity. Objective responses occurred in 11 patients [32%; 95% confidence interval (CI): 16.3-47.7%), all partial responses. Responses were observed in lung and liver. The median response duration was 4 months (range 3-7), median time to progression was 5 months (range 3-9) and median overall survival was 8 months (range 4-24). Neutropenia was dose limiting (35% grade 3-4 toxicity). The left ventricular ejection fraction, measured and followed in 18 patients, fell less than 20% below baseline level in 9 patients (50%), but only one patient developed congestive cardiac failure. The paclitaxel-vinorelbine regimen was moderately tolerated and moderately effective in poor prognosis breast cancer patients with visceral metastases and tumors resistant to anthracyclines. The combination at these doses and schedules should be considered in the design of regimens for advanced breast cancer.
Abstract: Carcinosarcoma is a rare, malignant tumor of the breast, consisting of intraductal or infiltrating carcinoma contiguous or subtly merged with a highly cellular, mitotically active pleomorphic spindle cell stroma (sarcoma). It is a form of the metaplastic mammary carcinomas and it is probably derived of myoepithelial cells. We report two cases of breast carcinosarcoma in two white women. The patients, following a frozen section positive for malignancy, had had a modified radical mastectomy. Paraffin sections and positive immunohistochemical cell staining (in our first case) confirmed the diagnosis of carcinosarcoma. This tumor should be distinguished from other forms of metaplastic carcinomas because it is very aggressive and has an ominous prognosis.
Abstract: This phase II trial studied the efficacy and toxicity of docetaxel-epirubicin, supported by granulocyte colony-stimulating factor, as first-line chemotherapy in metastatic breast cancer. Patients received epirubicin (60 mg/m2) followed 1 hour later by docetaxel (80 mg/m2) every 3 weeks for a maximum of 8 cycles or until disease progression. Prophylactic granulocyte colony-stimulating factor (5 micrograms/kg) was administered daily for 5 days. Sixty-nine patients were evaluable for efficacy and toxicity. Objective responses occurred in 45 patients (65%; 95% confidence interval: 53-76%), with 11 (16%) complete responses and 34 (49%) partial responses. Responses were observed at all metastatic sites. The median response duration was 8 months (range 4-68), median time to progression was 10 months (range 4-68) and median overall survival was 24 months (range 7-68): neutropenia was dose limiting (46% grade 3-4 toxicity). The left ventricular ejection, fraction measured in 50 patients, fell below normal in 14 patients (28%), 8 patients had grade 1 and 6 grade 2 cardiotoxicity, but none developed congestive cardiac failure. The docetaxel-epirubicin regimen is extremely effective in poor prognosis breast cancer patients with visceral metastases, with significant overall and complete responses, followed by prolonged survival in responders. Although myelosuppression remains the major toxicity, prophylactic GCSF administration was associated with a small percentage of neutropenic fever.
Abstract: We investigated endotumoral and peritumoral lymphocytic subsets [natural killer cells (NK), B-cells and cytotoxic/suppressor (CD(8)+) T-cells], and expression of MUC1 and MUC6 glycoprotein with regard to various clinicopathological parameters in invasive breast cancer tissues. The study population consisted of 64 female patients with invasive ductal breast cancer of not-otherwise-specified type. Thirty-five women with benign breast lesions served as controls. High-grade carcinomas exhibited higher numbers of endotumoral NK cells and B-cell aggregates than the rest of the tumors examined (P=0.0003 and 0.027, respectively). Cases with more than three positive lymph nodes and with tumors over 2 cm in diameter exhibited higher numbers of endotumoral NK cells (P=0.047 and 0.023, respectively). Increased numbers of peritumoral CD(8)+ T-cells were detected in cases with lymph node metastases (P=0.045). MUC1 was expressed with weaker staining intensity in the control group than in the group with breast cancer (P=0.011). Grade III carcinomas exhibited significantly stronger expression of MUC6 glycoprotein (P=0.001) than the control group. In conclusion, tumors with markers of poor prognosis exhibited increased numbers of lymphocytic infiltrates, and of NK cells in particular, and stronger MUC1 and MUC6 glycoprotein immunoreactivity than did the other tumors.
Abstract: PURPOSE: Presentation of the results of Tc-99m-sestamibi imaging in the pre-operative localization of parathyroid adenomas and the intra-operative localization of those lesions using a gamma detector (prospective study). PATIENTS & METHODS: Eighteen consecutive patients aged 27-75 years with primary hyperparathyroidism (PHPT) underwent Tc-99m-sestamibi scanning 1-2 hours before the operation and the presence of a single adenoma was recognized. All our patients underwent bilateral neck exploration based on pre-operative scanning and intra-operative gamma detector guidance and the adenoma was detected in the positions shown by both methods. RESULTS: In 16 patients we found a single adenoma localized in the same position shown by pre-operative scanning, while the intra-operative method accurately revealed all abnormal glands. In one of the two patients where an inaccurate pre-operative localization technique had been carried out, we performed thyroid lobectomy (the adenoma proved to be intrathyroidal), while the other one had an adenoma which was not close to the site indicated by the pre-operative scintigraphy. Serum calcium reverted to normal within a few days postoperatively. CONCLUSION: Patients with true-positive scans for single parathyroid adenoma could be eligible for minimally invasive operations since the abnormal gland is easily identified by the above-mentioned methods.
Abstract: PURPOSE: To evaluate of a computer-aided method for differentiating malignant from benign clustered microcalcifications. MATERIAL AND METHODS: Our material was 350 suspicious microcalcifications on mammograms from 330 female patients who underwent breast biopsy (after hook wire localization and under mammographic guidance). The histologic findings were malignant in 140 cases (40%) and benign in 210 cases (60%). Those clusters were manually detected, computer-aided analyzed and quantitatively estimated. Besides computer analysis, 3 physicians-observers (2 radiologists and 1 breast surgeon) evaluated the malignant or benign nature of the clustered microcalcifications. The performance of the artificial network, each observer and the three observers as a group was evaluated by receiver operating characteristics (ROC) curves. RESULTS: Comparison of the ROC curves revealed the following AUC values (area under the curve): computer - 0.950, physician 1 - 0.815, physician 2 - 0.830, physician 3 - 0.830, and physicians as a group - 0.825. The results, compared by the student t-test for paired data, showed a statistically significant difference between computer analysis and physicians' performance, independently and as a group. CONCLUSION: Our study showed that computer analysis achieved statistically significantly better performance than that of physicians in the classification of malignant and benign calcifications.
Abstract: Both primary and secondary gallbladder melanomas are rare and, when a solitary melanoma is found in the gallbladder, it is difficult to determine if it is primary or metastatic disease. We report the case of a young woman found to have a single metastatic gallbladder melanoma. Surgical removal of a solitary metastatic focus remains the treatment of choice for isolated metastasis of a malignant melanoma; however, the effectiveness of complementary chemotherapy and immunotherapy is still being examined.
Abstract: BACKGROUND: The cyclin-dependent kinase inhibitor p27 plays a central role in cell cycle progression and is deregulated in breast carcinomas. Although its levels are inversely associated with tumor proliferation, overexpression of p27 has been reported in a subset of rapidly proliferating breast carcinoma cell lines. METHODS: p27 levels were determined by immunohistochemistry in a series of 52 sporadic invasive breast carcinomas consisting of 47 ductal, 2 lobular, and 3 mixed; most tumors were Grade 2 or 3 (46 of 52) and Tumor Node Metastasis (TNM) Stage II-IV (46 of 52). E-cadherin expression and its gene alterations at 16q22.1 were also studied, because in vitro evidence suggests a biologic association between p27 and E-cadherin-mediated growth suppression. RESULTS: The mean p27 labeling index (LI; percentage of p27 positive tumor cells) was 33.3% +/- 25.3% (range, 0.1-85%). High p27 levels (p27 LI, > 50%) were observed in 14 (26.9%) of 52 carcinomas and were significantly associated with metastatic disease in axillary lymph nodes (14 of 33 vs. 0 of 19; P = 0.0007 by Fisher exact test). In addition, p27 LI was higher in the group of lymph node positive vs. lymph node negative tumors (mean p27 LI, 40.9% vs. 20.1%; P = 0.008 by Mann-Whitney test). Reduced or absent E-cadherin expression was found in 27 of 45 (60%) informative cases. Allelic imbalance of the 16q22.1 locus was found in 14 (27.5%) of 51 cases by using the microsatellite markers D16S503, D16S752, and D16S512. p27 LI and E-cadherin alterations were not statistically related. CONCLUSIONS: In summary, high p27 levels detected in a subset of advanced breast carcinomas correlate with lymph node metastasis, suggesting that other mechanisms may bypass the cell cycle inhibitory role of p27 and provide growth advantage in these tumors.
Abstract: Local recurrence of colorectal cancer after curative surgery is a major clinical problem. The aim of our study was to present our experience in this field. Between January 1990 and December 2000, 572 patients underwent resection for colorectal cancer in our department; 66 of them had local recurrence within the first 2 years. Most of those patients had Dukes' stage B (n = 24) or stage C (n = 37) tumors, which were located mainly in the rectum (n = 40) and sigmoid colon (n = 18). The incidence of local recurrence was 11% and 15.9% for tumors that were Dukes' stages B and C, respectively. Thirty-five of 66 patients received palliative treatment, and 28 of them died within 9 months. The remaining 31 patients underwent radical excision of the recurrent tumor: 11 of these patients died within 2 years, and 20 were still alive after 30 months. The only hope for long-term survival for patients presenting with local recurrence from colorectal cancer after primary radical treatment is to identify local recurrence at an early stage and treat it in a radical manner.
Abstract: Cystic breast masses are very common in female patients attending breast clinics. Most of them are benign and managed by simple aspiration. We reviewed histology records for the last 12 years to find patients with cystic breast carcinomas and to evaluate special clinical signs that may help to identify patients with this rare entity. Eighteen patients with cystic breast carcinomas were found among 1510 new breast cancer patients (1.19%) who were seen at our Breast Unit during this period. Ten had intracystic papillary carcinoma (0.66% of all breast cancers), seven had cystic degeneration of ductal carcinoma, and one had a mucinous carcinoma. The diagnosis of intracystic papillary carcinoma was based on cyst fluid cytology and breast imaging in most patients and on open breast biopsy in two cases only. The prognosis of our cystic breast carcinoma patients was excellent regardless of the specific histologic type of the tumor. We conclude that cysts in postmenopausal women should be viewed with suspicion. Bloodstained aspirated cyst fluid should be sent for cytology and breast imaging should be carried out in all these cases. Residual mass after cyst aspiration is also an indication for open biopsy.
Abstract: Family history is a well-recognized risk factor for the development of breast cancer. The isolation of BRCA1 and BRCA2 genes, the two major predisposing genes in familial and to early onset breast and ovarian cancer, has resulted to the identification of a large number of families with mutations in these two genes. Despite the large number of distinct mutations detected in both genes, several mutations have been found to recur in unrelated families of diverse geographical origin. We have analyzed 27 Greek patients with familial breast cancer the majority of those having one first and one second degree relatives affected and 28 patients with sporadic breast cancer for BRCA2 germline mutations. The techniques used were single-strand conformation polymorphism analysis (SSCP) followed by sequencing. Furthermore, the clinical presentation and prognosis of BRCA2 associated breast cancer cases was compared to 20 adequately matched for age and date of diagnosis (within one year) sporadic breast cancer patients. We identified three novel BRCA2 mutations (3058delA, 6024delTA, and 4147delG) in the ovarian cancer cluster region (OCCR) and one already known (2024del5) germline BRCA2 gene mutation in five different breast cancer families. The 4147delG mutation was detected in two unrelated patients. BRCA2 germline mutations were correlated with early-onset breast cancer RR=4.77 (95% CI: 0.666-34.463). Although patients with BRCA2 germline mutations did not have a distinct histological phenotype they had an improved overall survival (100% vs 65%). Our findings suggest that there is a cluster of novel mutations in exons 10 and 11 in Greek patients with familial breast cancer. These mutations appear to have a milder clinical phenotype when compared to the rest of the study group.
Abstract: BACKGROUND: To determine the activity and safety of the combination of paclitaxel and pegylated liposomal doxorubicin (Caelyx) in patients with locally advanced breast cancer. PATIENTS AND METHODS: This was a multicenter phase II study. Thirty-five newly diagnosed patients with locally advanced breast cancer were included in the study. Histological or cytological diagnosis was necessary for inclusion. Median age was 54 years (range 26-73 years). Fifteen patients were premenopausal and 20 postmenopausal. Paclitaxel was administered at a dose of 175 mg/m(2) and pegylated liposomal doxorubicin 35 mg/m(2) every 3 weeks for six cycles. RESULTS: Twenty-five patients (71%) responded. Six (17%) had a complete response, 19 (54%) had a partial response, four remained stable, two progressed and four were not evaluated for response due to discontinuation of chemotherapy. Three patients had a pathologically complete response. A total of 173 cycles were administered. The primary toxicity observed was skin toxicity. Grade 3 skin toxicity was noted in four patients (11%). Palmar-plantar erythrodysesthesia (PPE) grade 3 was experienced by three (9%). Two patients presented with PPE and skin toxicity. Hematological toxicities included grade 3 leukopenia in four patients (3%). Other grade 3 toxicities were uncommon and included only alopecia in 29 patients (83%). Grade 3 or 4 neurotoxicity was not observed in any patient. Dose reduction was necessary in seven patients; in six due to skin toxicity and in one due to neutropenia. Four patients discontinued treatment due to skin toxicity. There were no treatment-related deaths. CONCLUSIONS: The combination of pegylated liposomal doxorubicin and paclitaxel was active in locally advanced breast cancer. The primary toxicity was cutaneous toxicity and it was manageable.
Abstract: Granular cell tumor (GCT) is an uncommon, usually benign tumor that occasionally involves the breast. It is possibly of neural origin (Schwann cells) and usually occurs in premenopausal black women. Physical examination, mammographic, ultrasonographic findings and pathologic examination may suggest breast malignancy. Positive immunohistochemical staining of the cells for S-100 protein, NSE, and CEA is indicative of GCT. Surgical treatment of choice is wide local excision. We report a case of granular cell tumor of a female breast. A 52-yr-old white woman had a palpable mass close to her right axilla. Computer tomography (CT) showed a 3.74 cm mass in the mammary tail of Spencer. The findings were suspicious for malignancy and the lesion was widely resected. Pathologic examination showed granular cell tumor.
Abstract: BACKGROUND: Breast cancer is characterized by complex genetic alterations found in multiple chromosomal regions, most commonly losses of 17p, 16q, 8p and others. A number of tumor suppressor genes mapped on these loci have been investigated in mammary tumors, whereas other gene products are of unclear function and await identification. MATERIALS AND METHODS: We analyzed the loss of heterozygosity (LOH) of two chromosomal loci: a. 16q24.3 using the genetic markers D16S303, D16S3026 and D16S3407 and b. 16q22.1, the locus of E-cadherin gene, using the microsatelite markers D16S503, D16S752 and D16S512, in a series of 63 sporadic invasive breast carcinomas consisting of 56 ductal, 4 lobular and 3 tumors of mixed type. Our findings were correlated with proliferative activity, ploidy and hormonal status of the tumors. RESULTS: Fourteen (22.2%) tumors demonstrated LOH of 16q24.3. Allelic imbalance of the 16q22.1 locus was found in 19 of 61 informative cases (31%) and commonly coexisted with LOH of 16q24.3. A significant association was observed between LOH of D16S752 and the absence of progesterone receptors in tumor cells (p = 0.005). CONCLUSIONS: LOH of 16q24.3 and 16q22.1 are frequent genetic alterations in breast cancer and they do not seem to correlate with tumor cell proliferation or ploidy. The statistical association between LOH of 16q24.3 and progesterone receptors need to be further investigated in larger series.
Abstract: Ectopic breasts usually develop along the mammary ridges. Their incidence has been reported as up to 5-6%. Development of malignancy is rare. We report three cases of postmenopausal female patients with breast cancer which developed in the axillary accessory breast. They were all successfully treated by surgery and adjuvant therapy. A review of the literature on the incidence and pathology of ectopic mammary tissue is also presented.
Abstract: INTRODUCTION/OBJECTIVE: The purpose of this study was to evaluate a computer based method for differentiating malignant from benign clustered microcalcifications, comparing it with the performance of three physicians. METHODS AND MATERIAL: Materials for the study are 240 suspicious microcalcifications on mammograms from 220 female patients who underwent breast biopsy, following hook wire localization under mammographic guidance. The histologic findings were malignant in 108 cases (45%) and benign in 132 cases (55%). Those clusters were analyzed by a computer program and eight features of the calcifications (density, number, area, brightness, diameter average, distance average, proximity average, perimeter compacity average) were quantitatively estimated by a specific artificial neural network. Human input was limited to initial identification of the calcifications. Three physicians-observers were also evaluated for the malignant or benign nature of the clustered microcalcifications. RESULTS: The performance of the artificial network was evaluated by receiver operating characteristics (ROC) curves. ROC curves were also generated for the performance of each observer and for the three observers as a group. The ROC curves for the computer and for the physicians were compared and the results are:area under the curve (AUC) value for computer is 0.937, for physician-1 is 0.746, for physician-2 is 0.785, for physician-3 is 0.835 and for physicians as a group is 0.810. The results of the Student's t-test for paired data showed statistically significant difference between the artificial neural network and the physicians' performance, independently and as a group. DISCUSSION AND CONCLUSION: Our study showed that computer analysis achieves statistically significantly better performance than that of physicians in the classification of malignant and benign calcifications. This method, after further evaluation and improvement, may help radiologists and breast surgeons in better predictive estimation of suspicious clustered microcalcifications and reduce the number of biopsies for non-palpable benign lesions.
Abstract: p53 protein expression and oestrogen and progesterone receptor status in invasive ductal breast carcinomas The p53 protein expression and oestrogen and progesterone receptors status was investigated in correlation to the grade of malignancy of primary breast carcinomas. Our material constituted imprints from surgical biopsies of 75 invasive ductal breast cancer cases. The p53 protein expression was investigated immunocytologically using the monoclonal antibody p53 DO-7 (DAKO). A biochemical DCC method was applied for the detection of oestrogen and progesterone receptors for all tumours. Fifty-one percent of breast cancer cases were p53 protein positive. A statistically significant association of p53 protein expression and high tumour grade was found (chi2=23.72, d.f.=2, P < 0.001). A statistically significant association was also found between oestrogen and progesterone receptor positive cases and the grade of malignancy (P < 0.001). A negative association between p53 protein expression and oestrogen (ER) and progesterone receptors (PgR) positivity was found. From our results it appears that it is possible to distinguish from grade II tumours two subgroups of cases, one with low malignancy potential and p53 (-), ER (+), PgR (+), and another subgroup with high malignancy potential and phenotype p53 (+), ER (-), PgR (-). The last subset of patients could actually benefit from adjuvant therapy.
Abstract: AIMS: Estimation of prevalence of autoimmune thyroid disorders in Greek breast cancer patients (prospective study). METHODS: The prevalence of autoimmune thyroiditis was estimated in 310 Greek breast cancer patients, in 100 women with benign breast disease and in 190 women without any breast disease, by submitting them to clinical examination, ultrasound thyroid evaluation, serum thyroid antibody determination and fine needle aspiration (FNA) of the thyroid gland. RESULTS: Autoimmune thyroiditis was found in 136/310 (43.9%) breast cancer women: 95 were diagnosed by positive autoantibodies, 19 had positive FNA findings and 22 had both positive autoantibodies and positive FNA findings. In 117 cases, thyroid autoantibodies were positive (37.7% whereas the control groups had respective rates of 19% and 18.4% autoantibody positivity). CONCLUSIONS: There is evidence of high incidence of autoimmune thyroiditis in Greek breast cancer patients, increasing in relation to cancer stage.
Abstract: The purpose of this study was to determine factors associated with the incidence of axillary lymph node metastases (ALNM) in T1 tumors and cases in which axillary dissection could be omitted. Data from 195 patients with T1 primary invasive breast cancer (size < or = 2 cm) who underwent either mastectomy or wide local excision of the tumor and axillary dissection were reviewed. ALNM was found in 59 of 195 patients with T1 tumors (30.3%). Tumor size was found to be the only independent predictor of ALNM, having a directly analogous relationship with the probability of invaded nodes: T1a (< or = 5 mm) tumors had 0 per cent ALNM, whereas T1b (5 mm < T1b < or = 10 mm) and T1c (10 mm < T1c < or = 20 mm) tumors had 25.7 per cent and 33.8 per cent ALNM respectively. Among the other factors studied (patient age, tumor site, hormone receptor status, histologic type, and grade of the tumor) only the histologic grade of the tumor cells appeared to correlate with the incidence of lymph node involvement, but this was not statistically significant. In conclusion only tumor size has statistically significant correlation with the incidence of ALNM. Routine axillary dissection could be omitted only in patients at minimal risk of ALNM (ductal carcinoma in situ and T1a) and when treatment decisions were not influenced by lymph node status (e.g., elderly patients with clinically negative axilla). Axillary dissection (at least levels I and II) should be performed in all cases with primary invasive breast cancer with tumor size > 5 mm.
Abstract: OBJECTIVES: Because both breast cancer and the hormone leptin are associated with obesity and reproductive phenomena in women, we have examined whether there is a relationship between leptin and breast cancer among premenopausal and postmenopausal women. We have also evaluated in this dataset the association of IGF-I with breast cancer. METHODS: Seventy-five cases, diagnosed during mammographic screening, with incident breast cancer were matched for age and type of permanent residence with seventy-five controls from those screened negative in the same study base. RESULTS: There was no evidence for an association between IGF-I and either premenopausal or postmenopausal breast cancer risk or between leptin and postmenopausal breast cancer. Among premenopausal women, however, there was a strong and statistically significant inverse association of leptin with breast cancer. CONCLUSION: We did not confirm the positive association, reported from other investigations, of IGF-I with premenopausal breast cancer risk. We have found evidence, however, that leptin may be inversely related to breast cancer risk among premenopausal women. The latter finding is not biologically implausible and deserves to be examined in additional datasets.
Abstract: Four cases of radial scar of the breast, primarily diagnosed as carcinoma are presented; the patients were found among 858 patients who were operated on at our Breast Unit over the last 4 years. The lesion was revealed on routine mammographic examination in 4 of our patients, while in the fourth it was found by palpation. In two of our patients mammographic examination revealed architectural distortion, in one patient micro-calcifications and in the fourth patient a stellate lesion was found. In the last two patients the lesion was localized before surgery with a hook wire. Diagnosis was established by histopathologic examination in all cases. The surgeon, the radiologist and the pathologist should be aware of this clinical entity which, in spite of its benign character, has the ability to simulate invasive carcinoma clinically, mammographically and histopathologically.
Abstract: A series of 151 women underwent 156 preoperative localizations of nonpalpable, mammographically detected breast lesions. Indications for biopsy were (1) a cluster of more than five fine microcalcifications; (2) a solid lump found by ultrasound investigation; and (3) a radiologic abnormality of the breast parenchyma. The lesions were localized preoperatively using the hook-wire method (Frank needle), and all biopsies were performed under general anesthesia. Carcinoma was discovered in 34 (21.8%) cases; in 22 (64.7%) it was a noninvasive cancer (9 with microinvasions) and in 12 (35.3%) an invasive carcinoma with a mean tumor diameter of 0.8 cm. The highest malignancy rate was found among those with microcalcifications (21 of 81 cancers, or 25.9%). Lymph node involvement was seen in 25% of patients with invasive carcinomas. In conclusion, the needle localization of nonpalpable breast lesions is a simple, accurate method for early detection of small cancers with favorable prognosis.
Abstract: We report a rare case of submandibular salivary gland carcinosarcoma ('true' malignant mixed tumour) which occurred in a 77-year-old man. Microscopic examination showed a neoplasm comprised of sarcomatous elements (chondrosarcoma, rhabdomyosarcoma and osteosarcoma) with tabular salivary ductal adenocarcinoma. A short review of the literature is also presented and the poor prognosis of these tumours, in spite of complete surgical removal and additional radiation therapy and chemotherapy, is discussed.
Abstract: This cytogenetic study deals with cell material obtained from 15 pleural fluids from 11 patients with breast cancer and 27 ascitic fluids from 16 patients with ovarian cancer; in addition, 8 pleural, 5 ascitic, and 1 pericardial fluid from patients with tuberculosis, liver cirrhosis, and heart insufficiency, were studied. Using mainly direct methods, as well as short-term cell cultures, the chromosome spreads were GTG-banded. Cancerous biopsies showed a plethora of numerical and structural chromosome anomalies and exhibited broad aneuploidy. Chromosomes participating more often in numerical and structural aberrations were 1, 3, 6, 7, 8, 9, 11, 12, and 17. This study provides further cytogenetic evidence for the involvement of these chromosomes in breast and ovarian malignancy.
Abstract: In 42 postmenopausal women with breast cancer, aged 48-85 years (mean age 62.4 years) serum thyroid hormone concentrations were measured before and after 6 months of tamoxifen therapy (20 mg daily). In particular triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyroxine-binding globulin (TBG) and thyroid-stimulating hormone (TSH) concentrations before and 30 minutes after thyrotrophin-releasing hormone (TRH) administration (200 microg i.v.) were measured before and 6 months after tamoxifen therapy. T3 and T4 concentrations increased significantly (p<0.001 and p<0.05, respectively) whereas FT3 and FT4 remained unchanged (p>0.05), TBG increased significantly (p<0.001) and basal TSH concentrations as well as TSH response to TRH injection increased significantly (p<0.05) after tamoxifen therapy. It is concluded that tamoxifen administration changes thyroid hormone concentrations. However free thyroid hormone levels remain unchanged and the patients remain euthyroid after long-term tamoxifen therapy.
Abstract: OBJECTIVE: To investigate p53 protein expression in imprints from benign and ductal breast carcinoma cases in relation to the histologic grade of malignancy and clinical stage. STUDY DESIGN: The study group consisted of 60 cases of primary ductal breast carcinomas and 20 benign lesions. For the demonstration of p53 protein expression, an immunocytochemical avidin-extravidin complex technique was applied. Monoclonal antibody p53 was used as the primary antibody, diaminobenzidine as the chromogen and hematoxylin as the counterstain. RESULTS: Forty-five percent of breast cancer cases showed positive expression of p53. A statistically significant difference in p53 protein expression was observed between grade 1, 2 and 3 carcinomas and stage I, II and III cases. All benign lesions were negative for p53 protein expression. CONCLUSION: Immunocytochemical p53 protein expression in cytologic material is a simple method that can be applied in routine cytologic laboratories for the identification of genetic alterations in primary ductal breast cancer.
Abstract: We report a case of meningioma subsequently developed in a patient with bilateral breast carcinoma, which was originally thought to be single brain metastases. A brief review of the literature is presented with emphasis on the unique association between the two neoplasms, which suggests a possible hormonal relationship. The knowledge of this association is important in the differential diagnosis of patients with breast cancer who develop central nervous system manifestations.
Abstract: The p16-pRb pathway represents a vital cell-cycle checkpoint. In the present study we investigated the alterations of this G1-phase protein pathway using immunohistochemical and molecular methods in a series of 55 breast carcinomas and correlated the findings with clinicopathological features of the patients. Furthermore, we examined its relationship with the status of the chromosomal region 9p21-22 performing a deletion map analysis because there are indications that, in addition to CDKN2 and MTS2/p15(INK4B) tumor suppressor genes (TSGs), this area harbors other TSG(s). Aberrant expression (Ab) of p16 and pRb was observed in 26 (47%) and 16 (29%) of the carcinomas, respectively. A statistical trend pointing out an inverse relationship between p16 and pRb expression was found (p = 0.079). Analysis of the region that encodes for p16 by deletion mapping, a PCR-based methylation assay and PCR-SSCP, revealed that deletions and transcriptional silencing by methylation might represent the main mechanisms of CDKN2/p16(INK4A) inactivation in breast carcinomas. The results of deletion mapping also suggest that another TSG(s) may reside at the 9p21-22 area particularly at the D9S162 loci and that co-deletion of this putative gene with CDKN2/p16(INK4A) may play a role in breast carcinogenesis. In addition, microsatellite instability (MI), a marker of replication error phenotype (RER+), was observed with a frequency of 16% in the area examined and was inversely related with loss of heterozygosity (LOH). Interestingly, most cases with MI at the region encoding for p16 were aggregated in a subgroup of breast carcinomas with no other obvious genetic and/or epigenetic CDKN2/p16(INK4A) alterations. We speculate that there is an additional mechanism of CDKN2/p16(INK4A) inactivation. The relationship of p16 protein level pRb, status, the p16-pRb combined immunoprofiles, and the microsatellite alterations detected at the 9p21-22 locus with the patients' clinicopathological parameters revealed two significant correlations: one between normal pRb expression and lymph node involvement (p = 0.0263), and the other between microsatellite alterations (LOH and or MI) and tumor size (p = 9.2 x 10(-3)). In view of the heterogenous nature of breast cancer, we suggest that in a significant proportion of breast carcinomas, deregulation of the p16-pRb pathway in association with another, as-yet unidentified, TSG(s) of the 9p21-22 region may play a role in initiating or progressing the oncogenic procedure, while in other subgroups, alternative molecules may play this role.
Abstract: The prognosis of breast cancer is of major clinical importance and several histopathological, biochemical and immunological variables have been reported to be useful prognostic factors. In the present study, we investigated the clinical significance of the levels of alpha-thymosins in relation to established prognostic factors, both in breast cancer and non-malignant breast lesions, alpha-thymosin levels were measured in breast tissue extracts by specific radioimmunoassays (RIAs) developed for human prothymosin alpha (ProT alpha) and parathymosin alpha (ParaT alpha) and were found to be significantly higher (up to 17.2-fold) in malignant but not in benign breast lesions, as compared to the values of the neighbouring tissues. When alpha-thymosin levels of the tumor samples were correlated with various known prognostic parameters a statistically significant correlation (p < 0.05) was observed between the levels of ProT alpha in malignant tissues to the grade of cancer and the lymph node status of the patient. An association between ProT alpha levels with increase in risk of death from breast cancer was also noticed. These results suggest that the expression of alpha-thymosins in human breast cancer a) depends on the proliferation status of the tumor, b) associates with established prognostic factors describing the metastatic potential of the tumor and c) is related to the overall survival of the patient. The fact that such relationships hold only for cancer tissues encourages the future use of alpha-thymosins as potent prognostic factors in breast cancer.
Abstract: Mucoepidermoid carcinomas are very rare breast tumors. The morphology of this breast tumour is similar to its counterpart in the salivary gland. The first two cases reported were low-grade and neither patient had metastatic disease. Furthermore, none of the five patients with low-grade mucoepidermoid carcinoma reported by Fisher had axillary lymph node involvement and were alive with no evidence of disease 4 to 10 years after diagnosis and were considered of probable favourable prognosis. A high grade form of mucoepidermoid cancer might occur in the breast as it does in the salivary gland. All high-grade variant cases published had demonstrable lymph node or distant metastases and rapidly fatal outcomes. This report describes a case of high-grade mucoepidermoid carcinoma of the breast with a disease-free interval of 5 years, despite of unfavourable histologic features at the time of diagnosis.
Abstract: Eighty-five women, 18 to 80 years of age, with palpable breast lumps were studied 1-4 days before surgery in order to evaluate 99mTc Tetrofosmin imaging for the detection of malignant breast tumours. Intravenous injection of 99mTc Tetrofosmin was followed by 3 min planar images at 5-60 min postinjection. In the latter 57 patients, planar imaging was preceded by a dynamic study of 20x5 sec images. The myocardium was always included in the field of the left breast. Count rates in suspicious areas were compared with normal tissue areas in the same and the opposite breast and with myocardial counts. Data analysis showed that 77 of the 85 scan results were in agreement with the histological findings; six scans were false negative and two false positive for malignancy. The sensitivity of the method was 90.32% and the specificity 91.30%, with a positive predictive value of 96.55%. We conclude that breast scanning with 99mTc Tetrofosmin may play an important role in the detection of breast malignancies.
Abstract: Fine needle aspiration (FNA) breast smears from 81 male patients have been examined in our laboratory between 1988 and 1994. The cytological criteria for diagnosing male breast lesions and the expression of nuclear organizer regions were evaluated. Of the 81 cases examined cytologically, 50 cases were proven cytologically and histologically to be inactive gynaecomastia, two cases showed florid gynaecomastia and there were 10 adenocarcinomas; in the 17 cases in which no cytological evidence of gynaecomastia or malignancy was found, the histological diagnosis was gynaecomastia in 13 and there was one case of mastopathy; in two cases suspicious of malignancy on cytology the histological examination proved to be florid gynaecomastia in one case and the other showed an adenocarcinoma. The absolute specificity of FNA in this study was 74.28%, the complete specificity 98.5%, the absolute sensitivity 90.9% and the complete sensitivity 100%. The overall accuracy was 97.5%, the positive predictive value 91.66% and the negative predictive value 98.5%. In all cases of male breast carcinoma, AgNOR mean value was > or = 3; thus, it appears that AgNOR mean value 3 could be used as a cut-off value between benign and malignant male breast lesions. Our experience suggests that FNA is an acceptable procedure for the investigation of male breast lesions.
Abstract: The DNA content of ductal breast carcinomas of varying histological grade was measured using static image cytometry and correlated with pS2 expression in the tumour cells. Our study was performed on imprint of surgical biopsies of 60 women with ductal breast cancer. A statistically significant difference was observed between pS2+ expression and grade of malignancy (P < 0.001). The percentage of euploid tumours significantly decreased from grade I to grade II to grade III (P = 0.01). The percentage of aneuploid tumours increased from pS2+ to pS2- breast tumours (P < 0.001). These findings may be indicative of pS2 and DNA ploidy alterations and tumour aggressiveness.
Abstract: The DNA content of 85 ductal breast cancers of different histological grades was evaluated using static cytometry and correlated with immunocytochemical expression of p53 protein in tumour cells in cytological material. A statistically significant difference was observed between p53 protein expression and grade of malignancy (P < 0.001). The percentage of euploid tumours significantly decreased from grade I through grade II to grade III tumours (P < 0.001). Clonal DNA heterogeneity was observed in 26.6% of cases analysed and was correlated with p53 protein expression (P < 0.001). These changes probably reflect genomic alterations which may affect potential malignancy of breast cancer.
Abstract: OBJECTIVE: To investigate the potential of the learning vector quantization (LVQ) neural network for the discrimination of benign from malignant breast lesions. STUDY DESIGN: Using a custom image analysis system on Giemsa-stained smears, 25 parameters describing the size, shape and texture of the cell nucleus were measured. Three thousand nuclei from a total of 9,356 were selected as a training set for the neural network, and the whole data set was used for testing. An additional 238 cells from 16 cases without final cytologic diagnoses were evaluated by the system. The total number of cells (9,594) was collected from 100 patients (68 carcinomas and 32 benign lesions). RESULTS: Cytologic examination of the cases gave two false positive and two false negative results. However, in eight cases of ductal breast carcinoma and in eight cases of benign lesions, histologic confirmation was necessary in order to confirm the cytologic diagnosis. Application of the LVQ permitted correct classification of 87.41% of the cells. Classification at the patient level by using a hypothesis test for proportion with a hypothesis value equal to 50% permitted the correct diagnosis in 98% of patients. CONCLUSION: These results indicate that the use of neural networks combined with image morphometry and statistical techniques may offer useful information about the potential for malignancy, improving the diagnostic accuracy of fine needle aspiration of breast lesions.
Abstract: OBJECTIVE: To investigate pS2 protein expression and estrogen (ER) and progesterone receptor (PR) status of imprints from surgical biopsies of breast cancer cases in relation to the histologic grade of malignancy. STUDY DESIGN: The study group consisted of 50 cases of primary breast carcinomas. For the demonstration of pS2 protein expression an immunocyto-chemical avidin-biotin complex technique was applied. Monoclonal antibody pS2 was used as the primary antibody, diaminobenzidine as the chromogene and hematoxylin as the counterstain. For the evaluation of ERs and PRs, a biochemical method was applied. RESULTS: Sixty-two percent of breast cancer cases showed positive expression of pS2. Of the 31 pS2+ cases, 74% had positive ERs and PRs. A statistically significant difference was observed between pS2 protein expression, ER+, PR+ and histologic grade of malignancy (P < .001). CONCLUSION: Two groups of breast cancer cases can be distinguished: one group that is ER+, PR+ and pS2+, with low malignancy potential, and another group that is ER-, PR- and pS2-, with high malignancy potential.
Abstract: A rare case of metachronous bilateral Paget's disease of the nipple is presented. The occasional failure of routine follow-up to detect certain tumours until biologically advanced and the value of patient observations are mentioned.
Abstract: In 42 postmenopausal women with breast cancer aged 48-85 (mean age 62.4) years, the blood sex hormone levels were measured before and after 6 months of tamoxifen administration (20 mg daily). Follicle-stimulating hormone and luteinizing hormone levels decreased after tamoxifen administration (p < 0.001), but remained in the postmenopausal range, oestradiol levels increased (p < 0.05), sex hormone binding globulin levels increased (p < 0.001), testosterone levels remained stable (p > 0.1), free testosterone levels decreased (p < 0.001), delta4-androstenedione, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate levels remained unchanged (p > 0.1), and basal prolactin levels and their response to thyrotrophin-releasing hormone injection decreased significantly (p < 0.001) after tamoxifen therapy. It is concluded that tamoxifen has many and diverse effects on sex hormone levels, and its adverse effects do not affect the biological status of the patient, except perhaps for oestradiol, that increases in some cases, whose possible effect must be studied.
Abstract: Between January 1984 and December 1990, 56 patients with hydatid liver disease were treated surgically at our Department. Diagnosis was made by using clinical criteria, serology and imaging techniques. Most frequent clinical symptom was abdominal pain or local discomfort (38 patients, 68%). Plain X-ray of the abdomen was helpful in 20 patients (36%), liver ultrasound in 53 (93%) and computerised tumorgraphy in 56 patients, (100%). The immunoelectrophoresis test of "arc 5" was sensitive in 51 patients (91%). Thirty patients (53%) underwent partial resection and omentoplasty, 17 patients (30%) underwent external drainage, two cystic resection (3%), one left lateral lobectomy (2%) and six (11%) underwent omentoplasty and T-tube insertion. Fatal complications did not occur. Four patients developed hepatic abscess (7%), three wound infection (5%), one bowel obstruction (2%) and in five instances (8%) drainage was maintained for more than three months. Of the 49 patients available for follow-up (87%), three (6%) developed recurrent disease.
Abstract: Five patients with necrotizing soft tissue infections of the perineum and scrotum are presented. There were one female and four male patients, aged from 35 to 70 years. Portals of entry were perirectal abscesses in four cases and a scrotal abscess in one case. All patients required extensive surgical debridement and intravenous broad-spectrum antibiotics. Operative debridement involved the scrotum, the perineal and inguinal area, the upper thighs and the anterior abdominal wall. One patient required transverse loop colostomy and one loop sigmoidostomy. One patient was reoperated on after inadequate drainage of a perirectal abscess. Three patients were referred to our unit after some delay, while one patient did not seek medical care until after being febrile for 2 weeks. Despite aggressive debridement, this last patient died of fulminant sepsis. Fournier's gangrene, which is not so rare as in generally considered, is still associated with a high mortality, which can be reduced only by improving medical awareness and early treatment both of the primary cause and of necrotizing fasciitis.
Abstract: Endometriosis of a surgical scar is rare and occurs mainly when a hysterectomy has been performed in the past. Development of malignancy in such a lesion is very unusual. A rare case of primary endometrioid carcinoma in the endometriosis of a caesarean scar is described.
Abstract: The DNA content of 50 breast cancers of varying tumour type, grade and stage was measured using static image cytometry, and correlated with vimentin expression in the tumour cells. A tendency to increased vimentin expression and aneuploidy was observed in high grade and late stage tumours. A statistically significant difference was observed in DNA index and ploidy balance between grade 1 and grades 2 and 3 carcinomas (P < 0.05) and between grade I and stage II carcinomas (P < 0.05). There was a significant difference in the expression of vimentin between grades 1, 2, 3 (P < 0.001), and stages I, II, and III ductal carcinomas (P < 0.05). No significant difference was observed in the proliferation index and the degree of hyperploidy (P > 0.05) Clonal heterogeneity was observed in 25% of breast carcinomas, and was associated with increased vimentin expression. These changes may be indicative of genomic alteration and tumour aggressiveness.
Abstract: Cytologic specimens (FNA) from 42 primary invasive ductal breast carcinomas and 22 matched specimens of cancer tissue were tested for EGFR status, PCNA index and vimentin expression by immunocytochemical staining, using an Extravidin-Biotin method, and their relationship with various prognostic factors was investigated. EGFR positivity, high PC10 score and vimentin positivity were significantly correlated with high histologic grade. The coordinate expression of EGFR, PCNA and vimentin was significantly associated with ER-negative breast carcinomas. A positive trend was observed between high proliferating tumours and EGFR expression. EGFR status and PCNA index were not correlated with axillary lymph node involvement, tumour size, age and menopausal status. Vimentin was preferentially expressed in tumours, with lymph node metastases. Co-expression of EGFR, PCNA and vimentin was determined in most cases. These data suggest that EGFR status, PCNA index and vimentin expression may be important for the prediction of biologically aggressive tumours.
Abstract: Hamartomas of the breast are rare tumor-like lesions composed of ducts, lobules, fat, and fibrous tissue. The clinical and pathologic findings of six cases of patients ranging in age from 19 to 63 years are reported. Diagnosis is difficult, and we emphasize that fine needle aspiration and cytology of the smears is not diagnostic for hamartomas.
Abstract: Seventy-eight confirmed cases of second primary breast cancer in the contralateral breast were encountered over a 22-year period in 1332 women with invasive breast cancer treated in our department. Tumors were grouped into those simultaneously detected in both breasts or within 6 months of each other (synchronous, 1.6%) and those detected within more than 6 months (metachronous, 4.2%). The mean interval between metachronous cancers was 117 months. Patients with bilateral tumors were more likely to have a family history of breast cancer than those with unilateral disease. Women with metachronous tumors tended to be younger when diagnosed with the first carcinoma as compared with those having unilateral or synchronous bilateral cancers. No differences were noticed in size and lymph node status between the first or second tumor of bilateral cases in comparison to patients with unilateral disease. Significantly more (P < 0.05) first metachronous tumors were found to be lobular invasive cancers. Histopathologic type of the first tumor was the same as the second in 62.8 per cent of all cases. Concordance of estrogen receptor status between bilateral tumors was 71.4 per cent. Our results indicate that the risk of developing, a contralateral breast cancer is related to the patient's age, family history of breast cancer, and lobular histology of the tumor.
Abstract: Radioimmunoassays specific for the N and C termini of human prothymosin alpha and the N terminus of human parathymosin alpha were employed for the measurement of the levels of alpha-thymosins in human thymus, spleen, and liver during normal growth and intestine and breast in malignant growth. A differential expression of the two alpha-thymosins was observed in thymus (prothymosin alpha-rich) and liver (parathymosin alpha-rich). A decline in the levels of both alpha-thymosins was found with age, with prothymosin alpha in thymus showing the sharpest change (15- to 30-fold). The levels of both alpha-thymosins were higher in malignant tissues as compared with healthy ones. In breast cancer, in particular, the mean increase for prothymosin alpha and parathymosin alpha was 17.9- and 11.5-fold, respectively. The major crossreactive material was characterized in all cases as intact prothymosin alpha and parathymosin alpha. These results suggest an in vivo relationship of the expression of alpha-thymosins with the human tissue cell proliferation activity.
Abstract: The records of 121 patients with obstructing cancer of the colon were reviewed. About one-third of the patients had metastatic disease at the time of operation. Primary resection and anastomosis of the intestine was performed for most cancers of the ascending or transverse colon. Hartmann's procedure was performed in most patients with cancer of the sigmoid colon and rectum. Wound infection occurred in 20 patients (16.5%) and anastomotic leakage in six (4.9%). The operative mortality rate was 14.9%. The 5-year survival rate was 13.5%. Acute colonic obstruction is associated with high morbidity and mortality. The high incidence of advanced disease, advanced age, delay in tumour excision and unprepared bowel are some of the factors resulting in the poor prognosis of these patients.
Abstract: A patient with Paget's disease of the nipple is reported. The case is of interest in that Paget's disease occurred 21 months after presentation of an infiltrating cancer in the same breast which was treated by conservative surgery reserving the nipple and thus the opportunity for Paget's disease to occur.
Abstract: 116 patients aged 70 or over who were judged to have surgically resectable cancer of the breast were prospectively randomised to tamoxifen 20 mg daily or surgical resection. At a median follow-up of three years, local relapse or progression was seen in 15 (25%) of 60 patients in the tamoxifen group and 21 (37.5%) of 56 in the surgical arm. Distant metastases occurred in 8 (13%) in the tamoxifen group and in 10 (18%) in the surgical arm. There were 13 deaths in the tamoxifen group and 11 in the surgical arm, of which 8 and 9, respectively, were attributable to breast cancer. Disease-free survival did not differ between the groups.
Abstract: To examine the presence and distribution of oestrogen receptors in the normal breast during the menstrual cycle cytological samples obtained by fine needle aspiration from 69 premenopausal women with normal breasts were analysed immunocytochemically with a monoclonal antibody to oestrogen receptor; samples from 15 postmenopausal women were also analysed. The receptor content of breast cancers from 83 premenopausal women was also determined in relation to when during the menstrual cycle excision was performed. In the normal premenopausal women oestrogen receptors were detected in the nuclei of epithelial cells in 21 out 68 (31%) assessable samples. All 21 of these samples were obtained from the 35 women who were studied during the first half of their menstrual cycle (days 28 to 14). None of the 33 samples obtained during the second half of the cycle contained oestrogen receptors. Samples were assessable in eight of the postmenopausal women, six giving a positive result for oestrogen receptor. Fifty one of the 83 carcinomas were positive for oestrogen receptor, 24 having been excised during the first half of the cycle and 27 during the second half. Production of oestrogen receptor protein is suppressed at the time of ovulation in the normal breast epithelium of premenopausal women. In contrast, breast carcinoma cells either synthesise this protein continuously throughout the cycle or fail to express it despite fluctuations of serum hormone concentrations.
Abstract: Nine cases of medullary carcinoma of the thyroid gland (MTC) are reported. Four of the carcinomas were of the familial type. Five of the patients were men and four were women. Patient age ranged from 23 to 66 years, with a mean age of 40 years. The median age of the four patients with the familial MTC was 32 years. A total or a subtotal thyroidectomy was performed in four and five patients, respectively, associated with a modified neck dissection in six patients with involved cervical lymph nodules. An underlying pheochromocytoma of the left adrenal was excised in one patient prior to thyroidectomy. In all cases the parathyroid glands were identified, and in two cases of familial MTC, in which they were grossly enlarged, the parathyroid glands were removed. Four patients died as a result of their disease within 3 years, whereas patients are well 4 to 12 years after surgery. The best chance of cure lies in early diagnosis and an aggressive surgical removal of the primary tumor and any cervical metastases.
