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ABSTRACT: Abstract Background: The aim of this prospective controlled study was to assess the efficacy of two different combination treatment modalities of lymphedema (LE). Manual lymphatic drainage (MLD) and compression bandage combination (complex decongestive therapy) have been compared with intermittent pneumatic compression (IPC) plus self-lymphatic drainage (SLD). Methods and Results: Both MLD with compression bandage (complex decongestive therapy) group (Group I, n=15) and IPC with SLD group (Group II, n=15) received treatment for LE 3 days in a week and every other day for 6 weeks. Arm circumferences were measured before and the 1st, 3rd, and 6th weeks of the treatment. EORTC-QLQ and ASES-tests were performed to assess the quality of life before and after 6 week-treatment. Patients in both groups had similar demographic and clinical characteristics. Even though both treatment modalities resulted in significant decrease in the total arm volume (12.2% decrease in Group II and 14.9% decrease in Group I) (p<0.001), no significant difference (p=0.582) was found between those two groups. Similarly, ASES scores were significantly (p=0.001) improved in both Group I and II without any significant difference between the groups. While emotional functioning, fatigue, and pain scores were significantly improved in both groups, global health status, functional and cognitive functioning scores appeared to be improved only in patients of group I. Conclusions: Different treatment modalities consisting of MLD and compression bandage(complex decongestive therapy) or IPC and SLD appear to be effective in the treatment of LE with similar therapeutic efficacy in patients with breast cancer. However, combination modalities including IPC and SLD may be the preferred choices for their applicability at home.
Lymphatic Research and Biology 09/2012; 10(3):129-35.
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ABSTRACT: Breast cancers in Turkey tend to be diagnosed at advanced stages due to lack of organized comprehensive mammographic screening. In this study, factors associated with having a mammogram among healthy women of screening age in Bahcesehir county, a region in Istanbul, were investigated to assess the feasibility of organized breast cancer screening in Turkey. In this cross-sectional study, 659 healthy women aged between 40 and 69 years were surveyed. A multiple-choice questionnaire was used to obtain information regarding patient demographics, family history of cancer, and patient knowledge on mammographic screening. Factors associated with increased likelihood of having a mammogram included age older than 50 (OR=1.75; 95% CI=1.23-2.49), higher educational level (high school or university graduate; OR=1.55; 95% CI=1.07-2.25), and undergoing periodic gynecologic examinations (OR=5.53; 95% CI= 3.88-7.89). Women aged between 40 and 49 years, who were most likely to have a mammogram within the last 2 years were characterized by a higher educational level (OR=1.94; 95% CI=1.14-3.31), periodic gynecologic examinations (OR=4.06; 95% CI=2.53-6.51), and a first or second degree family history of breast cancer (OR=2.2; 95% CI= 1.06-4.50). In contrast, women aged between 50 and 69 years were more likely to have undergone mammography within the previous 2 years if they also had undergone periodic gynecologic examinations (OR=8.63; 5.04-14.77). Our findings suggest that women of lower educational level and those who do not undergo routine wellness visits with their gynecologist will need to be specifically targeted for educational outreach to achieve broad screening compliance within the population.
The Breast Journal 03/2011; 17(3):260-7. · 1.64 Impact Factor
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Vahit Ozmen,
Beyza Ozcinar,
Hasan Karanlik, Neslihan Cabioglu,
Mustafa Tukenmez,
Rian Disci,
Tolga Ozmen,
Abdullah Igci,
Mahmut Muslumanoglu,
Mustafa Kecer,
Atilla Soran
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ABSTRACT: Breast cancer has been increased in developing countries, but there are limited data for breast cancer risk factors in these countries. To clarify the risk for breast cancer among the Turkish women, an university hospital based nested case-control study was conducted.
Between January 2000 and December 2006, a survey was prospectively conducted among women admitted to clinics of Istanbul Medical Faculty for examination and/or treatment by using a questionnaire. Therefore, characteristics of patients diagnosed with breast cancer (n = 1492) were compared with control cases (n = 2167) admitted to hospital for non-neoplastic, non-hormone related diseases.
Breast cancer risk was found to be increased in women with age (> or = 50) [95% confidence interval (CI) 2.42-3.18], induced abortion (95% CI 1.13-1.53), age at first birth (> or = 35) (95% CI 1.62-5.77), body mass index (BMI > or = 25) (95% CI 1.27-1.68), and a positive family history (95% CI 1.11-1.92). However, decreased breast cancer risk was associated with the duration of education (> or = 13 years) (95% CI 0.62-0.81), presence of spontaneous abortion (95% CI 0.60-0.85), smoking (95% CI 0.61-0.85), breast feeding (95% CI 0.11-0.27), nulliparity (95% CI 0.92-0.98), hormone replacement therapy (HRT) (95% CI 0.26-0.47), and oral contraceptive use (95% CI 0.50-0.69). On multivariable logistic regression analysis, age (> or = 50) years (OR 2.61, 95% CI 2.20-3.11), induced abortion (OR 1.66, 95% CI 1.38-1.99), and oral contraceptive use (OR 0.60, 95% CI 0.48-0.74) were found to be associated with breast cancer risk as statistically significant independent factors.
These findings suggest that age and induced abortion were found to be significantly associated with increased breast cancer risk whereas oral contraceptive use was observed to be associated with decreased breast cancer risk among Turkish women in Istanbul.
World Journal of Surgical Oncology 05/2009; 7:37. · 1.12 Impact Factor
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ABSTRACT: Multifocal and multicentric (MF/MC) breast cancers have been reported to be associated with increased lymph node metastases. The limited data on this issue prompted us to investigate the pathologic and clinical differences between unifocal and MF/MC breast cancer.
Between 1990 and 2002, 1,322 patients with operable invasive breast cancer underwent a definitive operation at our Breast Clinic. Patients with MF/MC breast cancer (n=147, 11%) were compared with patients with unifocal breast cancer (n=1,175; 89%) in terms of pathologic and clinical characteristics.
Patients with MF/MC were found to have a higher frequency of lymph node metastases when the largest diameter was used as a tumor size estimate for MF/MC cancer (unifocal T1 and T2, 35% and 49%, respectively, versus MF/MC T1 and T2, 48% and 67%, respectively; p=0.05 and p=0.003, respectively). When the combined diameter assessment was used, the frequency of lymph node positivity was similarly higher in MF/MC patients versus unifocal patients (unifocal T1 and T2, 35% and 49%, respectively, versus MF/MC T1 and T2, 49% and 61%, respectively; p=0.08 and p=0.046, respectively). At a median followup of 55 months (range 12 to 153 months), 5-year disease-free survival (DFS; unifocal, 88% versus MF/MC, 82%, p=0.14) and overall survival (OS) rates (unifocal, 92% versus MF/MC, 93%, p=0.43) did not show any significant difference between two groups.
Our data suggest that breast tumors with multiple foci have a different biology, with an increased metastatic potential to axillary lymph nodes, regardless of tumor size, that reflects an advanced stage. The clinical relevance of the currently used TNM classification system, which uses the diameter of the largest nodule, is supported by our findings.
Journal of the American College of Surgeons 02/2009; 208(1):67-74. · 4.55 Impact Factor
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Neslihan Cabioglu,
Kelly K Hunt,
Aysegul A Sahin,
Henry M Kuerer,
Gildy V Babiera,
S Eva Singletary,
Gary J Whitman,
Merrick I Ross,
Frederick C Ames,
Barry W Feig,
Thomas A Buchholz,
Funda Meric-Bernstam
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ABSTRACT: Positive/close margins are associated with higher in-breast failure rates after breast-conserving surgery (BCS). We investigated whether intraoperative margin assessment aids in obtaining negative margins, and to evaluate the local control thus achieved.
Between 1994 and 1996, 264 patients underwent BCS for stages 0-III breast cancer [invasive, n = 200; ductal carcinoma in situ (DCIS), n = 64]. Intraoperative margin assessment included gross tissue inspection, specimen radiography, with or without frozen section.
Ninety-two patients (46%) with invasive cancer and 24 (38%) with DCIS had positive/close margins on the permanent section analysis of their initial surgical specimens. Fifty-eight patients (29%) with invasive cancer and six (9%) with DCIS had initial positive/close margins, and were rendered margin-negative by intraoperative analysis and immediate re-excision. Final margins on permanent pathology were positive/close in 52 patients (20%): 34 patients (17%) with invasive cancer and 18 patients (28%) with DCIS. By multivariate analysis, excisional biopsy for diagnosis, larger tumor size, and multifocality were associated with final positive/close margins. Of these 52 patients, 23 underwent a second operation to achieve widely negative margins (13 completion mastectomies, 10 re-excisions). The 5-year ipsilateral breast recurrence-free survival rates after BCS and radiation were 99% for invasive cancer (n = 167) and 100% for DCIS (n = 27).
Intraoperative assessment of margins assisted in identifying positive/close margins and allowed over a quarter of the patients to be rendered margin-negative with intraoperative re-excision at their original operation. This approach resulted in excellent local control in patients treated with BCS and radiation.
Annals of Surgical Oncology 05/2007; 14(4):1458-71. · 4.17 Impact Factor
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ABSTRACT: The aim of the present study was to determine the prognostic relevance of thymidine labeling index (TLI) in patients with breast cancer.
TLI of the primary tumor was measured in 268 patients at the time of the surgical biopsy by an in vitro method.
Fifty-four patients had stage I disease, and 138 patients had stage II disease, and 76 patients had stage III disease. One hundred-four patients were found to have low TLI-index (<3%), and 164 patients had high TLI-index (>/=3%). The median follow-up was 71.5 months (range, 6-138 months). The 5-year overall survival (OS) and disease free survival (DFS) rates was 84% and 74%, respectively. Lymph node involvement, tumor size more than 2 cm, high nuclear grade and estrogen receptor negativity were found to be associated with poorer DFS and OS rates. On subgroup analysis, however, the 5-year OS rate was significantly higher in the low TLI-group than in the high TLI-group in patients with stage I disease (100% vs 76%, p = 0.05).
Our findings suggest that the prognostic significance of TLI appears to be limited to early breast cancer that might help to distinguish patients who need more aggressive adjuvant treatment.
World Journal of Surgical Oncology 01/2007; 5:93. · 1.12 Impact Factor
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ABSTRACT: The prognosis of Fournier's gangrene (FG) depends on early diagnosis and management. In this study, our objective was to identify the distinct features of FG that may influence the clinical outcome.
A retrospective chart review was performed in patients with a diagnosis of FG between January 1999 and December 2003. Etiological and predisposing factors, causative microbiological organisms, and clinical outcome were investigated.
Twenty-five men (71%) and 10 women (29%) were included in the study. Mean age was 59.7 +/- 10.7 (range: 43-88) years. As a predisposing factor, diabetes mellitus (DM) was found to be in 46% of patients. All patients were treated by immediate debridement and wide-spectrum antibiotics. More than one bacterium was found in 75% of the patients' tissue cultures, and most frequently E. coli (43%) was identified. Although there were no etiological factors in 25 patients (71%), various etiological factors were found in 10 patients (29%). Multiple debridements were performed in the majority of the cases. The overall mortality rate was 40%. The mortality rates were found to be relatively higher in patients with diabetes mellitus (DM; 50%), with delayed admission to the hospital (45%), and in patients presenting with sepsis at the first admission to the hospital (78%) compared with others. In the logistic regression model, the presence of sepsis was as the only significant independent risk factor for mortality in FG.
Despite the use of contemporary effective antibiotic treatment, aggressive debridements, and state-of-the-art intensive care conditions, FG still has high mortality and morbidity rates. In our series mortality rates were found to be higher in patients with delayed admission to the hospital, those with DM, and those who initially presented with sepsis.
World Journal of Surgery 10/2006; 30(9):1750-4. · 2.36 Impact Factor
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ABSTRACT: ObjectiveThe prognosis of Fournier’s gangrene (FG) depends on early diagnosis and management. In this study, our objective was to identify
the distinct features of FG that may influence the clinical outcome.
MethodsA retrospective chart review was performed in patients with a diagnosis of FG between January 1999 and December 2003. Etiological
and predisposing factors, causative microbiological organisms, and clinical outcome were investigated.
ResultsTwenty-five men (71%) and 10 women (29%) were included in the study. Mean age was 59.7 ± 10.7 (range: 43–88) years. As a predisposing factor, diabetes mellitus (DM) was found to be in 46% of patients. All patients were treated
by immediate debridement and wide-spectrum antibiotics. More than one bacterium was found in 75% of the patients’ tissue cultures,
and most frequently E. coli (43%) was identified. Although there were no etiological factors in 25 patients (71%), various etiological factors were found
in 10 patients (29%). Multiple debridements were performed in the majority of the cases. The overall mortality rate was 40%.
The mortality rates were found to be relatively higher in patients with diabetes mellitus (DM; 50%), with delayed admission
to the hospital (45%), and in patients presenting with sepsis at the first admission to the hospital (78%) compared with others.
In the logistic regression model, the presence of sepsis was as the only significant independent risk factor for mortality
in FG.
ConclusionsDespite the use of contemporary effective antibiotic treatment, aggressive debridements, and state-of-the-art intensive care
conditions, FG still has high mortality and morbidity rates. In our series mortality rates were found to be higher in patients
with delayed admission to the hospital, those with DM, and those who initially presented with sepsis.
World Journal of Surgery 08/2006; 30(9):1750-1754. · 2.36 Impact Factor
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ABSTRACT: Experimental evidence suggests that CXCR4, a Gi protein-coupled receptor for the ligand CXCL12/stromal cell-derived factor-1alpha (SDF-1alpha), plays a role in breast cancer metastasis. Transactivation of HER2-neu by G protein-coupled receptor activation has been reported as a ligand-independent mechanism of activating tyrosine kinase receptors. We found that SDF-1alpha transactivated HER2-neu in the breast cancer cell lines MDA-MB-361 and SKBR3, which express both CXCR4 and HER2-neu. AMD3100, a CXCR4 inhibitor, PKI 166, an epidermal growth factor receptor/HER2-neu tyrosine kinase inhibitor, and PP2, a Src kinase inhibitor, each blocked SDF-1alpha-induced HER2-neu phosphorylation. Blocking Src kinase, with PP2 or using a kinase-inactive Src construct, and inhibiting epidermal growth factor receptor/HER2-neu signaling with PKI 166 each inhibited SDF-1alpha-stimulated cell migration. We report a novel mechanism of HER2-neu transactivation through SDF-1alpha stimulation of CXCR4 that involves Src kinase activation.
Cancer Research 09/2005; 65(15):6493-7. · 7.86 Impact Factor
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ABSTRACT: The chemokine receptors CCR7 and CXCR4 have been shown to play an important role in cancer metastasis. We therefore studied the differential expression of CCR7 and CXCR4, along with that of the biomarker HER2-neu, to evaluate whether these biomarkers could predict axillary lymph node metastasis in breast cancer.
Biomarker expression levels were evaluated using paraffin-embedded tissue sections of lymph node-negative (n = 99) and lymph node-positive (n = 98) T1 breast cancer by immunohistochemical staining.
Lymph node-positive tumors showed higher rates of high cytoplasmic CCR7 staining (21.5% versus 8.5%, P = 0.013) and HER2-neu overexpression (21.5% versus 9.3%, P = 0.019) than did lymph node-negative tumors. Similarly, high cytoplasmic CXCR4 expression occurred more commonly in lymph node-positive tumors (11.2% versus 5.1%, P = 0.113). In contrast, predominantly nuclear CXCR4 staining was more likely to be found in lymph node-negative tumors (54.5% versus 37.8%, P = 0.018). Furthermore, cytoplasmic CXCR4 coexpressed with HER2-neu was the only factor associated with involvement of four or more lymph nodes (16.7% versus 1.2%, P = 0.04) among lymph node-positive tumors. When all three biomarkers (CCR7, CXCR4, HER2-neu) were utilized together, 50.0% of lymph node-positive tumors highly expressed one of these biomarkers compared with 18.8% of the lymph node-negative tumors (P < 0.0001).
Our results suggest that the chemokine receptor CCR7 is a novel biomarker that can predict lymph node metastases in breast cancer. Utilization of additional markers, such as CXCR4 and HER2-neu, further improves the prediction of the presence and extent of lymph node involvement.
Clinical Cancer Research 08/2005; 11(16):5686-93. · 7.74 Impact Factor
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ABSTRACT: The risk of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is associated with treatment and tumor-related variables, such as surgical margin status and the use of systemic therapy, and these variables have changed over time. Correspondingly, the authors of the current study hypothesized that the contemporary multidisciplinary management of breast carcinoma would lead to an improvement in IBTR rates after BCT.
Between 1970 and 1996, 1355 patients with pathologic Stage I-II invasive breast carcinoma underwent BCT (breast-conserving surgery and adjuvant radiation therapy) at The University of Texas M. D. Anderson Cancer Center. Contemporary methods of analyzing surgical margins were in routine use by 1994. To analyze the effect of this variable and others, patient and tumor characteristics and IBTR rates in patients treated during 1994-1996 were compared with those in patients treated from 1970 to 1993.
Characteristics were similar in patients treated during 1994-1996 (n = 381) and those treated before 1994 (n = 974) except for patients aged >50 years (63.3% vs. 51.7%, P < 0.001), and patients who had a family history of breast carcinoma (37.9% vs. 30.8%, P = 0.017). Patients treated after 1994 were less likely to have positive or unknown margins (2.9 % vs. 24.1 %, P = 0.0001), more likely to receive chemotherapy (40.5% vs. 26%, P < 0.001), and more likely to receive hormonal therapy (33.3% vs. 19.4%, P < 0.001), but less likely to receive radiation boosts to the primary tumor bed (59.8% vs. 89%, P < 0.001). The 5-year cumulative IBTR rate was significantly lower among patients treated in 1994-1996 than among patients treated before 1994 (1.3% vs. 5.7%, P = 0.001) largely because of the drop in IBTR rates among patients aged < or = 50 years (1.4 % vs. 9.1 %, P = 0.0001). On multivariate analysis, age > 50 (hazards ratio [HR] = 0.401; P = 0.0001), presence of negative surgical margins (HR = 0.574; P = 0.017), and use of adjuvant hormonal therapy (HR = 0.402; P = 0.05) were independent predictors of improved 5-year IBTR-free survival. On subgroup analysis, use of chemotherapy was associated with increased IBTR-free survival among women aged < or = 50 years (HR = 0.383; P = 0.001). Although 5-year cumulative IBTR rates were lower among women aged > 50 years than among younger women before 1994 (2.6 % vs. 9.1%, P < 0.0001), no such difference was found in the group treated in 1994-1996 (1.2 % for age > 50 yrs vs. 1.4 % for < or = 50 yrs, P = 0.999).
The IBTR rate after BCT appears to be declining, especially among patients < 50 years of age. However, long-term follow-up is necessary to confirm this finding. This finding may reflect changes in surgical approaches and pathologic evaluation as well as an increased use of systemic therapy. The current low incidence of IBTR with multidisciplinary management of breast carcinoma may result in more patients choosing BCT over mastectomy.
Cancer 07/2005; 104(1):20-9. · 4.77 Impact Factor
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ABSTRACT: The prognosis of necrotizing fasciitis (NF) depends on early diagnosis and management. Idiopathic NF may be more challenging, because it occurs in the absence of a known causative factor. Therefore, our purpose in this study was to identify the distinct features of idiopathic NF that may be important in early recognition of this disease and determine the factors associated with mortality. A retrospective chart review was performed in patients with a diagnosis of NF between 1988 and 2003. Patients were classified as idiopathic and secondary NF, and data were analyzed in terms of etiological and predisposing factors, causative microbiological organisms, and clinical outcome. The study included 98 patients, 63 men and 35 women, with a diagnosis of NF. The median age was 55.5 years (range, 13 - 80). Idiopathic NF occurred in 60 of 98 patients (61%). The principal anatomic sites of infection for NF were perineal localisation in 55 patients (66%) and extremities in 31 patients (32%). Characteristics that distinguish patients with idiopathic NF from secondary NF were as follows: age older than 55 years (P = 0.0001), presence of comorbid illnesses like DM (P = 0.007) or chronic renal failure (P = 0.041), and perineal localization (P = 0.008). By logistic regression analysis, independent risk factors for idiopathic NF remained age > 55 years and perineal localization as statistically significant factors, when all the significant variables found in univariate analysis were included in the model. The majority of patients (82%) had polymicrobial infections. The mortality rate was 35 per cent. All patients were treated with radical surgical debridement and a combination of antibiotics. Female gender, presence of malignant disease, and diabetes mellitus (DM) were found to be associated with increased mortality as independent factors in logistic regression analysis, when all of these three factors were included in the model. Understanding the distinct clinical characteristics and the factors associated with mortality in patients with NF may lead to rapid diagnosis and improve the survival rates. Therefore, idiopathic NF is a crucial entity that requires serious suspicion for its diagnosis.
The American surgeon 05/2005; 71(4):315-20. · 1.28 Impact Factor
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Neslihan Cabioglu,
Aysegul Sahin,
Michele Doucet,
Ekrem Yavuz,
Abdullah Igci,
Engin O Yildirim,
Esin Aktas,
Sema Bilgic,
Bayram Kiran,
Gunnur Deniz,
Janet E Price
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ABSTRACT: Interactions between the CXCR4 chemokine receptor in breast cancer cells and the ligand CXCL12/SDF-1alpha are thought to play an important role in breast cancer metastases. In this pilot study, CXCR4 expression along with other biomarkers including HER2-neu and EGFR, were measured in primary tumor samples of patients with operable breast cancer to test whether any of these biomarkers alone and in combination could indicate breast cancer with high likelihood of metastasizing to bone marrow. Cytokeratin (CK) positive cells in bone marrow were identified by flow-cytometry following enrichment with CK 7/8 antibody-coupled magnetic beads. Primary tumors (n = 18) were stained with specific antibodies for CXCR4, HER2-neu, EGFR, and PCNA using an indirect avidin-biotin horseradish peroxidase method. The majority of the patients had T2/T3 tumors (72%), or lymph node involvement (67%) as pathologic characteristics that were more indicative of high-risk breast cancer. High CXCR4 cytoplasmic expression was found in 7 of 18 patients (39%), whereas 6 of 18 patients (33%) were found to have CK positivity in bone marrow. The median number of CK(+) cells was 236 (range, 20-847) per 5 x 10(4) enriched BM cells. The presence of CK(+) cells in bone marrow was found to be associated with increased expression of CXCR4 alone or in addition to EGFR and/or HER2-neu expression (P = 0.013, P = 0.005, and P = 0.025, respectively) in primary tumors. Furthermore, three patients with high CK positivity (>236 CK(+) per 5 x 10(4) enriched bone marrow cells) in bone marrow exclusively expressed high levels of CXCR4 with EGFR/HER2-neu (P = 0.001). Our data suggest that high CXCR4 expression in breast cancer may be a potential marker in predicting isolated tumor cells in bone marrow. CXCR4 coexpression with EGFR/HER2-neu might further predict a particular subset of patients with high CK positivity in bone marrow.
Clinical and Experimental Metastasis 02/2005; 22(1):39-46. · 3.52 Impact Factor
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Neslihan Cabioglu,
Aysegul Sahin,
Michele Doucet,
Ekrem Yavuz,
Abdullah Igci,
Engin O.Yildirim,
Esin Aktas,
Sema Bilgic,
Bayram Kiran,
Gunnur Deniz,
Janet E. Price
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ABSTRACT: Interactions between the CXCR4 chemokine receptor in breast cancer cells and the ligand CXCL12/SDF-1α are thought to play an important role in breast cancer metastases. In this pilot study, CXCR4 expression along with other biomarkers including HER2-neu and EGFR, were measured in primary tumor samples of patients with operable breast cancer to test whether any of these biomarkers alone and in combination could indicate breast cancer with high likelihood of metastasizing to bone marrow. Cytokeratin (CK) positive cells in bone marrow were identified by flow-cytometry following enrichment with CK 7/8 antibody-coupled magnetic beads. Primary tumors (n = 18) were stained with specific antibodies for CXCR4, HER2-neu, EGFR, and PCNA using an indirect avidin–biotin horseradish peroxidase method. The majority of the patients had T2/T3 tumors (72%), or lymph node involvement (67%) as pathologic characteristics that were more indicative of high-risk breast cancer. High CXCR4 cytoplasmic expression was found in 7 of 18 patients (39%), whereas 6 of 18 patients (33%) were found to have CK positivity in bone marrow. The median number of CK+ cells was 236 (range, 20–847) per 5נ104 enriched BM cells. The presence of CK+ cells in bone marrow was found to be associated with increased expression of CXCR4 alone or in addition to EGFR and/or HER2-neu expression (P = 0.013, P = 0.005, and P = 0.025, respectively) in primary tumors. Furthermore, three patients with high CK positivity (>236 CK+ per 5נ104 enriched bone marrow cells) in bone marrow exclusively expressed high levels of CXCR4 with EGFR/HER2-neu (P = 0.001). Our data suggest that high CXCR4 expression in breast cancer may be a potential marker in predicting isolated tumor cells in bone marrow. CXCR4 coexpression with EGFR/HER2-neu might further predict a particular subset of patients with high CK positivity in bone marrow.
Clinical and Experimental Metastasis 01/2005; 22(1):39-46. · 3.52 Impact Factor
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ABSTRACT: Few studies in the literature address the surgical management of patients with breast carcinoma who present with associated nipple discharge. The purpose of the current study was to determine the feasibility of breast-conserving surgery (BCS) for these patients.
The medical records of patients who presented with pathologic nipple discharge and underwent diagnostic or curative surgery between January 1990 and December 2002 were retrospectively reviewed.
A total of 188 patients presented with nipple discharge during the study period. Of those, 47 had breast carcinoma. One patient had metachronous bilateral nipple discharge associated with malignant disease. Therefore, medical records associated with a total of 48 cases were reviewed. The median patient age was 52 years (range, 29-87 years), and the median follow-up duration was 45 months (range, 6-109 months). Twenty-nine patients had ductal carcinoma in situ (DCIS), 14 had Stage I disease, 3 had Stage II disease, and 2 had Stage III disease. Twenty-four patients were ultimately treated with mastectomy. For 16 of these patients, mastectomy was required because extensive disease was found in reexcisional segmental mastectomy specimens. Among patients with Stage 0 or I disease, the incidence of occult nipple-areola complex (NAC) involvement was 16% (3 of 19 patients). Twenty-four patients were ultimately treated with BCS with (n = 13) or without (n = 11) adjuvant radiotherapy. Local disease recurrence was noted at 14, 28, and 40 months, respectively, in 3 patients who declined adjuvant radiotherapy after BCS for DCIS. Among patients treated with BCS, comedonecrosis, multifocality, and the absence of adjuvant radiotherapy were associated with decreased local recurrence-free survival (P = 0.0005, P = 0.045, and P = 0.013, respectively). However, disease-free survival (mean +/- standard error) was similar for patients who underwent mastectomy and patients who underwent BCS (90 +/- 6 months; 95% confidence interval [CI], 78-101 months vs. 82 +/- 6 months; 95% CI, 69-94 months; P = 0.528). One patient with Stage I disease died of distant metastases at 99 months.
Patients with breast carcinoma accompanied by nipple discharge presented primarily with early-stage breast carcinoma associated with DCIS. Occult NAC involvement was not an uncommon finding in patients with early-stage breast carcinoma. Nonetheless, BCS can be performed safely if negative margins are achieved and if appropriate adjuvant radiotherapy or systemic therapy is administered.
Cancer 09/2004; 101(3):508-17. · 4.77 Impact Factor
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ABSTRACT: The aim of this study is to evaluate the prognostic role of thymidine labeling index in patients with breast cancer. Cellular proliferation rates in 155 breast cancer specimens were investigated by 3H-thymidine labeling index (3H-TLI). Median age was 47 years (range: 23-76). At presentation, 11 patients (7.1%) had stage I disease, 76 (49%) had stage II, 64 (41.3%) had stage III disease, and 4 (2.6%) had metastatic involvement. Patients were placed in 2 groups based on their proliferative indices. The cut-off level was assigned as the median TLI value of the whole group. Correlations between proliferative activity of the tumors based on 3H-TLI levels and various previously established prognostic factors, as well as the influence of proliferative activity on survival as a clinical outcome, were analyzed. The mean and median TLI values for the whole group of patients were 4.36 +/- 4.96% and 2.76% (range: 0-23.6), respectively. There was a significant association of nuclear grade with TLI (P = 0.04). Patients who were alive with no sign of disease at the final follow-up examination had a significantly lower median TLI rate than those who were either alive with disease or those who had eventually died with disease progression (3.7% versus 1.9%, respectively; P = 0.04). Patients with locally advanced disease (N2 + N3 involvement) had a significantly higher median TLI rate than those with local nodal involvement (N1) (3.4% versus 1.7%, respectively, P = 0.026). Furthermore, TLI levels showed a significant association with overall survival in patients with node-negative disease (P = 0.02). Based on the results of this study, it can be concluded that TLI plays a significant prognostic role in a subset of patients with node-negative breast cancer. Furthermore, TLI appears to have a predictive value for the clinical outcome of patients with breast cancer. These findings may justify a more aggressive therapeutic approach in patients with high TLI levels. Further large-scale, prospective studies are required before a definite conclusion can be reached.reached.
American journal of clinical oncology 09/2004; 27(4):400-6. · 2.21 Impact Factor
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ABSTRACT: Lymphomas secondarily involving the breast are uncommon, although they do represent the largest group of tumors metastatic to breast. A 20-year-old female with lymphoblastic lymphoma (LBL) presented here with 3 month history of weight loss, night sweats, fatigue and a mass in her left breast. Her physical examination revealed a left breast mass, lympadenopathy, bilateral pleural effusion and hepatomegaly. WBC count was 17,710/mm3 and LDH was mildly elevated. Breast ultrasound showed a 1.7 cm mass in the inner lower quadrant of left breast. Biopsy of the breast mass showed diffuse infiltration with small, round atypical cells which did not stain with CD20, CD43, CD34, cytokeratine and were positive for CD3. She was diagnosed as leukemic phase of a precursor T-cell LBL and treated with 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), intrathecal methotrexate and cranial radiotherapy, achieving a complete response. She then was started on maintenance therapy. Four months later she returned with CNS involvement and was started on induction treatment. She had a very aggressive course of disease and died only 12 months after diagnosis. Breast involvement is very rarely seen in precursor T-cell LBL/ALL and in this patient occurred secondarily as part of widespread disease.
Leukemia and Lymphoma 05/2004; 45(4):833-6. · 2.58 Impact Factor
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ABSTRACT: There is no consensus about the use of the various diagnostic tests and surgical procedures available to confirm or rule out breast cancer in patients presenting with nipple discharge. This study was designed to identify patient and nipple-discharge characteristics associated with the diagnosis of breast cancer and to determine the utility of mammography, sonography, ductography, and cytology in surgical decision making in patients presenting with pathologic nipple discharge.
We reviewed the medical records of all patients who presented with nipple discharge at our institution between August 1993 and September 2000. Patient and nipple-discharge characteristics and findings on imaging studies and cytologic examination were analyzed.
A total of 146 patients presented at our institution with nipple discharge during the study period. Of these, 52 had clinically benign discharge and were managed without surgical intervention; 94 patients had pathologic discharge and underwent a biopsy procedure for histologic diagnosis, treatment, or both. Logistic regression analysis identified mammographic (relative risk [RR] = 10.47, 95% confidence interval [CI] 2.36 to 46.39, p = 0.0002) and sonographic (RR = 5.54, 95% CI 1.27 to 25.40, p = 0.028) abnormalities as independent factors associated with a malignant diagnosis. Nineteen cancers, 62 papillomas, and 13 other benign lesions were identified among the patients with pathologic discharge. In 3 patients with cancer (15.8%) and 30 patients with a papilloma (48.4%), ductography was the only means of identifying lesions to be resected. Patients who underwent ductography-guided operation (n = 42, 50%) or any surgical procedure including a localization study (n = 66, 78.6%) were significantly more likely than patients who underwent central duct excision alone to have a specific underlying lesion identified (p = 0.045 and p = 0.033, respectively).
Abnormalities on mammography and sonography in patients with nipple discharge should alert physicians to the possibility of a breast cancer diagnosis. In patients with pathologic discharge with normal findings on physical examination and other imaging studies, ductography might be the only means of localizing and resecting breast lesions associated with nipple discharge.
Journal of the American College of Surgeons 04/2003; 196(3):354-64. · 4.55 Impact Factor
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ABSTRACT: There are few data about the reliability of sentinel node biopsy in patients with multi-focal breast cancer. The aim of this study was to determine the factors affecting the identification and accuracy of the sentinel node, comparing multifocality with other variables, using peritumoral isosulfan blue dye injection technique alone. Between 1998 and 2001, 122 patients with clinically negative nodes from a single institute were eligible for sentinel lymph node biopsies (SLNBs). All patients underwent conventional axillary lymph node dissection (ALND). SLNs were identified in 111 of 122 (91%) cases, and analyzed by hematoxylin and eosin. Twenty-one patients with multifocal breast cancer were determined by clinical or pathologic examination (gross or microscopic). Success in locating the sentinel node was unrelated to patient's age, tumor size, type, location, histological or nuclear grade, multifocality, or a previous surgical biopsy. SLNBs accurately predicted the status of the axilla in 104 of the 111 patients (93.7%), while 18 of the 21 patients with multi-focal breast cancer (85.7%) had successful lymphatic mapping. The false negative (FN) rate was 11.3% among patients with successful SLNBs. Multifocality and tumor size (>2 cm) were associated significantly with decreased accuracy and increased FN rates (for multifocality, p = 0.007 and p = 0.006, and for tumor size >2 cm, p = 0.04 and p = 0.05, respectively) in binary logistic regression analysis, whereas excisional biopsy, tumor location in the upper outer quadrant and patient's age did not significantly affect the accuracy and FN rates in univariate analysis. These results suggest sentinel lymph node biopsy using peritumoral isosulfan blue injection method alone can accurately predict axillary status in patients with clinically negative nodes, but patients with multi-focal disease and large tumor size may not be ideal candidates.
Breast Cancer Research and Treatment 01/2003; 76(3):237-44. · 4.43 Impact Factor
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Neslihan Cabioglu,
Abdullah Igci,
Engin O Yildirim,
Esin Aktas,
Sema Bilgic,
Ekrem Yavuz,
Mahmut Muslumanoglu,
Yavuz Bozfakioglu,
Mustafa Kecer,
Vahit Ozmen,
Gunnur Deniz
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ABSTRACT: An ultrasensitive tumor enriched flow-cytometric assay was used to determine its feasibility in detection of isolated tumor cells (ITC) in bone marrow (BM) of patients with breast cancer.
Epithelial cells were removed by magnetic microbeads conjugated with an anti-cytokeratin 7/8 monoclonal antibody to enrich tumor cells in BM samples. A specific gate for MCF-7 breast cancer cells (gate(MCF-7 cells)) was also taken into consideration in addition to a gate including all enriched BM cells (gate(enriched BM cells)) in flow-cytometric analysis to enhance the specificity of the method.
Nineteen patients with stage I/II were evaluated. Ten patients (53%) were found to have cytokeratin positive (CK(+)) cells according to the gate(enriched BM cells) whereas 6 patients (32%) had CK(+) cells when the gate(MCF-7 cells) was taken into account.
New strategies in nonmorphological ultrasensitive techniques might be useful to categorize patients with ITCs having different tumor morphology and characteristics.
The American Journal of Surgery 12/2002; 184(5):414-7. · 2.78 Impact Factor
