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The TNM staging system for breast cancer, as described by the American Joint Committee on Cancer (AJCC), was introduced to act as a standard tool to assess the prognosis of patients with newly diagnosed breast cancer. In 2009, the seventh revised edition of the TNM system was published to reflect the updates in technology and clinical evidence. Rapid advances in both clinical and laboratory sciences along with translational research have raised questions about the feasibility of ongoing TNM staging to determine whether to apply systemic therapy based on anatomic prognosis. In 2017, the 8th revised edition of the TNM system was published. Clinical and pathological stage tables were incorporated in addition to the traditional anatomical prognostic stage tables. The pathological stage table is based on clinical information, biomarker data, and findings from surgery and resected tissue. It is anticipated that updates will be made on a more frequent basis than the 6- to 8-year cycle of TNM revisions, when relevant validated information is available.

Background: The MF07-01 trial is a multicenter, phase III, randomized, controlled study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone for treatment-naïve stage IV breast cancer (BC) patients. Methods: At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. Results: The trial enrolled 274 patients: 138 in the LRT group and 136 in the ST group. Hazard of death was 34% lower in the LRT group than in the ST group (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.49–0.88; p = 0.005). Unplanned subgroup analyses showed that the risk of death was statistically lower in the LRT group than in the ST group with respect to estrogen receptor (ER)/progesterone receptor (PR)(+) (HR 0.64; 95% CI 0.46–0.91; p = 0.01), human epidermal growth factor 2 (HER2)/neu(–) (HR 0.64; 95% CI 0.45–0.91; p = 0.01), patients younger than 55 years (HR 0.57; 95% CI 0.38–0.86; p = 0.007), and patients with solitary bone-only metastases (HR 0.47; 95% CI 0.23–0.98; p = 0.04). Conclusion: In the current trial, improvement in 36-month survival was not observed with upfront surgery for stage IV breast cancer patients. However, a longer follow-up study (median, 40 months) showed statistically significant improvement in median survival. When locoregional treatment in de novo stage IV BC is discussed with the patient as an option, practitioners must consider age, performance status, comorbidities, tumor type, and metastatic disease burden. © 2018, Society of Surgical Oncology.

Background: Implant-based breast reconstruction after mastectomy has recently been reported to be the preferred type of surgery among breast-specific surgeons and plastic surgeons. Aims: To explore the significant clinicopathological factors associated with long-term outcome related to local recurrences of the nipple among patients who underwent immediate breast reconstruction with tissue expander or implant after mastectomy. Study Design: Retrospective cohort.Methods: From January 2007 to January 2013, 51 breast cancer patients who underwent immediate breast reconstruction with tissue expander or implant were retrospectively analysed. Patients’ demographic data, clinicopathological characteristics, and clinical outcome by disease-free survival and disease-specific survival analyses were determined. Results: The median follow-up was 64 (31-114) months. Of the 57 mastectomies, 41 were skin sparing mastectomy (72%) and 16 were nipple-areola sparing mastectomy (28%). Immediate breast reconstruction surgery included tissue expander (n=46, 81%) or implant (n=11, 19%) placement. The molecular subgroups of 47 invasive cancers were as follows: luminal A (n=23, 49%), luminal B (n=16, 34%), non-luminal HER2 (n=5, 10.6), triple negative breast cancer (n=3, 6.4%). The 5-years disease-specific survival, disease-free survival, and locoregional recurrence-free survival rates were 96.8%, 90%, and 97.6% respectively. Patients with luminal A cancer were found to have an improved 5-year disease-free survival time than other (luminal A; 100% vs. non-luminal A; 78%; p=0.028). Of the 14 nipple-areola sparing mastectomy, 13 had a close median tumour distance to nipple-areola complex (

Objective Male breast cancer (MBC) is a rare type of cancer in the breast cancer series and in the male population. Data is usually extrapolated from female breast cancer (FBC) studies. We aim to study the clinicopathological characteristics and outcome of MBC patients at our institution and we aim to emphasize the differences compared with FBC. Materials and methods Between January 1993 and April 2016, 56 male patients who were diagnosed as breast cancer and underwent surgical operation were retrospectively analyzed. Patients were evaluated for demographical characteristics, surgery type, clinicopathological characteristics, adjuvant and neoadjuvant treatments, follow-up time, overall survival (OS), disease free survival (DFS), and disease specific survival (DSS). Results The ratio of MBC among all breast cancers at our institution is 1%. The median age was 64 (34-85). Surgical procedures were modified radical mastectomy (MRM) in 41 patients (77%), simple mastectomy in 11 patients (21%), and lumpectomy in 1 patient (2%). Two patients were Stage 0 (4%), 7 were Stage 1 (13%), 12 were Stage 2 (22.6%), and 32 were Stage 3 (60.4%). Molecular subtypes of the invasive tumors were luminal A in 40 (80%), luminal B in 6 (12%), HER-2 type in 1 (2%), and basal-like in 3 (6%). Median follow-up time was 77 (3-287) months. 5-year and 10-year OS, DFS, and DSS rates were 80.7%, 96%, 95.6% and 71.6%, 81.9%, 91.7% respectively. Conclusion MBC presents different clinicopathological and prognostic factors when compared to FBC. Our survival rates are higher than the average presented in available literature. Because of the high rate of hormone receptor positivity, hormonal therapy is the mainstay for the treatment of estrogen receptor (ER)+ male breast cancer.

Background The aim of this study is to compare the clinical outcome in T2 breast cancer patients who underwent preoperative chemotherapy (PC) and who did not. The study also tried to define a subgroup of patients, who are more beneficial after PC in terms of lower re-excision rates, better cosmetic results and local recurrence free survival. Materials and methods 251 consecutive patients treated for nonmetastatic T2 invasive breast cancer were analyzed retrospectively. Of those; 141 underwent primary surgery (PS) followed by chemotherapy, whereas 110 were treated with combination of PC and surgery. Results The patients who were treated with PC had a significantly higher incidence of negative margins and lower rate of re-excision (5% vs. 16%, p = 0.02). Of all patients attempted breast conserving surgery (BCS), patients in the PC group were more likely to undergo BCS as their definitive operation compared to patients with PS group (BCS rates; PC group: 99% vs. PS group: 92%, p = 0.05). Multifocal disease (OR: 7, 95% Cl, 2.7–18.4, p = 0.0001) and PC (OR = 0.2; 95% CI, 0.06–0.72, p = 0.01) were factors associated with margin positivity in patients treated with BCS. There was no statistically significant difference in 5 year local-recurrence free survival rates between 2 groups. Conclusions Our study shows that PC significantly decreases the re-excision in patients undergoing BCS with primary T2 breast tumors. This data suggests that any patient with a tumor greater than 2 cm might be considered for PC to increase BCS success with final negative margins.

Appendix vermiformis duplex is an infrequent malformation. However if it is missed out, there might be some complications and medicolegal troubles. A surgeon must be aware of any other appendix during appendectomy. Therefore, the possible locations and shapes described in the Cave-Wallbridge classification should be considered by the surgeon. In this case report, we present a patient with a horseshoe-type dupplication of appendix in a perforated appendicitis diagnosed during an emergency laparotomy.

Objective: We used the results from the first three screening rounds of Bahcesehir Mammography Screening Project (BMSP), a 10-year (20092019) and the first organized population-based screening program implemented in a county of Istanbul, Turkey, to assess the potential cost-effectiveness of a population-based mammography screening program in Turkey. Materials and Methods: Two screening strategies were compared: BMSP (includes three biennial screens for women between 40-69) and Turkish National Breast Cancer Registry Program (TNBCRP) which includes no organized population-based screening. Costs were estimated using direct data from the BMSP project and the reimbursement rates of Turkish Social Security Administration. The life-years saved by BMSP were estimated using the stage distribution observed with BMSP and TNBCRP. Results: A total of 67 women (out of 7234 screened women) were diagnosed with breast cancer in BMSP. The stage distribution for AJCC stages O, I, II, III, IV was 19.4%, 50.8%, 20.9%, 7.5%, 1.5% and 4.9%, 26.6%, 44.9%, 20.8%, 2.8% with BMSP and TNBCRP, respectively. The BMSP program is expected to save 279.46 life years over TNBCRP with an additional cost of $ 677.171, which implies an incremental cost-effectiveness ratio (ICER) of $ 2.423 per saved life year. Since the ICER is smaller than the Gross Demostic Product (GDP) per capita in Turkey ($ 10.515 in 2014), BMSP program is highly cost-effective and remains cost-effective in the sensitivity analysis. Conclusion: Mammography screening may change the stage distribution of breast cancer in Turkey. Furthermore, an organized population-based screening program may be cost-effective in Turkey and in other developing countries. More research is needed to better estimate life-years saved with screening and further validate the findings of our study. Roche Turkey; Breast Health Society of Turkey (MEMEDER); Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Advancing Translational Sciences (NCATS) [UL1TR000427]; NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Advancing Translational Sciences (NCATS) [UL1TR000427] Funding Source: NIH RePORTER The study was funded by Roche Turkey and in part by the Breast Health Society of Turkey (MEMEDER). Also, it was partially supported by the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), grant UL1TR000427. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Background: The Bahcesehir Breast Cancer Screening Project is the first organized population based breast cancer mammographic screening project in Turkey. The objective of this prospective observational study was to demonstrate the feasibility of a screening program in a developing country and to determine the appropriate age (40 or 50 years old) to start with screening in Turkish women. Materials and Methods: Between January 2009 to December 2010, a total of 3,758 women aged 40-69 years were recruited in this prospective study. Screening was conducted biannually, and five rounds were planned. After clinical breast examination (CBE), two-view mammograms were obtained. True positivity, false positivity, positive predictive values (PPV) according to ACR, cancer detection rate, minimal cancer detection rate, axillary node positivity and recall rate were calculated. Breast ultrasound and biopsy were performed in suspicious cases. Results: Breast biopsy was performed in 55 patients, and 18 cancers were detected in the first round. The overall cancer detection rate was 4.8 per 1,000 women. Most of the screened women (54%) and detected cancers (56%) were in women aged 40-49. Ductal carcinoma in situ (DCIS) and stage I cancer and axillary node positivity rates were 22%, 61%, and 16.6%, respectively. The positive predictivity for biopsy was 32.7%, whereas the overall recall rate was 18.4 %. Conclusions: Preliminary results of the study suggest that population based organized screening are feasible and age of onset of mammographic screening should be 40 years in Turkey.

Purpose Bahcesehir Breast Cancer Screening Program is a population based organized screening program in Turkey, where asymptomatic women aged 40-69 years are screened biannually. In this prospective study, we aimed to determine the mammographic findings of screen-detected cancers and discuss the efficacy of breast cancer screening in a developing country. Methods A total of 6912 women were screened in three rounds. The radiologic findings were grouped as mass, focal asymmetry, calcification, and architectural distortion. Masses were classified according to shape, border, and density. Calcifications were grouped according to morphology and distribution. Cancers were grouped according to the clinical stage. Results Seventy cancers were detected with an incidence of 4.8/1000. Two cancers were detected in other centers and three were not visualized mammographically. Mammographic presentations of the remaining 65 cancers were mass (47.7%, n=31), calcification (30.8%, n=20), focal asymmetry (16.9%, n=11), architectural distortion (3.1%, n=2), and skin thickening (1.5%, n=1). The numbers of stage 0, 1, 2, 3, and 4 cancers were 13 (20.0%), 34 (52.3%), 14 (21.5%), 3 (4.6%), and 1 (1.5%), respectively. The numbers of interval and missed cancers were 5 (7.4%) and 7 (10.3%), respectively. Conclusion A high incidence of early breast cancer has been detected. The incidence of missed and interval cancers did not show major differences from western screening trials. We believe that this study will pioneer implementation of efficient population-based mammographic screenings in developing countries.

Background The MF07-01 trial is a multicenter randomized study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone in de novo stage IV breast cancer (BC) patients. The aim of this study is to evaluate the importance of LRT in patients who lived at least 5 years after the diagnosis of de novo Stage IV BC. Methods At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. Continuous and categorical variable differences between LRT and ST groups were analyzed using t-test and Chi-square test, respectively. Overall survival (OS) and 5-year survival rates were compared using Kaplan-Meier log-rank tests. Univariate and multivariate Cox models were used to estimate hazard ratios. Results During 124 months of follow-up, 26% of patients in LRT group and 11% of patients in ST group remained alive. Median survival was 46 months for LRT (n = 134) and 35.5 months for ST (n = 132) [HR:0.65, 95%CI;0.49-0.85, p = 0.002]. Solitary bone metastasis patients’ median survival was 14.5 months longer in the LRT group compared with the ST group [HR:0.53, 95%CI; 0.29-0.98, p = 0.04]; 22% of solitary bone metastasis patients in the LRT group and 5% in the ST group were alive. Regarding the patients who lived at least 5 years since randomization, LRT (p = 0.004), hormone receptor positivity (p = 0.007), hormonotherapy (p = 0.0001), bisphosphonates usage (p = 0.02), T2 tumor (p = 0.0008) and 2 or more organ metastases (p = 0.007) were associated with OS in univariate analysis, and in a multivariate Cox proportional model with a significant baseline and clinical characteristics, LRT [OR = 1.75, p = 0.05)], bisphosphonates usage [OR = 1.93, p = 0.05), T2 tumor [OR = 3.5, p = 0.003), and 2 or more organ metastases [OR = 0.48, p = 0.03] were found to be significantly related with OS. Conclusions In the current analysis, patients at the diagnosis of de novo stage IV BC who underwent LRT followed by ST had a 75% higher chance to live at least 5 years compared with the patients who received only ST. Longer follow-up of the study discloses that LRT should be presented to the patient when discussing treatment options. Clinical trial identification NCT00557986. Legal entity responsible for the study Turkish Federation of Breast Diseases Societies. Funding Turkish Federation of Breast Diseases Societies. Disclosure All authors have declared no conflicts of interest.

Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive and a rare subtype of breast cancer. In this study, we aimed to investigate differences between pure and mixed IMPCs of the breast in terms of clinicopathologic features, and also to analyze the significance of expressions of ARID1A and bcl-2 regarding prognosis. Sixty-nine of IMPCs consisting of 21 pure and 48 mixed type diagnosed at Pathology Department of Istanbul Medical Faculty between 2000 and 2011, who had complete follow-up data, were collected to analyze ARID1A and bcl-2 expressions immunohistochemically with prognosis. The median follow-up period was 94 months. No significant difference was found between pure and mixed type IMPC, as well as in luminal subgroups in terms of prognostic and clinicopatologic features. ARID1A and human epidermal growth factor receptor-2 (Her-2) status were found to be independent prognostic factors of both overall survival (OS) (HR=6.1, 95% CI 1.4-26.6, P=.02; HR=15.9, 95% CI 3.5-71.5, P

For axillary staging, preoperative US and needle biopsy have emerged as effective methods for triaging women with breast cancer directly to axillary surgery for SLNB or ALND or to neoadjuvant chemotherapy in those with axillary node-positive disease. However, there is no perfect modality to identify metastatic disease in breast cancer; every diagnostic test has its own advantages and limitations. The available evidence suggests routine evaluation for stage III and possibly stage II breast cancer using imaging techniques including FDG PET/CT. The workup of abnormal findings in breast cancer patients is by patient signs and symptoms including history and physical examination, laboratory tests, imaging, biopsy of suspicious finding in imaging studies, and monitoring serum markers.

Local recurrence after breast-conservation treatment is most often detected by breast imaging followed by a biopsy for histopathological confirmation. Patients with invasive local recurrence should also undergo a staging workup, mostly by a positron emission tomography-computed tomography (PET-CT), to eliminate the possibility of systemic disease. Although mastectomy is the standard treatment, data are also available regarding a repeat breast-conservation approach with or without reirradiation with accelerated brachytherapy or intraoperative radiotherapy with a potential subsequent increased risk for local recurrence. Local recurrence after mastectomy as a chest wall recurrence (CWR) is most commonly detected by physical examination and diagnosed by a tissue biopsy for confirmation and for hormone receptor and HER2-neu analysis. A staging workup is necessary to plan the appropriate therapy and is primarily performed by PET-CT. In the absence of distant metastases, CWR should be considered for surgical local excision if the lesion is not fixed to the underlying intercostal bony structures or sternum and if the recurrent lesions are not multiple and diffuse on the chest wall or associated with diffuse skin thickening and erythema requiring neoadjuvant chemotherapy or hormonal therapy. In a patient with an ER/PR-positive HER2-neu (-) local recurrence without distant metastases, adjuvant hormonal therapy followed by surgery for local excision should be primarily considered. Adjuvant radiotherapy is indicated in patients without prior postmastectomy radiation therapy. CWR in patients with autologous reconstruction should be locally excised without reconstruction or prosthesis removal. Therefore, no standard treatment for patients with CWR is available. Reirradiation for bulky disease may be considered in patients in whom surgery and chemotherapy are not considered. Hyperthermia or photodynamic treatment may also provide alternative therapeutic options for the management of these patients. A tissue biopsy for diagnosis and hormone receptor and HER2-neu evaluation should be established along with a full metastatic workup. If no distant metastases are noted and the regional recurrence is operable, surgical excision should be considered as the first-line treatment. In hormone receptor (HR)-positive patients, endocrine therapy should be changed or started followed by surgery, whereas chemotherapy should be administered in triple-negative patients followed by surgery. Similarly, anti-HER2-neu therapy with or without chemotherapy and/ or endocrine therapy should be considered (e.g., trastuzumab, pertuzumab, lapatinib, TDM-1) in patients with HER2-neu positivity. Therefore, systemic therapies should be personalized to each individual patient. © Springer International Publishing Switzerland 2016.

WOS: 000382992100003, PubMed ID: 28331745, Objective: Breast cancer is the most common malignancy among Turkish women and the rate of early stage disease is increasing. The Oncotype DX 21-gene assay is predictive of distant recurrence in ER-positive, HER2-negative early breast cancer. We aimed to evaluate the correlations between Recurrence Score (RS) and routine risk factors. Materials and Methods: Ten academic centers across Turkey participated in this prospective trial. Consecutive patients with breast cancer who had pT1-3, pN0-N1mic, ER-positive, and HER2-negative tumors were identified at tumor conferences. Both pre- and post-RS treatment decisions and physician perceptions were recorded on questionnaire forms. Correlations between RS and classic risk factors were evaluated using univariate and multivariate analyses. Results: Ten centers enrolled a total of 165 patients. The median tumor size was 2 cm. Of the 165 patients, 57% had low RS, 35% had intermediate RS, and 8% had high RS, respectively. Multivariate analysis indicated that progesterone receptor (PR) and Ki67 scores were significantly related to RS. Conclusion: Oncotype DX Recurrence Score does not seem to have a significant correlation with the majority of classic risk factors, but it may have a correlation with PR score and Ki67 score., Genomic Health (Inc.; California, USA), Genomic Health (Inc.; California, USA) has provided an educational grant for the genomic testing in this trial.

The TNM staging system for breast cancer as described by the American Joint Committee on Cancer (AJCC) was introduced to act as a standard tool to assess the prognosis of patients with newly diagnosed breast cancer. In 2009, the 7th revised edition of the TNM system was published to reflect updates in technology and clinical evidence. In the new staging system, the presence of isolated tumor cells or micrometastases in the axillary lymph nodes was found to have little impact on survival. Furthermore, breast cancer therapy has evolved with the increasing application of neoadjuvant therapy, and therefore, additional pretreatment and posttreatment staging were incorporated into the new staging system to determine chemotherapy response and treatment efficacy. Rapid advances in both clinical and laboratory sciences along with translational research have raised questions about the feasibility of ongoing TNM staging to determine whether to apply systemic therapy based on anatomic prognosis. Although multigene expression assays, such as the 70-gene prognostic signature or Oncotype DX tests, may provide additional prognostic and predictive information beyond anatomic TNM staging and ER/PR and HER2 status, there might be difficulties in incorporating these biomarkers into the TNM system. With advances in personalized medicine, more molecular gene assays and new prognostic and predictive markers such as tumor-infiltrating lymphocytes might be incorporated into future staging systems.

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).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) (p0.001), 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.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.

In a significant proportion of patients, the sentinel lymph node (SLN) is the only involved axillary node. The goal of the present study was to identify predictive factors associated with a positive SLN and with a positive non-SLN in patients in whom axillary lymph node dissection (ALND) was performed.Data was reviewed for patients with T1-2 invasive breast cancer who underwent SLN biopsy with or without axillary dissection in a single institution between July 2000 and May 2010. The SLNs were examined by serial sectioning and HE staining, and by cytokeratin immunostaining in suspicious cases.Of 332 patients with SLNB, 134 had SLN positivity, and 116 of them further underwent completion axillary dissection. Patients with T2 tumors (OR=3.2; 95% CI, 1.74-5.58), or tumors with lymphovascular invasion (OR=8.0; 95% CI, 4.44-14.27), or invasive ductal cancer (OR=2.92; 95% CI, 1.1-8.0) were more likely to have a positive SLN. In patients with ALND, the non-SLN involvement rates were 10%, 11.5% and 50% in patients with isolated tumor cells (ITC), micrometastasis and macrometastasis, respectively. Finding of ITC or micrometastasis in SLNs (OR=0.28; 95% CI, 0.08-0.99) or presence of extracapsular invasion (ECI) in SLN (OR=0.24; 95% CI, 0.09-0.67) were the predictive factors of not having a non-SLN metastasis in logistic regression analysis.These findings suggest further axillary surgery can be best omitted in patients with micrometastasis while validation of nomograms including factors such as ECI are still needed to be studied in patients with macrometastasis.

Background More than half of re-excision specimens after breast conserving surgery (BCS) are found to be free of residual tumor at definitive histology. The aim of this study was to identify clinicopathological factors along with intrinsic subtypes of the tumor (luminal A, luminal B, HER2-overexpressing, triple-negative) associated with residual tumor in re-excision or mastectomy specimen. Methods Two hundred forty-eight patients with initial BCS, who underwent one or more re-excisions or mastectomy because of close or positive margins were reviewed. Results Residual cancer was found in 50% of re-excision(s) or mastectomy specimens. Patients with multifocality (vs unifocality; OR = 5.2; 95% CI, 2.6–10.4) or positive nodes (vs negative nodes; OR = 2.5; 95% CI, 1.4–4.4), or positive margins (vs close margins; OR = 1.7; 95% CI = 1.0–2.9) were more likely to have residual tumor in re-excision or mastectomy specimen compared to others. Conclusion Our results suggest that further surgery is often indicated in patients with node positive or multifocal cancers or positive margins after BCS since residual disease cannot be ruled out. Re-excision or mastectomy could be omitted in patients with close margins with favorable factors such unifocal tumor or node negative disease.

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.

Aim: Lymphedema is a serious complication associated with axillary surgery and/or radiotherapy in patients with breast cancer. The aim of this randomized study was to assess the efficacy of two different treatment modalities of lymphedema by comparing the manual lymphatic drainage and compression bandage with intermittent pneumatic compression and self-lymphatic drainage. Material and Methods: Thirty patients diagnosed with lymphedema after treatment for breast cancer were randomized to either manual lymphatic drainage (MLD)by physicotherapists with compression bandage-group (n=15) or to the intermittent pneumatic compression (IPC)-group with self-lymphatic drainage massage (n=15). In both groups, treatment program was performed three days a week, every other day for 6 weeks. To determine the efficacy of the treatment modalities, arm circumferences were measured from wrist to shoulder girdle with 10 cm distance before and after treatment for lymphedema at the 1st, 3rd, and 6th weeks of the therapies. Tests evaluating the quality of life including EORTC-QLQ and ASES-test were also performed before and after treatment at 6th week. Results: The median age of patients was 54.5 years (31-74) and lymphedema occured after a median time of 18 months following surgery (range, 6-72 months). Patients in both groups had similar demographic and clinical characteristics. At the 6th week, even though both treatment modalities resulted in significant decreases (p< 0.001) in the total arm volume (12.2% decrease in IPC-group versus 14.9% decrease in MLD-group), no significant difference could be found in the therapeutic efficacy between the IPC-and MLD-groups. Furthermore, significant improvements of ASES scores were detected after both IPC-and MLD-therapies (p=0.001), but there was no statistically significance between two groups. In the EORTC-QLQ-C30 quality of life test, however, global health status, functional and cognitive functioning scores appeared to be improved only after MLD-therapy, whereas emotional functioning scores, fatique and pain scores significantly improved after MLD-or IPC-therapy. Conclusion: Both treatment modalities by MLD and IPC appear to be effective in the treatment of lymphedema with similar therapeutic efficacy in patients with breast cancer. MLD-therapy seems to be superior to IPC-therapy since there is a trend of an improvement in the quality of life in patients treated with MLD. However, IPC might still be the preferred treatment for some patients who work at the day time since it could be performed easily at home by themselves without a need for a physicotherapist at the hospital. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-15-04.

Objective: This study aims to determine the feasibility of a population-based organized mammography screening in a developing country (Bahcesehir, Istanbul, Turkey) and to find out the starting age for screening. Material and methods: Women aged 40–69 were invited for screening at 2-year intervals starting in January 2009. Digital 2-view mammograms were obtained, and mammograms were double read by two independent radiologists who were experienced in breast imaging. The women were recalled in consensus for additional work-up including spot compression/magnification mammograms or breast ultrasound. Outcomes were measured from final assessment or histopathologic confirmation. The participation rate for second round, recall rate, number of biopsies, the women diagnosed with cancer and patient and tumor characteristics were evaluated. Results: Between January 2009 and January 2013, 5938 (89.4%) of 6640 women aged between 40-69 years old accepted mammographic invitation. Most of them (58%) were at 40-49 age group, and the average 2-year attendance for second rounds were 82.6% and 81.2%, respectively. Spot recall rates were 16.8% and 25.6% for the first and second rounds, respectively. Core biopsy was required in 108 patients (1.8%), whereas BC was diagnosed in 50 patients (0.84%). Twenty-four patients (48%) detected with BC were at 40-49 age group. There were 39 patients (78%) with invasive BC and 11 patients (22%) with ductal carcinoma in situ (DCIS). Stages of 39 patients with invasive BC were Stage I (n = 26; 52%), II (n = 10; 20%) and III (n = 3; 6%), respectively. The majority of patients (88%) had breast conserving surgery, and sentinel lymph node biopsy only (72%) as axillary procedure. Of invasive cancers, 92% were found to be hormone receptor positive, and 59% had low Ki67 levels (≤15). However, HER2-neu positivity (8%) along with triple negative cancers (3%) were less frequently detected. Conclusion: These findings suggest the prevailing view that mammographic screening increases early breast cancer detection rate which has a less aggressive biology. Screening mammography program can be successfully implemented in a developing country, Turkey effectively. However, more experienced dedicated breast cancer screening team and continuous increasing efforts are required to decrease our relatively high recall rates. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-04-06.

Background: We investigated the expression of CXCR4, CCR7, estrogen receptor (ER), progesterone receptor (PR) and HER2-neu in human metastatic breast cancers to determine whether these biological biomarkers were preferentially expressed in any organ-specific metastases. Materials and methods: CXCR4, CCR7, ER, PR and HER2-neu expression levels were evaluated by immunohistochemical staining using paraffin-embedded tissue sections of metastatic breast cancers (n = 41) obtained by either diagnostic biopsy or surgical resection. Results: The metastatic sites included the following: bone (n = 15), brain (n = 14), lung (n = 6), liver (n = 2), and omental metastases (n = 2). CXCR4 was expressed in 41% of cases, CCR7 expression was demonstrated in 10%, and HER2-neu overexpression was present in 27%. CXCR4 was more likely to be expressed in bone metastases than visceral metastases (67% versus 26%, P = 0.020). Visceral sites demonstrated a lower rate of CXCR4 positivity (33% and 23%, respectively, for lung and brain metastases). Similarly, CCR7 was more likely to be found in bone metastases than visceral sites (27% versus 0%, P = 0.037). Conclusions: These results indicate that CXCR4 can contribute to the homing of breast cancer cells to the bone. This finding might have important clinical implications since patients with metastatic bone disease may achieve the highest benefit from a CXCR4-targeted therapy.

Chemokines are chemoattractant cytokines that regulate the trafficking and activation of leukocytes and other cell types under a variety of inflammatory and noninflammatory conditions. Over the past few years, studies have increasingly shown that chemokines play an important role in several aspects of tumor progression. Tumor cells express functional chemokine receptors, which can sustain proliferation, angiogenesis, and survival and promote organ-specific localization of distant metastases. Chemokine expression in human malignancies is associated with a leukocyte infiltration favoring the establishment of immune escape mechanisms. A literature review of relevant publications on preclinical testing of cancer therapies based on interference with the cancer chemokine network was performed. The feasibility, potential advantages, and limitations of the clinical translation of the results of such studies in treatment of different tumor types and settings are discussed. The chemokine network is a key player in the establishment of metastases. In the preclinical setting, blocking agents and antibodies directed against CXCR4 prevent metastasis of different cancers. In mouse models, overexpression of selected chemokines causes tumor infiltration by distinct leukocyte subsets, resulting in tumor regression and tumor-specific immunity generation. Researchers have also successfully used chemokines as carriers and/or adjuvants for cancer vaccines. The cancer chemokine network is a multifaceted therapeutic target.

Purpose: Recent studies have indicated that expression of chemokine receptors CXCR4 and CCR7 could be an indicator of the metastatic potential of breast cancer. Expression of CXCR4 and CCR7 along with the biomarkers HER2-neu and epidermal growth factor receptor (EGFR) was investigated in inflammatory breast cancer (IBC) to evaluate their prognostic implications. Experimental design: CXCR4, CCR7, and EGFR were evaluated by immunohistochemical staining (IHC) of paraffin-embedded tissue sections. HER2-neu amplification was assessed by FISH and/or IHC. All patients received chemotherapy, surgery, and radiation. Results: Forty-four cases diagnosed with IBC from 1994 to 2002 were included in the study. In all, 18 (40.9%) patients had positive CXCR4, 10 (22.7%) had positive CCR7, 21 (47.7%) had positive HER2-neu, and EGFR was positive in 12 of 40 patients (30%). The 5-year overall survival (OS) was 24.8% for CXCR4-positive disease versus 42.3% for CXCR4-negative patients (P = 0.53) and 20.0% for CCR7-positive disease versus 41.9% for CCR7-negative patients (P = 0.24). EGFR-positive disease had significantly worse OS compared with EGFR-negative disease (P = 0.01). Conclusions: These data demonstrate the expression of growth factor and chemokine receptors in IBC. The expression of these receptors is associated with increased risk of recurrence and death, and thus, they may represent potential therapeutic targets in IBC.

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.

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.

Background Recent studies have suggested that chemokine receptors are involved in development of organ-specific pattern of metastases. In the present study, we evaluated the association between the chemokine receptors expressed in primary tumor cells and the site of metastatic relapse in patients with breast cancer. Methods Primary tumors were obtained from 142 patients with axillary node–positive breast cancer and stained for CX3CR1, CXCR4, CCR6, and CCR7 expression. All statistical analyses were adjusted for systemic post-operative treatment. Results After a median follow-up of 13 years, none of the chemokine receptors was associated with overall survival or disease free survival. However, expression of chemokine receptors was found to be associated with increased risk of relapse in certain organs. By estimating the Mantel-Haenszel odds ratios (OR), CXCR4 was associated with increased risk of metastasis to the liver (OR = 3.71, P = 0.005), CX3CR1 was associated with metastasis to the brain (OR = 13.18, P = 0.01). Patients with CCR6 positivity were more likely to develop a first metastasis in the pleura (OR = 2.82, P = 0.06). In addition, CCR7 expression was associated with the occurrence of skin metastases (11% versus 0%, P = 0.017). Interpretation Expression of chemokine receptors in the primary tumor predicts the site of metastatic relapse in patients with axillary node positive breast cancer. This study, in concordance with the data obtained in animal models, suggests that the chemokine receptors family could be the biological support of the ‘seed and soil’ theory.

Experimental evidence suggests that CXCR4, a Gi protein–coupled receptor for the ligand CXCL12/stromal cell–derived factor-1α (SDF-1α), 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-1α 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-1α–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-1α–stimulated cell migration. We report a novel mechanism of HER2-neu transactivation through SDF-1α stimulation of CXCR4 that involves Src kinase activation.

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.

Granulomatous mastitis (GM) is a rare inflammatory breast disease of unknown etiology. Although it usually presents with sinus formation and abscesses, it may mimic the clinical characteristics of breast cancer. The aim of this study was to identify the clinical, radiologic, and pathologic characteristics of patients with GM and to show the results of surgical treatment in these patients. A chart review was performed for patients that were treated with a diagnosis of GM at the Breast Unit, Department of Surgery, Istanbul Medical Faculty, University of Istanbul, between September 1998 and January 2003. Eighteen patients were eligible for this study. The median age was 41.5 years (range 16–80 years). Seventeen patients were evaluated by both ultrasonography and mammography; whereas one young patient only had ultrasonography. Three patients were further examined with color Doppler ultrasonography and magnetic resonance imaging (MRI). Fourteen patients (78%) presented with a mass as the chief symptom, with a median size of 3.9 cm (range 1–8 cm), whereas four patients presented with fistula in their breasts. None of the radiologic techniques distinguished benign disease from cancer in any of the 14 patients that presented with a mass except one patient with normal mammography findings. Ultrasonography was only helpful to localize the abscess associated with a fistula tract in one patient. Therefore fine-needle aspiration biopsy (FNAB) was performed in six patients, followed by surgical excisional biopsy. The remaining eight patients with a clinical suspicion of malignancy underwent wide surgical excision with frozen section analysis under general anesthesia. All of the FNAB and frozen section evaluations revealed benign findings. All of the 18 patients underwent a wide excisional biopsy and had a definitive histopathologic diagnosis of GM. The median follow-up was 36 months (range 6–60 months). Only one patient had a recurrent disease, which was diagnosed at 12 months. GM is a rare breast disease that mimics cancer in terms of clinical findings. Preoperative radiologic diagnosis might be difficult. Complete surgical excision is the treatment of choice.

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.

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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 2004. © 2004 American Cancer Society.

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.

Twenty-three patients with inflammatory breast cancer treated with a combined modality approach including anthracycline-based induction chemotherapy-surgery-chemotherapy-radiotherapy were reviewed. Twelve patients (52.2%) received FAC (5-fluorouracil, adriamycin, cyclophosphamide) and 11 patients (47.8%) were treated with FEC (5-fluorouracil, epirubicin, cyclophosphamide) induction chemotherapy for three cycles every 3 weeks. Surgery was followed by the initial chemotherapy or second-line chemotherapy for an additional six cycles to complete nine cycles and radiotherapy, respectively. The median overall survival (OS) time was 27 months and the median disease-free survival (DFS) was 13 months. Furthermore, patients treated with FAC induction chemotherapy have been found to have longer median OS and DFS periods compared to patients with FEC induction chemotherapy in both univariate and multivariate analysis. In conclusion, the superiority of doxorubicin-containing chemotherapy over epirubicin-containing chemotherapy should be established in larger randomized studies and more effective chemotherapeutic agents such as taxans are required for better survival rates in inflammatory breast cancer patients.

Background 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. Study design 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. Results 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). Conclusions 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.

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 multi-focal 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.

Intrabiliary rupture is the most common complication of hepatic hydatid disease (HHD), and persistent biliary leakage is the most frequent complication after surgery for HHD. In this study, we evaluated the outcome of endoscopic sphincterotomy (ES) performed in the management of postoperative biliary fistula in 33 patients with HHD and investigated the effects of the daily output of the fistula and the timing of the ES on the duration of the fistula.Between January 1994 and April 2000, 33 patients (20 female, 13 male; median age, 44 years; range, 17-72) underwent ES at our clinics. The daily output of the biliary fistula ranged from 100 ml to 1000 ml (mean, 430 ml; in 18 patientsor = 400 ml; in 15 patients,400 ml). The interval between the occurrence of the fistula and the performance of the ES ranged from 7 days to 5 months (median, 20 days; in 12 patients,or = 2 weeks; in 21 patients2 weeks).In patients with fistula output 400 ml (n = 18) and400 ml (n = 15), the average closure times for the fistula after ES were 10.7 +/- 4.5 and 10.4 +/- 4.9 days, respectively (t-test: p = 0.847, t = 0.195). In patients (n = 2) with a short interval between the occurrence of the fistula and ES (2 weeks), the average closure time for the fistula was 11.6 +/- 5.6 days, whereas for the patients (n = 15) with longer intervals (2 weeks) it was 9.4 +/- 3.9 days (t = test: p = 0.254, t = 1.180). The drainage from the fistula stopped after an average of 9.88 +/- 4.83 days in all patients who underwent ES, and there were no any complications. Pearson's correlation test (PC) showed no significant relationship between the time for the complete closure time of the fistula after ES and the fistula output (PC=-0.253, p=0.155) or for the duration of the fistula before endoscopic retrograde cholangio pancreatography (ERCP) (PC = -0.333, p = 0.058).Endoscopic sphincterotomy is safe and effective and should be considered the minimally invasive procedure of choice for the management of postoperative biliary fistula due to HHD because it obviates the need for reoperation. If the sphincterotomy is successful, neither the daily output not the duration of the fistula has any influence on the time required for complete closure of the fistula.

Background Whether sentinel lymph node biopsy (SLNB) should be performed in patients with pure ductal carcinoma in situ (DCIS) of the breast has been a question of debate over the last decade. The aim of this study was to identify factors associated with microinvasive disease and determine the criteria for performing SLNB in patients with DCIS. Materials and methods 125 patients with DCIS who underwent surgery between January 2000 and December 2008 were reviewed to identify factors associated with DCIS and DCIS with microinvasion (DCISM). Results 88 patients (70.4%) had pure DCIS and 37 (29.6%) had DCISM. Among 33 DCIS patients who underwent SLNB, one patient (3.3%) was found to have isolated tumor cells in her biopsy, whereas 1 of 14 (37.8%) patients with DCISM had micrometastasis (7.1%). Similarly, of 16 patients (18.2%) with pure DCIS and axillary lymph node dissection (ALND) without SLNB, none had lymph node metastasis. Furthermore, of 20 patients with DCISM and ALND, only one (5%) had metastasis. In multivariate analysis, the presence of comedo necrosis [relative risk (RR)=4.1, 95% confidence interval (CI)=1.6-10.6, P=0.004], and hormone receptor (ER or PR) negativity (RR=4.0, 95%CI=1.5-11, P=0.007), were found to be significantly associated with microinvasion. Conclusions Our findings suggest patients presenting with a preoperative diagnosis of DCIS associated with comedo necrosis or hormone receptor negativity are more likely to have a microinvasive component in definitive pathology following surgery, and should be considered for SLNB procedure along with patients who will undergo mastectomy due to DCIS.

To date, BRCA1 and BRCA2 mutations in breast and/or ovarian patients have not been characterized in the Turkish population. We investigated the presence of BRCA mutations in 53 individuals with a personal and family history of breast and/or ovarian cancer, and 52 individuals with a personal history of breast cancer diagnosed below age 50 without additional family history. We have identified 11 mutations (nine BRCA1 and two BRCA2) using combined techniques involving protein truncation test, direct sequencing and heteroduplex analysis. We found eight out of 53 patients (15.1%) with a family history to carry BRCA gene mutations (seven BRCA1 and one BRCA2). Of these, four were found in 43 families presenting only breast cancer histories, and four were found in families presenting ovarian cancer with or without breast cancer. We also demonstrated two BRCA1 and one BRCA2 mutations in three out of 52 (5.8%) early-onset breast cancer cases without additional family history. Three of nine BRCA1 and both BRCA2 mutations detected in this study were not reported previously. These mutations may be specific to the Turkish population. The BRCA1 5382insC mutation, specific to Ashkenazi and Russian populations, was found twice in our study group, representing a possible founder mutation in the Turkish population. © 2000 Cancer Research Campaign

1005Background: The MF07-01 trial is a multicenter phase III randomized trial of treatment naive stage IV BC patients comparing loco-regional surgery (LRS) followed by appropriate systemic therapy (ST) vs ST alone. Aims: To compare 3-year survival and loco-regional progression (LRP). Methods: At initial diagnosis patients were randomized 1:1 to LRS group or ST group. After consideration of retrospective studies, we hypothesized at 36 months a survival difference between the two groups to be 18%. Assuming a 10% drop out rate and with a one sided log-rank test with a 95% CI and a 90% power 271 patients needed to be randomized. Results: 274 patients were accrued; 138 in the LRS group and 136 in the ST group. The groups were comparable regarding age, BMI, HER2 neu, tumor type and size, histologic grade, and bone and visceral metastasis (all p > 0.05). There were 76 (55%) deaths in the LRS group and 101 (74%) in the ST group during the median 40 (20-51) months follow-up. At 36 months the survival rate was simi...

Introduction. Sentinel lymph node biopsy (SLNB) in patients with pure ductal carcinoma in situ (DCIS) has been a matter of debate due to very low rate of axillary metastases. We therefore aimed to identify factors in a single institutional series to select patients who may benefit from SLNB. Material and Methods. Patients, diagnosed with pure DCIS () between July 2000 and March 2011, were reviewed. All the sentinel lymph nodes were examined by serial sectioning (50 μm) of the entire lymph node and H&E staining, and by cytokeratin immunostaining in suspicious cases. Results. Median age was 51 (range, 30–79). Of 63 patients, 40 cases (63.5%) with pure DCIS underwent SLN, and 2 of them had a positive SLN (5%). In both 2 cases with SLN metastases, only one sentinel lymph node was involved with tumor cells. Patients who underwent SLNB were more likely to have a tumor size >30 mm or DCIS with intermediate and high nuclear grade or a mastectomy in univariate and multivariate analyses. Conclusion. In our series, we found a slightly higher rate of SLNB positivity in patients with pure DCIS than the large series reported elsewhere. This may either be due to the meticulous examination of SLNs by serial sectioning technique or due to our patient selection criteria or both.

Rapidly growing mycobacteria are pathogens responsible for cutaneous or subcutaneous infections especially occurring after injection, trauma or surgery. We describe a patient with Mycobacterium abscessus mastitis that presented as a mass lesion and haemorrhagical discharge. It was initially diagnosed and treated as fibrocystic disease and non-specific abscess. Full recovery was obtained with combination therapy of clarithromycin, linezolid and amikacin without surgical debridement followed by several abscess aspirations. Atypical mycobacteria should be considered in diagnosis of chronic breast lesions in endemic areas. This is the first reported case of mastitis due to M. abscessus in Turkey.

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.