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Simple Summary Most breast cancers are small and can be treated using breast-conserving surgery. Since these tumors are non-palpable, they require a localization step that helps the surgeon to decide which tissue needs to be removed. The oldest localization technique is a guidewire placed into the tumor before surgery, usually using ultrasound or mammography. Afterwards, the surgeon removes the tissue around the wire tip. However, this technique has several disadvantages: It can cause the patient discomfort, requires a radiologist or another professional specialized in breast diagnostics to perform the procedure shortly before surgery, and 15-20% of patients need a second surgery to completely remove the tumor. Therefore, new techniques have been developed but most of them have not yet been examined in large, prospective, multicenter studies. In this review, we discuss all available techniques and present the MELODY study that will investigate their safety, with a focus on patient, surgeon, and radiologist preference. Background: Surgical excision of a non-palpable breast lesion requires a localization step. Among available techniques, wire-guided localization (WGL) is most commonly used. Other techniques (radioactive, magnetic, radar or radiofrequency-based, and intraoperative ultrasound) have been developed in the last two decades with the aim of improving outcomes and logistics. Methods: We performed a systematic review on localization techniques for non-palpable breast cancer. Results: For most techniques, oncological outcomes such as lesion identification and clear margin rate seem either comparable with or better than for WGL, but evidence is limited to small cohort studies for some of the devices. Intraoperative ultrasound is associated with significantly higher negative margin rates in meta-analyses of randomized clinical trials (RCTs). Radioactive techniques were studied in several RCTs and are non-inferior to WGL. Smaller studies show higher patient preference towards wire-free localization, but little is known about surgeons\" and radiologists\" attitudes towards these techniques. Conclusions: Large studies with an additional focus on patient, surgeon, and radiologist preference are necessary. This review aims to present the rationale for the MELODY (NCT05559411) study and to enable standardization of outcome measures for future studies.

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 pa-tients 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 dif-ference 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 pa-thology, as long as axillary radiotherapy is provided. (c) 2021 Published by Elsevier Ltd., Istanbul Breast Society, This project has been supported by the Istanbul Breast Society.

Background: Expression of immune checkpoint receptors (ICR) on tumor infiltrating lymphocytes (TILSs) is associated with better response to immunotherapies via immune checkpoint inhibitors. Therefore, we investigated various ICR expressions on TILs in patients with locally advanced triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC). Methods: Expressions of ICRs were examined immunohistochemically by staining surgical specimen (n=61) using specific monoclonal antibodies for PDL-1, PD-1, TIM-3, LAG-3, CTLA-4. Positivity was defined staining >1% on TILs. Results: Median age was 49 (24-76) years. The majority patients were clinically T3-4 (n=31, 50.8%), and clinically N1-3 (n=58, 95.1%) before NAC. Of those, 82% were found to have CTLA-4 positivity, whereas TILs associated positivites for PD1, PDL-1, LAG3 and TIM-3 were 62.3%, 50.9%, 26.2%, 68.9%. High expression of CTLA-4 was found to be associated with a better chemotherapy response (OR=7.94, 95%CI: 0.9-70.12, p=0.06), whereas TIM-3 positivity was contrarly associated with a worse chemotherapy response (OR=0.253, 95%CI: 0.066-0.974, p=0.047) as measured by MDACC Residual Cancer Burden Index. At a 47-month follow-up, patients with ypN0 disease (DFS; HR=0.31, 95% CI: 0.12-0.83, p=0.02 and DSS; HR=0.21, 95% CI:0.07-0.62, p=0.005) and CTLA-4 high expression on TILs (DFS; HR=0.38, 95% CI=0.17-0.85, p=0.019 and DSS; HR=0.34, 95% CI:0.15-0.78, p=0.01) were found to have improved survival. Conclusions: These findings demonstrate that CTLA-4, PD-1, PDL-1 and TIM-3 were highly expressed in TNBC after NAC. Our results more favor an immuncheckpoint inhibitor therapy via CTLA-4 alone or in combination with other immune check point inhibitors against PDL-1 and/or TIM-3 in addition to NAC in advanced TNBC. Citation Format: Neslihan Cabioglu, Semen Onder, Gizem Oner, Hüseyin Karatay, Mustafa Tukenmez, Mahmut Muslumanoglu, Abdullah Igci, Yesim Eralp, Adnan Aydiner, Pinar Saip, Ekrem Yavuz, Vahit Ozmen. Tim3 expression on tumor infiltrating lymphocytes is associated with poor response to neoadjuvan chemotherapy in patients with locally advanced triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-32.

BACKGROUND: Omitting axillary lymph node dissection (ALND) following sentinel lymph node biopsy (SLNB) in patients with locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NAC) is still controversial. In this study, we evaluated factors affecting local recurrence and outcome in patients with LABC, who underwent SLNB alone after NAC. METHODS: Between 2004 to 2018, 320 patients with clinically node-positive LABC who received NAC and underwent SLNB alone after negative axillary staging were analyzed. All patients had breast and/or regional nodal irradiation. RESULTS: Median age was 46 (23-70). Of those, 228 patients had ypN0 disease (71.25%), whereas 92 patients had ypN(+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastasis (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 37 months (24-172), one patient (0.3%) with macrometastatic SLN having extracapsular extension was found to have locoregional recurrence at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were found as 87% and 95%, respectively. Patients with cT3&4 (HR=2.22, 95% CI; 1.07-4.62), non-luminal molecular pathology (HR=2.71, 95% CI, 1.23-5.97), and non-pCR in the breast (HR=2.21, 95% CI, 0.94-5.17) were found to have an increased HR compared to others in 5-year DFS. However, no significant differences could be found between patients ypN0, ypN-ITC&micrometastasis and ypN-macrometastasis regarding 5-year DFS and DSS rates. CONCLUSIONS: ALND could be safely avoided in selected patients with LABC who underwent SLNB after NAC having cT1-2, luminal pathology, breast and/or nodal pCR or low volume nodal disease, as long as axillary radiotherapy is provided. Citation Format: Neslihan Cabioglu, Hasan Karanlık, Mahmut Muslumanoglu, Guldeniz Karadeniz Çakmak, Didem Can Trablus, Mustafa Tukenmez, Yeliz E. Ersoy, Cihan Uras, Baha Zengel, Selman Emiroğlu, Ayfer Kamalı Polat, Levent Yeniay, Enver Ozkurt, Halil Kara, Kamuran Ibis, Adnan Aydiner, Vahit Ozmen, Abdullah Igci. Sentinel lymph node biopsy alone in locally advanced breast cancer after neoadjuvant chemotherapy: Turkish multicentric neosenti-turk MF-18-02-study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-26.

Immune checkpoint receptors (ICRs) were recently found to modulate the anti-tumoral immune response. This study aimed to determine the clinical and pathological associations of ICRs expression on tumor-infiltrating lymphocytes (TILs) in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (NAC). Expressions of ICRs including PD-1, LAG-3, TIM-3, TIGIT, and CTLA-4 on CD8+ T lymphocytes and Natural Killer (NK) cells on TILs were analyzed by flow cytometry. Patients < 50 years were more likely to express CTLA-4 on CD8+ T lymphocytes compared to those ≥ 50 years (p = 0.004). In addition, patients with ypT3-4 tumors were more likely to have increased LAG-3 expression on CD16-CD56bright NK cells (p = 0.042) and PD-1 (p = 0.014) and CTLA-4 (p = 0.018) expressions on CD8+ T cells in regard to those with ypT1-T2, respectively. Contrarily, PD-1 expression on CD16-CD56bright NK cells was found to be decreased in patients with ypN+ compared to those with ypN- (p = 0.022). Furthermore, patients with HER2+ tumors were more likely to have increased TIM-3 expression on CD8+ T cells (p = 0.043), whereas patients with a better response to NAC were more likely to express TIGIT on CD8+ T (p = 0.014) and CD16- CD56bright NK cells (p = 0.003), respectively. The new generation ICRs, TIM-3, LAG-3, and TIGIT are highly expressed in LABC following NAC in patients with poor prognostic factors. Therefore, new evolving therapies using inhibitory mAbs directed to TIM-3, LAG-3, and TIGIT could be also be considered in locally advanced breast cancers expressing these ICRs.

Background and Objectives: Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer treated up-front with systemic treatment. Both breast-conserving surgery and sentinel lymph node biopsy (SLNB) are controversial issues in the management of IBC. In this study, we aimed to assess the feasibility of SLNB in pathologically proven node-positive IBC patients. Methods: All patients with a histopathological diagnosis of IBC and biopsy-proven metastatic axillary lymph nodes underwent systemic treatment. Patients with a complete clinical response in the axilla who underwent SLNB followed by standard axillary dissection were analyzed. Results: The study consisted of 25 female patients. The identification rate (IR) and the false negativity rate (FNR) were 17/25 and 2/10, respectively. Overall, 9/25 and 7/25 of patients had a complete pathological response (pCR) in the breast and axilla after systemic treatment, respectively. Although the pCR in the axilla was 2/4 in nonluminal HER2-positive patients, the highest IR 4/4 and the lowest FNR 0/2 were determined in these patients. In triple-negative patients, however, the IR was 2/4 and the FNR was found to be 0/2. Conclusions: SLNB may be considered in selected axilla-downstaged IBC patients including patients with a pCR with HER2-positive and triple-negative tumors. Axillary dissection may be, therefore, omitted in those with negative SLNs.

Background: Metaplastic breast carcinoma (MBC) is a rare type of breast cancer that accounts for 0.2–1% of all breast cancers. To date, there are only few institutional studies comparing survival rates between different subtypes. In this retrospective cohort study, we aim to evaluate factors effecting survival rates of different subtypes of MBC. Methods: This retrospective cohort study observed 118 nonmetastatic MBC patient records extracted from 15,244 breast cancer cases between December 2000 and December 2020. In order to analyze factors effecting survival rates of mesenchymal subtype of MBC, all cases are classified as mesenchymal (n = 45) and other (n = 48). Twenty-five cases could not be sub-classified due to the missing data. Univariate and multivariate logistic regression analyses were performed to define factors associated with survival rates. Results: Of the 15,244 cases, 118 (0.8%) were nonmetastatic MBC. 105 were triple negative and 12 were nonluminal HER2. There was no significant difference between mesenchymal and other subgroups for age, median tumor size, AJCC staging, and type of surgery. Of the five local recurrences with known subgroup, four of them had mesenchymal subtype. It is demonstrated that mesenchymal subtype was significantly associated with worse 5-year disease-free survival and disease-specific survival (HR: 2.35 [1.01–5.48], p = 0.049, and HR: 3.16 [1.06–9.47], p = 0.040 with 95% CI, respectively). Conclusion: This study is one of the few studies presenting the survival outcomes of subtypes of MBCs. Nonetheless, it is the only study demonstrating that mesenchymal subtype had worse survival outcomes. Further studies are needed to determine the outcome of different subtypes of MBCs.

OBJECTIVE: We aimed to compare visual and quantitative measurements of breast density and to reveal the density profile with compression characteristics. MATERIALS AND METHODS: Screening mammograms of 1399 women between May 2014 and May 2015 were evaluated by using Volpara 4(th) and 5(th) version. First 379 mammograms were assessed according to ACR BI-RADS 4(th) edition and compared to Volpara. We categorized the breast density in two subgroups as dens or non-dens. Two radiologists reviewed the images in consensus. Agreement level between visual and volumetric methods and volumetric methods between themselves assessed using weighted kappa statistics. Volpara data such as fibroglandular volume (FGV), breast volume (BV), compression thickness (CT), compression force (CF), compression pressure (CP) were also analyzed with relation to the age. RESULTS: 1399 mammograms were distributed as follows: 12.7% VDG1, 39.3% VDG2, 34.1% VDG3, 13.9% VDG4 according to the 4th edition of Volpara; 1.2% VDG1, 46% VDG2, 36.8% VDG3, 15.9% VDG4 according to the 5(th) edition of Volpara. The difference between two editions was 4.7% increase in dense category. 379 mammograms, according to ACR BI-RADS 4(th) edition, were distributed as follows: 25.9% category A, 50.9% category B, 19.8% category C, 3.4% category D. The strength of agreement between the Volpara 4(th) and 5(th) editions was found substantial (k=0.726). The agreements between visual assessment and both Volpara editions were poor (k=−0.413, k=-0.399 respectively). There was a 142% increase in dense group with the VDG 4(th) edition and 162% with the VDG 5(th) edition when compared to visual assessment. Compression force decreased while compression pressure increased with increasing Volpara Density Grade (VDG) (p for trend

Objective: Primary neuroendocrine carcinoma of the breast (NECB) is a rare distinct type of breast carcinoma. There is limited data about the optimal management, treatment, and prognosis. Therefore, we analyzed the clinicopathological features, management and the clinical outcome of this rare breast carcinoma. Material and Methods: Patients diagnosed as NECB between July 2008 and January 2018 were included in the study. Medical records were retrospectively reviewed. Results: A total of 4,896 breast cancer patients were reviewed and 18 NECB (0.4% of all cases) were extracted. The median age was 61.5 (30-82). Thirteen cases (72.2%) underwent breast conserving surgery. Eight patients had axillary lymph dissection. All of the cases were pathological T1 and T2. Only one patient was pathological stage 3. Median tumor size was 20.5mm (10- 45). Only two cases presented with small cell subtype, the rest were well-differentiated. Hormone receptor was positive and HER2/neu was negative for all cases. Of the 15 patients with known Ki-67, three had high expressions (≥20%). No local or distant disease recurrences and death related with NECB were detected at a median follow-up period of 101 months (33-148). Conclusion: NECB is more likely to be hormone receptor positive and HER2/neu negative as luminal A or B subtype. An excellent clinical outcome is remarkable despite a substantial number of patients with axillary lymph node positivity specifically for well-differentiated subtype. Less invasive treatment options should be kept in mind., Amaç: Nöroendokrin meme karsinomu (NMK) nadir görülen ve özellikli bir meme tümörüdür. Bu alt tipin tedavisi ve prognozu ile ilgili bilgiler sınırlıdır. Çalışmamızda, bu nadir görülen tümörün klinikopatolojik özelliklerini, tedavisini ve klinik sonuçlarını inceledik. Gereç ve Yöntemler: Temmuz 2008 ve Ocak 2018 tarihleri arasında NMK tanısı alan hastaların verileri retrospektif olarak incelendi. Bulgular: Toplam kayıtlı 4896 meme kanseri hastasının 18’i NMK idi (toplam vakaların %0,4’ü). Ortanca yaş 61,5 (30-82) olarak bulundu. On üç hastaya (%72,2) meme koruyucu cerrahi uygulandı. Sekiz hastaya ise aksiller lenf nodu diseksiyonu yapıldı. Sadece bir hasta patolojik evre 3 iken tüm hastalar patolojik olarak T1 ve T2 idi. Ortanca tümör boyutu 20,5 mm (10-45) olarak bulundu. Sadece iki hasta küçük hücreli alt tipi iken 16 hasta iyi-diferansiye alt tipindeydi. Tüm hastalar hormon reseptör pozitif ve HER2/ neu negatifti. Ki-67 değeri bilinen 15 hastadan 3 tanesinde yüksek Ki-67 değeri (>%20) mevcuttu. Ortanca 101 (33-148) aylık takip süresinde lokal-bölgesel veya uzak rekürrens görülmedi. On sekiz hastada hastalığa bağlı ölüm görülmedi. Sonuç: NMK genellikle hormon reseptör pozitif ve HER2/neu negatif olacak şekilde luminal A veya B olarak tespit edilmektedir. Aksilla pozitif hastalar olsa da özellikle iyi-diferansiye alt grupta sağ kalımlar çok iyidir. Bu hastalarda daha az girişimsel tedavi seçenekleri göz önünde bulundurulmalıdır.

The assessment of immune infiltrate in invasive breast carcinomas (IBCs), most commonly referred to as tumor infiltrating lymphocytes (TILs), is gaining importance in the current quest for optimal biomarker selection and prediction of prognosis. In this study, the impact of intensity of TILs and expressions of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death-1 (PD-1), and lymphocyte activation gene 3 (LAG-3) in a group of breast carcinomas with regards to the prognosis and conventional pathologic parameters was scrutinized. For this purpose, 238 patients with IBCs containing different proportions of TILs were included in the study. IBCs with higher proportion of TILs were usually grade III carcinomas and correlated with poor prognostic features like receptor negativity, nonluminal intrinsic subtype (P

Objective Hamartomas are rare, slowly-growing breast tumours. Clinical, radiological and histopathological examination together increase the diagnostic accuracy. To evaluate the clinicopathologic features of hamartomas and outline our clinical approach to hamartomas in our 20-year experience at our Breast Clinic. Materials and methods Between 1995 and 2015, 24 cases were retrospectively analyzed with a diagnosis of breast hamartoma at our Breast Clinic followed by excisional biopsy. Data was obtained on patient demographics, clinical examination, radiological findings and histopathological subtypes. Results Of 1338 benign breast tumours excised from January 1995 to January 2015, 24 (1.8%) were identified as breast hamartoma. Median age of patients was 42 (range, 13-70), whereas the median tumour size was 5 cm (1-10 cm). On preoperative imaging, hamartoma was most commonly misdiagnosed as fibroadenoma. Pathological examination of the 24 biopsy specimens revealed 3 cases with pseudoangiomatous stromal hyperplasia, and another hamartoma associated with a radial scar within the centre of the lesion. Of those, one patient was diagnosed with malignant phylloides tumour in the same breast. At a median follow-up 58.4 months, none of the patients recurred or developed malignancy. Conclusion Hamartomas can often be missed by clinicians, due to its benign nature which is poorly understood. Despite their slow growth, hamartomas can reach large sizes and can cause breast asymmetry. Although it is rare, hamartoma can be seen along with malignancy, as it is formed from similar components of breast tissue. Therefore, careful diagnosis and appropriate management including surgery are required.

Background Studies on PD-L1 expression in breast cancer have gained importance in recent years, especially in triple-negative breast cancer (TNBC). Our aim was to analyze the differential expression of PD-L1 to explore its correlation with response to neoadjuvant chemotherapy (NACT) and patient survival. Methods PD-L1 expression was evaluated immunohistochemically (Ventana SP263 clone kit) by staining tumor specimen. PD-L1 positivity was defined as membranous staining > 1%, > 5%, > 10%, and > 20% on either tumor cell (TC) and /or immune cell (IC). Results Fifty patients with locally advanced TNBC, who had a partial response to NACT, were included in the study. PD-L1 staining was observed in TCs in 25 patients (50%) and in ICs in 23 patients (46%) when PD-L1 > 1% was considered positive. Patients with PD-L1 positivity on ICs were more likely to respond to chemotherapy as measured by “MD Anderson Cancer Center Residual Cancer Burden Index” (14/22, 63.6% vs. 10/27, 37%, p = 0.064). The 5-year disease-free survival (DFS) and disease-specific survival (DSS) rates were 46.3% and 51.4%, respectively. A high (> 20%) tumoral PD-L1 positivity was associated with a better DFS and DSS. Conclusions Studies in the literature mostly focused on PD-L1 expression in inflammatory cells. However, our results suggest that patients with a high PD-L1 expression on TCs were more likely to have a better outcome. Since patients with residual tumor burden who express PD-L1 on TILs were more likely to respond to NACT, an immune checkpoint inhibitor therapy in addition to NACT would be an important option for TNBC with locally advanced disease.

Background The aim of this randomized clinical trial was to evaluate the overall survival (OS) data of patients diagnosed with de novo stage IV breast cancer (BC) who received locoregional treatment (LRT) over a 10-year follow-up. Study Design The MF07-01 is a 1:1 multicenter, randomized clinical trial comparing the LRT with systemic therapy (ST), where ST was given to all patients either immediately after randomization or after surgical resection of the intact primary tumor. Results A total of 278 patients were randomized and 265 patients were in the final analysis. At 10-year follow-up, survivals were 19% (95% CI 13%–28%) and 5% (95% CI 2%–12%) in the LRT group and ST group, respectively. Median survival was 46 months for the LRT group and 35 months for the ST group, and hazard of death was 29% lower in the LRT group compared with the ST group (hazard ratio [HR] 0.71; 95% CI 0.59–0.86; p = 0.0003). Conclusions Patients with a diagnosis of de novo stage IV BC who underwent LRT followed by ST had a 14% higher chance of OS by the end of the 10-year follow-up compared with the patients who received only ST. The longer study follow-up revealed that LRT should be presented to patients when discussing treatment options.

Background The expression of immune checkpoint receptors (ICRs) on tumor-infiltrating lymphocytes (TILs) is associated with better response to immunotherapies via immune checkpoint inhibitors. Therefore, we investigated various ICR expressions on TILs in patients with locally advanced triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC). Methods Expressions of ICRs were examined immunohistochemically in surgical specimens (n = 61) using monoclonal antibodies for PDL-1, PD-1, TIM-3, LAG-3, and CTLA-4. Positivity was defined as staining > 1% on TILs. Results The median age was 49 (24–76) years. The majority of patients were clinically T3–4 (n = 31, 50.8%) and clinically N1–3 (n = 58, 95.1%) before NAC. Of those, 82% were found to have CTLA-4 positivity, whereas PD1, PDL-1, LAG3, and TIM-3 expressions on TILs were 62.3, 50.9, 26.2, and 68.9%. A high expression of CTLA-4 was found to be associated with a better chemotherapy response (OR = 7.94, 95% CI: 0.9–70.12, p = 0.06), whereas TIM-3 positivity was contrarily associated with a worse chemotherapy response (OR = 0.253, 95% CI: 0.066–0.974, p = 0.047) as measured by the MDACC Residual Cancer Burden Index. At a 47-month follow-up, ypN0 (DFS; HR = 0.31, 95% CI: 0.12–0.83, p = 0.02 and DSS; HR = 0.21, 95% CI: 0.07–0.62, p = 0.005) and CTLA-4 high expression on TILs (DFS; HR = 0.38, 95% CI: 0.17–0.85, p = 0.019 and DSS; HR = 0.34, 95% CI: 0.15–0.78, p = 0.01) were found to be associated with improved survival. Conclusions These findings demonstrate that CTLA-4, PD-1, PDL-1, and TIM-3 were highly expressed in TNBC. Based on these high expression patterns, further studies directed towards combined therapies are warranted in advanced TNBC in future.

Highlights • Weight and the BMI are inadequate proxies for adiposity that do not distinguish between muscle and adipose tissue or different specific deposits of adipose tissue (visceral and subcutaneous), which have different physiological effects. • Patients with the same BMI are likely to have different anatomical distribution of adipose and muscle tissue. • To our knowledge, only few studies have investigated the association between fat and muscle tissue distribution of the body, and response to neoadjuvant chemotherapy., Purpose To compare the adipose and muscle tissue areas in patients who responded differently to neoadjuvant chemotherapy. Methods One hundred and eighty six patients diagnosed with breast cancer who underwent neoadjuvant chemotherapy between January 2015- October 2019 and were operated after the treatment were retrospectively included in the study. Pathological results were divided into five groups using the Miller-Payne grading systems. Grade 1 indicating no significant reduction in malignant cells; Grade 2: a minor loss of malignant cells (≤ 30 %); Grade 3: reduction in malignant cells between 30 % and 90 %; Grade 4: disappearance of malignant cells >90 %; Grade 5: no malignant cells identifiable. Pre-treatment PET CT scans were evaluated, and calculation of body composition parameters were performed on a single axial section passing through the L3 vertebrae. Spearman’s correlation test was used to analyze the correlation between SAT, VAT, MT parameters and pathological responses. Results There was no strong correlation between the 5 groups separated according to neoadjuvant chemotherapy treatment response and tissue distributions. However, that there was a very low correlation found between superficial adipose tissue and pathological response (r=, 156). Conclusion In conclusion, our results have provided a very low correlation between SAT and more than 30 % response. More research is required to evaluate the role of the body fat and muscle parameters in response to neoadjuvant chemotherapy in larger patient populations.

PURPOSE The Turkish Bahceehir Breast Cancer Screening Project was a 10-year, organized, population-based screening program carried out in Bahceehir county, Istanbul. Our aim was to examine the biologic features and outcome of screen-detected and interval breast cancers during the 10-year study period. METHODS Between 2009 and 2019, 2-view mammograms were obtained at 2-year intervals for women aged 40 to 69 years. Clinicopathological characteristics including ER, PR, HER2-neu, and Ki-67 status were analyzed for those diagnosed with breast cancer. RESULTS In 8,758 screened women, 131 breast cancers (1.5%) were detected. The majority of patients (82.3%) had prognostic stage 0-I disease. Contrarily, patients with interval cancers (n = 15; 11.4%) were more likely to have a worse prognostic stage (II-IV disease; odds ratio [OR], 3.59, 95% CI, 0.9 to 14.5) and high Ki-67 scores (OR, 3.14; 95% CI, 0.9 to 11.2). Interval cancers detected within 1 year were more likely to have a luminal B (57.1% v 31.9%) and triple-negative (14.3% v 1%) subtype and less likely to have a luminal A subtype (28.6% v 61.5%; P = .04). Patients with interval cancers had a poor outcome in 10-year disease-specific (DSS) and disease-free survival (DFS) compared with those with screen-detected cancers (DSS: 68.2% v 98.1%, P = .002; DFS: 78.6% v 96.5%, P = .011). CONCLUSION Our findings suggest the majority of screen-detected breast cancers exhibited a luminal A subtype profile with an excellent prognosis. However, interval cancers were more likely to have aggressive subtypes such as luminal B subtype or triple-negative cancers associated with a poor prognosis requiring other preventive strategies. (c) 2020 by American Society of Clinical Oncology RocheRoche Holding; Basaksehir (Basaksehir county in Istanbul) Municipality Supported by a grant from Roche (V.O.) and Basaksehir (Bahcesehir is a region in the Basaksehir county in Istanbul) Municipality.

Identification and resection of a clipped node was shown to decrease the false-negative rate (FNR) of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) for patients presenting with initially node-positive breast cancer. Between March 2014 and March 2016, a prospective trial analyzed 98 patients with axilla-positive locally advanced breast cancer (T1-4, N1-3) to assess the feasibility and efficacy of placing clips into most suspicious biopsy-proven node. The study considered blue, radioisotope active, and suspiciously palpable nodes as sentinel lymph nodes (SLNs). The SLN identification rate was 87.8%. The median age of the patients with an SLNB (n = 86) was 44 years (range 28–66 years). Of these patients, 77 (88.4%) had cT1-3 disease, and 10 (11.6%) had cT4 disease. The majority of the patients (n = 66, 76.7%) had cN1, whereas 21 patients (23.3%) had cN2 and cN3. A combined method was used for 37 patients (43%), whereas blue dye alone was used for the remaining patients (57%). The clipped node was the SLN in 70 patients (81.4%). For the patients with cN1 before NAC, the FNR was found to be 4.2% (1/24) when the clipped node was identified as an SLN. However, the FNR was estimated to be as high as 16.7% (1/6) for the patients with cN1 before NAC when the clipped node was found to be a non-SLN. The study results also suggest that axillary dissection could be omitted for patients presenting initially with N1 disease and with a negative clipped node as the SLN after NAC due to the low FNR.

Background: Novel systemic therapies are under investigation for patients with triple negative breast cancer who are resistant to neoadjuvant chemotherapy or having a partial response to neoadjuvant chemotherapy. Immune check point inhibition or blocking other immunologic markers such as chemokine receptors might be alternative pathways for these chemotherapy-resistant patients. Therefore, we investigated various immune check point receptor expressions along with different chemokine receptors. Method: Expressions of immunological markers were examined immunohistochemically by staining archival tissue of mastectomy specimen (n=56) using specific monoclonal antibodies for PDL-1 (Ventana SP263 clone kit), CXCR4, CXCR5, CCR5, CCR7, CD73, and CD155. PDL-1 positivity was defined as membranous staining >1% in either tumor and /or stromal lymphocytes, whereas positivity of chemokine receptors and CD155 and CD73 were considered as cytoplasmic staining >50% and >5%, and >1%, respectively. Results: Median age was 47 (24-76) years. Of those, 31 were clinically T3-4 (55%), whereas almost all of them were N1-3 (96.4%) before neoadjuvant chemotherapy. All patients received anthracyclines&paclitaxel containing regimens, whereas 3 patients received additional carboplatin before definitive surgery. Of those, 30 patients (58%) were detected to be positive for PDL1 in tumor site and intratumoral lmyphocytes, whereas CXCR5 (41.1%, 23/56) , CCR5 (48.2%, 27/56), CCR7 (41.1%, 23/56), CD155 (30/56, 58%) and CD73 (44.6%, 25/56) were found to be highly expressed in tumors. However, 12.5% of patients have shown high expression of CXCR4. Patients with CXCR5, CCR5, CCR7, CD73, CD155 positivity were more likely found to give a worse chemotherapy response as measured by “Residual Cancer Burden Index”. Table 1.Associations between MD Anderson Residual Cancer Burden Index and Immunological Biomarker ExpressionsTumor characteristicsClass IClass 2&3P-valueCXCR4-negative8.3%91.7%0.999CXCR4-positive0%100% CXCR5-negative12.5%87.5%0.131CXCR5-positive0%100% CCR5-negative14.3%85.7%0.111CCR5-positive0%100% CCR7-negative12.5%87.5%0.131CCR7-positive0%100% CD73-negative13.3%86.70.117CD73-positive0%100% CD155-negative16%84%0.037CD155-positive0%100% PDL1-negative4.895.20.999PDL1-positive3.396.7% Median follow-up time was 36 months (7-177). Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were found to be decreased in patients with CXCR4 (DFS: negative, 55% vs positive, 23%; p= 0.079 and DSS: negative, 52% vs positive, 23%; p=0.034) and CCR5 positivity(DFS: negative, 63.5% vs positive, 26%; p= 0.037 and DSS: negative, 61% vs positive, 25%; p=0.047), while no significant difference could be found in DFS and DSS rates in regards to PDL1, CXCR5, CCR7, CD73 and CD155 positivity. Conclusion: These results demonstrate that PDL-1, CD73, CD155 and chemokine receptors are highly expressed in patients with partial response to neoadjuvant chemotherapy. Furthermore, expressions of CXCR4 and CCR5 were found to be associated with poor prognosis in this cohort with triple negative breast cancer resistant to chemotherapy that would justify an addititional chemokine receptor inhibitor therapy. Citation Format: Cabioglu N, Onder S, Oner G, Karatay H, Tukenmez M, Muslumanoglu M, Igci A, Dinççag A, Aydiner A, Saip P, Ozmen V, Yavuz E. High expressions of CXCR4 and CCR5 are associated with poor prognosis in triple negative breast cancer resistant to neoadjuvan chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-26.

e12597 Background: In this study, we aimed to assess the outcomes, and predictors of recurrence in patients with early-stage node-negative breast cancer. Methods: We evaluated data of the patients who were treated between 1988 and 2018 years retrospectively. Demographical, clinical, pathological, and treatment features of the patients were recorded. SPSS 25 version was used for statistical analysis. We used Kaplan-Meier and Cox regression analysis to assess survival analysis. Also, we performed logistic regression and ROC analysis for recurrence predictors. Results: In total, 347 patients were included in the study.The median age was 50 (range, 18-81) at diagnosis. The percent of the patients who had stage 1 and 2 were 86.6% and 13.4%, respectively. The most common histopathological type was invasive ductal carcinoma (71.6%). Estrogen receptor and progesterone receptor positivity were 80.3% and 62.1%, respectively. Her2 receptor positivity was 15.9%. The number of patients who had undergone lumpectomy and mastectomy was 85.5% and 14.5%, respectively. Sentinel lymph node biopsy was performed on 78.7% of the patients, and axillary lymph node dissection 21.3%. Also, the patients received adjuvant radiotherapy (88.7%), adjuvant chemotherapy (48.5%), and adjuvant hormonotherapy (82.1%). Tumor recurrence was occurred in 31 (8.7%) patients (local recurrence-45.2% and metastasis-54.8%). Five-, ten- and twenty-years recurrence ratios were 4.3%, 8%, and 23%. Also, contralateral breast cancer has occurred in 19 (5.3%) patients. During the study period, 30 (8.4%) patients died. Ten-years and twenty-years survival ratios were 91.6% and 76.6%, respectively. In univariate analysis, aged over 65 years (p = 0.004), nuclear pleomorphism (p = 0.049), mitosis (p = 0.003), and necrosis (p = 0.002) were statistically significant for recurrence. In ROC analysis, the tumor's longest size was not statistically significant for recurrence (for over 1.45 cm, p = 0.07). Conclusions: In this study, we determined thirty-years outcomes in patients with early-stage node-negative breast cancer. In the follow-up, we detected the recurrences ratios, between ten and twenty years, were more common than the first ten-years. Despite a small number of patients who had a recurrence, we showed that being age over 65 years and pathological features (nuclear pleomorphism, mitosis, and necrosis) were statistically significant for disease recurrence in univariate analysis.

Background: The MF07-01 trial is a multicenter phase III randomized controlled trial of treatment naive stage IV BC patients comparing loco-regional surgery (LRS) followed by appropriate systemic therapy (ST) versus ST alone. Aims: To evaluate the importance of loco-regional tumor burden and surgery on overall survival rate in patients with de novo stage IV breast cancer. Methods: At initial diagnosis patients were randomized 1:1 to LRS group or ST group. The surgery was a lumpectomy (L) or mastectomy (M) and sentinel lymph node biopsy (SLNB) ± axillary lymph node dissection (ALND). After surgery all patients received systemic treatment + endocrine treatment (ET) and Trastuzumab based on pathology results. The demographic, pathologic, and clinical characteristics of the patients were recorded. 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). In the LRS group 36 patients (26%) had L+ALND, 92 patients (67%) had M+ALND and 10 patients (7%) had M+SLNB, respectively. The patients and tumor characteristicsPatients and Tumors Characteristics and Surgical TreatmentSurgerySystemic TherapyP ValueAge (mean /year±SD)51.8 ±12.651.5±13.6NSMedian follow-up (25%,75%)41.0 (24,54)37 (18,49) Tumor Size (%) T18.7 (12) NST252.2 (72) NST321.7 (30) NST417.4 (24) NSHistologic Grade (%) I4.4 (6)9.6 (10)NSII39.9 (55)31.7 (33)NSIII55.8 (77)58.9 (61)NS Surgical Treatment Lumpectomy+ ALND26 (36)--M + SLNB7 (10)--M + ALND67 (92)---SLNB17 (23)--ALND92.8 (128)--pN+89.1 (123)--30-day mortality1.4 (2)1.5 (2)0.98SLNB-Sentinel Lymph Node Biopsy; ALND-Axillary Lymph Node Dissection; M-Mastectomy The axillary positivity rate was 89.1%. There were 76 (55%) deaths in the LRS group and 101 (74%) in the ST group during the median 40 (20-51) month follow-up. Overall survival (OS) was 34% higher in the LRS group compared to the ST group (HR: 0.66, 95%CI 0.49-0.88: p = 0.005). Overall survival rate was higher in LN (+) (p=0.01), tumor size Conclusion: In this subgroup analysis, we observed that patients with high grade tumor, without skin or chest wall involvement and positive axilla who underwent surgery for primary breast tumor and axilla had better overall survival than ST in de novo stage IV breast. These results can be considered in clinical research design for stratification. Citation Format: Ozmen V, Ozbas S, Karanlik H, Muslumanoglu M, Igci A, Canturk Z, Utkan NZ, Ozaslan C, Evrensel T, Uras C, Aksaz E, Soyder A, Ugurlu UM, Col C, Cabioglu N, Bozkurt B, Sezgin E, Dagoglu T, Uzunkoy A, Dulger M, Koksal N, Cengiz O, Gulluoglu B, Unal B, Atalay C, Yildirim E, Erdem E, Salimoglu S, Sezer A, Koyuncu A, Gurleyik G, Alagol H, Ulufi N, Berberoglu U, Soran A. The importance of loco-regional tumor burden and surgery on survival in patients with de novo stage IV breast cancer; post-hoc analyses of protocol MF07-01 [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-16-01.

Recent randomized trials have shown that completion axillary lymph node dissection (ALND) is not required in all patients with a positive sentinel lymph node (SLN) who will receive radiation therapy. Although routine intraoperative pathologic assessment (IPA) becomes unnecessary and less indicated by breast surgeons in the United States and some European countries, it is still widely used all around the world. In this prospective study, the feasibility of intraoperative nodal palpation (INP) as opposed to IPA of the SLN has been analyzed. Between March 2014 and June 2015, 305 patients with clinical T1-2/N0 breast cancer from two different breast clinics (cohort A; [n = 225] and cohort B; [n = 80]) who underwent any breast surgery with sentinel lymph node biopsy (SLNB) were included in this study. Surgeons evaluated the SLNs by manual palpation before sending for IPA, and findings compared with the final pathology. The positive predictive values (PPV) of INP and IPA were 81.8% and 97.9%, respectively, whereas the negative predictive values (NPV) of INP and IPA were 83% and 92.4%. The accuracies of INP and IPA were 82.6% and 94.1%, respectively. If patients with SLNB including micrometastasis were also considered in the final pathologic assessment (FPA) (-) group that would not require a further axillary dissection, the revised NPV of INP and FPA were found to be 92.6% and 98.1%, respectively. The revised accuracy of INP also found to be increase to 86.9%. Our study, which is the only prospective one about palpation of dissected SLNs in the literature, suggests that INP can help to identify patients who do not need ALND, which encourages omitting IPA in cT1-2 N0 breast cancer.

Background: Recent advances in tumor biology and immune system have identified check points modulating the anti-tumoral immune response. This study aimed to determine immune check point expressions patients with locally advanced breast cancer to explore any associations between clinical and prognostic factors to show effectiveness of targeted therapies for these molecules. Materials and Methods: This prospective study was carried out between September 2018 and November 2019 in the Department of General Surgery of Istanbul University Istanbul Faculty of Medicine Breast Unit. Twenty-four patients with LABC with a partial response to neoadjuvant chemotherapy (NAC) were included in the study. Tumor infiltrating lymphocytes (TILs) were isolated from the residual tumor burden separated from the surgical material with cell dissociation kit by using MACS tumor separation device. Expressions of immune checkpoints receptors including PD-1, LAG-3, TIM-3, TIGIT and CTLA-4 on CD8 T lymphocytes and Natural Killer (NK) cell subsets obtained from TIL were analyzed by using flow cytometry. Results: TILs of patients Conclusion: Our results suggest that patients with a younger age and advanced tumor burden are more likely to benefit from immunotherapeutical approaches using immune check point inhibitors. Furthermore, combination of systemic chemotherapy with immunotherapy may increase the pathologic response rate in breast cancer patients. Citation Format: Ayxan Abbasov, Esin Çetin, Neslihan Cabioglu, Baran Mollavelioglu, Semen Onder, Selman Emiroglu, Mustafa Tukenmez, Mahmut Muslumanoglu, Abdullah Igci, Gunnur Deniz, Vahit Ozmen. Differential expressions of immune check point receptors on tumor infiltrating lymphocytes after neo-adjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 947.

Introduction: High expression of immune checkpoint receptors in tumor microenvironment reduces antitumor immunity and cause immune evasion of tumor cells. In recent years, immunotherapy trials using PD-1 or PDL-1 inhibitors in advanced triple negative (TN) breast cancer evolved very rapidly. The differential expression of novel immune checkpoint receptors such as TIM-3, LAG-3 and TIGIT in addition to PD-1, and CTLA-4 on tumor infiltrating lymphocytes (TIL) in patients with early breast cancer was investigated. Material and methods: TIL were isolated by using a Tumor Dissociation Kit from fresh tumoral tissue. Flow-cytometric analyses were performed by using CD8, CD16, CD56, PD-1, CTLA-4, TIM-3, LAG-3 and TIGIT specific monoclonal antibodies on isolated TIL. Correlations were estimated between biological and clinical characteristics of tumors and demographic features of patients and flow cytometric findings. Results: Median age was 47 (range 28-68). There were 7 patients (35%) with HER2+ or triple negative tumors, whereas 13 patients (65%) had HER2 (-) luminal cancers. Our findings showed that patients younger than 45 years were more likely to express high levels of CTLA-4 (p=0.013) and TIGIT (p=0.007) on CD56+ natural killer (NK) cells and TIM-3 (p=0.043) on CD16+ lymphocytes (Table 1), whereas the other high expressions including LAG-3 (p=0,08) and TIM-3 (p=0.06) on CD56+ NK cells did not reach the statistical significance. Furthermore, patients with high Ki-67 proliferation index >35% were found to express higher CTLA-4 (p=0.011) on CD16+ lymphocytes. Patients with Stage II disease expressed higher levels of PD-1 (p=0.018) and LAG-3 (p=0.04) on CD8+ cytotoxic T lymphocytes than patients with Stage I disease. Similarly, patients with lymph node metastasis had higher TIGIT (p=0.04) and PD-1 (p=0.05) levels on CD16+ and CD56+ lymphocytes, respectively. No other significant associations could be found between immune check receptors and other parameters. Conclusion: Our results suggest TIL in patients with more advanced stages and younger than 45 years old are more likely to express higher levels of immune checkpoint receptors such as LAG-3, TIM-3, CTLA-4, TIGIT and PD-1. Interestingly, no difference could be found in immune checkpoint receptor expressions in TIL between patients with luminal and TN or HER2+, that would justify immunotherapeutical approaches in selected luminal breast cancers in future trials. Table 1. Significant correlations between immune check point receptor expression and demographic and tumor features CD8PD1CD8LAG3CD16CTLA4CD16TIGITCD16TIM3CD56CTLA4CD56TIGITCD56PD1meanpmeanpmeanpmeanpmeanpmeanpmeanpmeanpAge45 (n:13)9.739.699.049.548.548.087.8810.62Ki-67 (cut off %35) All statistical analyses were evaluated using the Mann Whitney U test. Citation Format: Baran Mollavelioglu, Esin Aktas Cetin, Neslihan Cabioglu, Aykhan Abbasov, Semen Onder, Selman Emiroglu, Mustafa Tukenmez, Mahmut Muslumanoglu, Abdullah Igci, Gunnur Deniz, Vahit Ozmen. Differential expression of novel immune checkpoint receptors expressed on tumor-infiltrating lymphocytes (TIL) in patients with early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-24.

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.