Favorable outcome with sentinel lymph node biopsy alone after neoadjuvant chemotherapy in clinically node positive breast cancer at diagnosis: Turkish Multicentric NEOSENTI-TURK MF-18-02-study.

PURPOSE: Factors affecting local outcome were evaluated in patients with clinically node-positive (cN+) breast cancer at diagnosis, who underwent sentinel lymph node biopsy (SLNB) alone after neoadjuvant chemotherapy (NAC). METHODS: Between 2004 and 2018, 303 cytopathology-proven cN (+) patients in a multicentric registry, who received NAC and underwent SLNB alone were analysed. All patients had regional nodal irradiation. RESULTS: Median age was 46 (23-70). Of those, 211 patients had ypN0 disease (69.6%), whereas 92 patients had ypN (+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastases (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 36 months (24-172), one patient (0.3%) with macrometastatic SLN was found to have locoregional recurrence as chest wall and supraclavicular LN metastases at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were 87% and 95%, respectively. Patients with cT3/4 (HR = 2.41, 95% CI; 1.14-5.07), non-luminal molecular pathology (HR = 2.60, 95% CI, 1.16-5.82), and non-pCR in the breast (HR = 2.11, 95% CI, 0.89-5.01) were found to have an increased HR compared to others in 5-year DFS. However, no difference could be found between ypN0 and ypN ITC and micrometastasis (HR = 1.23, 95% CI, 0.44-3.47), whereas there was a slight increase in HR of patients with ypN macrometastasis versus ypN0 (HR = 1.91, 95% CI, 0.63-5.79). CONCLUSION: ALND could be avoided in meticulously selected cN (+) patients who underwent SLNB after NAC having breast and/or nodal pCR, cT1-2, or low volume residual nodal disease with luminal pathology, as long as axillary radiotherapy is provided.

Preoperative chemotherapy for T2 breast cancer is associated with improved surgical outcome.

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.

The use of Ligasure vessel sealing system in axillary dissection; effect on seroma formation.

BACKGROUND: Seroma formation is the most frequent postoperative complication after axillary dissection for breast surgery with an incidence of 10 - 50 %. This prospective clinical randomized study was carried out to evaluate the Ligasure vessel sealing system and its effect on seromaformation and other complications for axillary dissection. METHODS: Between January 2006 and November 2007, the patients with histopathological diagnosis of breast cancer were analysed prospectively. The patients with positive sentinel lymph node biopsy or clinical axillary involvement were included in the study, and the patients who underwent neoadjuvant therapy or using anticoagulants have been excluded from the study. Patients were divided into two study groups.Axillary dissection was performed in the first group by LigaSure and in the second group by linking and electrocautery. RESULTS: There were a total of thirty three patients with a mean age of 51.4 +- 13.7. In group one, mean age of patients was 54.1 +- 13.2 and 48.68 +- 14.1 in group two. There was no significant statistical difference between the groups regarding age, body mass index, excised tissue weight,tumour size and number of excised lymph nodes. The use of Ligasure reduced drainage amount and duration of drain till removal, but increased operative time. CONCLUSION: There were no significant differences between study groups regarding the complications. LigaSure electrothermal bipolar vessel sealing system can be safely used in axillary dissection as an alternative to traditional methods.

Sentinel Lymph Node Biopsy in Pure DCIS: Is It Necessary?

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 (n = 63) 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.

Factors predicting the non-sentinel lymph node involvement in breast cancer patients with sentinel lymph node metastases.

OBJECTIVE: 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. METHODS: 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 H&E staining, and by cytokeratin immunostaining in suspicious cases. RESULTS: 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. CONCLUSIONS: 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.

Positive or close margins in breast conserving surgery: is re-excision always necessary?

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.

Successfully treated Mycobacterium abscessus mastitis: a rare cause of breast masses.

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.

Chemokine receptors in advanced breast cancer: differential expression in metastatic disease sites with diagnostic and therapeutic implications.

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.

Primary ovarian cancer presenting with axillary lymph node metastases: a report of two cases.

BACKGROUND: Axillary lymph node metastasis of primary ovarian cancer is rare. CASE I: A 74-year-old woman presented with a 2 x 2 cm hard, mobile mass in the right axilla. She had a history of stage IIIA epithelial ovarian cancer which was diagnosed and treated four years previously. A right lateral wall involvement of the rectum was detected in abdominal tomography. A right axillary lymph node dissection and low anterior resection of the rectum were performed. Histopathologic examination showed ovarian epithelial serous papillary adenocarcinoma metastases to axillary lymph node and the rectum. CASE 2: A 38-year-old woman presented with a 3 x 2 cm hard, mobile mass in the right axilla. She was treated surgically and by systemic chemotherapy with a diagnosis of stage IIIA epithelial ovarian cancer two years previously. A trucut biopsy was taken from the enlarged axillary lymph node, and histopathological examination revealed metastases of primary ovarian cancer. Complete axillary lymph node dissection was performed and metastases of ovarian papillary adenocarcinoma were found in 11 of the 30 lymph nodes. CONCLUSION: Supradiaphragmatic lymph node involvement of primary ovarian cancer is very rare. We report here two cases presenting with axillary metastases of ovarian cancer.

Expression of growth factor and chemokine receptors: new insights in the biology of inflammatory breast cancer.

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.

Sentinel lymph node biopsy for breast cancer: current controversies.

Sentinel lymph node biopsy (SLNB) has replaced the routine level I and II axillary lymph node dissection (ALND) for women with clinically node-negative T1 and T2 breast cancer. Studies have shown that SLNB is highly predictive of axillary nodal status with a false-negative of rate less than 10%. Our purpose was to address some of the ongoing controversies about this procedure, including technical issues, use of preoperative lymphoscintigraphy, internal mammary lymph node biopsy, criteria for patient selection (in intraductal carcinoma?), its staging accuracy, and the clinical approach when a SLNB was found to be negative or positive on pathologic examination. After the revision of the American Joint Committee on Cancer (AJCC) staging system for breast cancer in 2002, the evaluation of internal mammary lymph nodes and determination of micrometastases by hematoxylin-eosin or by immunohistochemistry have become increasingly important in staging of patients. Recent guideline recommendations developed by the American Society of Clinical Oncology (ASCO) Expert Panel in 2005 are also discussed. Long-term follow-up results of ongoing studies will provide more accurate assessment of the prognostic significance of SLNB and its value in the prevention of breast cancer-related morbidity in axillary staging compared to ALND.

Expression of chemokine receptors predicts the site of metastatic relapse in patients with axillary node positive primary breast cancer.

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.

Factors predicting the sentinel and non-sentinel lymph node metastases in breast cancer.

The sentinel lymph node (SLN) is the only focus of axillary metastasis in a significant proportion of patients. In this single institutional study, clinicopathologic characteristics were investigated to determine the factors predicting the status of a SLN biopsy and the metastatic involvement of non-SLNs. Data were retrospectively reveiwed for 400 consecutive patients with clinical T1/T2 N0 breast cancer who underwent a SLN biopsy including axillary and/or internal mammary lymph nodes. The SLNs were evaluated by using the new AJCC staging criteria following multiple sectioning and immunohistochemical (IHC) analyses of nodes. The SLN contained metastases in 148 patients (38.5%) including 18 patients (12.2%) with micrometastases (0.2 cm). Five patients had isolated tumor cells detected by IHC (

Endoscopic sphincterotomy in the management of postoperative biliary fistula A complication of hepatic hydatid disease.

BACKGROUND: 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. METHODS: 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 patients < or = 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 patients >2 weeks). RESULTS: In patients with fistula output 400 ml (n = 18) and >400 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). CONCLUSIONS: 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.

Endoscopic ligation for patients with active bleeding Mallory-Weiss tears.

BACKGROUND: Only a few patients with active nonesophageal variceal upper gastrointestinal bleeding have been treated with endoscopic ligation. To further address this issue, four patients with active bleeding Mallory-Weiss tears who underwent endoscopic band ligation are presented. PATIENTS AND METHODS: Endoscopic ligation was performed in four patients with a median age of 52 years (range, 40-93 years) after a diagnosis of active bleeding Mallory-Weiss tears (MWTs). A 45-year-old man with massive persistent upper gastrointestinal bleeding as a cause of a MWT underwent therapeutical endoscopic band ligation after an unsuccessful endoscopic injection trial. On the contrary, injection therapy should have been performed on a 93-year-old woman with multiple myeloma because of an actively bleeding MWT caused by the fibrotic tissue after an unsuccessful endoscopic ligation trial, although her other actively bleeding MWT lesion had been ligated successfully. RESULTS: After endoscopic ligation, all patients achieved complete hemostasis, and rebleeding did not occur. They were discharged without complications after a control endoscopy. CONCLUSIONS: Endoscopic ligation can be performed easily and without any complications such as perforation or delayed hemorrhage in patients with actively bleeding nonfibrotic MWTs.

Biological considerations in locally advanced breast cancer treated with anthracycline-based neoadjuvant chemotherapy: thymidine labelling index is an independent indicator of clinical outcome.

The present retrospective study aims to determine the clinical value of thymidine labelling index (TLI) together with other established clinical and biological factors in 116 locally advanced breast cancer (LABC) patients treated with anthracycline-based neoadjuvant chemotherapy, surgery, adjuvant chemotherapy and radiotherapy. TLI was determined in 71 LABC patients with a median of 2.62% (0-23.64%) and a mean of 4.71% +/- 5.54. As a result of neoadjuvant chemotherapy, 85 patients (73%) responded to chemotherapy (CT), whereas 31 patients were unresponsive (27%). No relationship has been found between the pretreatment biological variables including TLI, estrogen receptor (ER), progesteron receptor (PgR) status and clinical parameters such as the chemotherapy response rates and axillary lymph node involvement following chemotherapy. Median follow-up was 35 months (18-97 months) and the 3-year overall survival (OS) and disease free survival (DFS) rates were 71.6% and 52.2%, respectively. In univariate analysis, patients with inflammatory breast cancer, high TLI-index (> or = 2.62%), lymph node (LN) positivity or > 3 positive lymph nodes following neoadjuvant chemotherapy and without any response to neoadjuvant chemotherapy were found to have worse DFS and OS-rates and high local and systemic recurrence rates. In multivariate analysis, TLI was estimated as the most powerful independent factor affecting the OS in LABC patients among the other established clinical and biological parameters (p = 0.02). These results suggest that TLI is an important independent indicator of clinical outcome in patients with LABC and these patients with high TLI levels require more effective treatment modalities.

BRCA1 and BRCA2 mutations in Turkish breast/ovarian families and young breast cancer patients.

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.