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Immunological dysfunction has been suggested to play a major role in the pathogenesis of idiopathic granulomatous mastitis (IGM). We recently showed that ozone therapy was effective in patients with steroid-resistant IGM. This study assessed alterations in intracellular cytokine expression patterns in different T-lymphocyte subsets after ozone therapy in refractory IGM. Peripheral blood T lymphocyte subsets (CD8(+), CD4(+), CD4(+)CD25(+) CD127(-)) were analyzed via flow-cytometry for intracellular cytokine expressions IFN-gamma, TNF-alpha, IL-10, and TGF-beta before and after completion of 4-month systemic ozone therapy. Ozone therapy significantly increased the CD4(+)IFN-gamma(+) (p = 0.032), CD4(+)TNF-alpha(+) (p = 0.028), and the CD8(+) TNF-alpha(+) (p =0.012) T cells. In contrast, significant decreases in CD4(+) IL-10(+) (p = 0.047) and CD8(+)IL-10(+) T cells (p = 0.022) and CD4(+)CD25(+) CD127(-//low) Treg cells secreting TGF-beta (p = 0.005) were found after ozone therapy. When patients were analyzed according to the response to ozone therapy, patients with a complete remission were more likely to have increased CD3(-)CD16(+)CD56(+) natural killer cells (p = 0.0027) and decreased CD19(+)B lymphocytes (p = 0.046) following ozone therapy. Our results suggest that ozone therapy stimulated a T-helper-1 response associated with IFN-gamma production and downregulation of TGF-beta expression in CD4(+)CD25(+)CD127(-) Treg cells. These alterations in the immune system following ozone therapy can improve wound healing and restore immune dysfunction in patients with refractory IGM. Istanbul Breast Society

Objectives: This study aims to investigate the efficacy of abbreviated breast magnetic resonance imaging (MRI) in neoadjuvant chemotherapy (NAC) response evaluation. Methods: MR images of 50 locally advanced breast cancer patients who underwent standard protocol (SP) breast MRI before and after NAC were re-evaluated retrospectively. Abbreviated protocol (AP) was obtained by extracting images from SP and then evaluating them in a separate session. Protocols were compared with the histological findings after surgery as the reference standard. Results: A statistically significant difference was found between the two protocols in response evaluation by the McNemar test (p=0.018). However, the Kappa value was 0.62 (p Conclusion: Despite the statistical differences, there was a significant correlation in response evaluation between the two protocols. The pathological results were moderately correlated with both protocols, with SP slightly higher. However, the residual maximum median diameters were smaller than the pathology with both protocols. These results may limit the use of AP in evaluating the local extent of the tumor, especially in patients who will undergo breast-conserving surgery.

We assessed the feasibility of SPECT/CT lymphoscintigraphy ( 99m Tc-nanocolloid) method to simplify and improve targeted axillary dissection of clipped axillary lymph node (axLN) after neoadjuvant chemotherapy (NAC) in initially node-positive breast cancer.Fifteen patients who had clip placement to biopsy-confirmed axLN metastasis due to clinically node-positive breast cancer before NAC and underwent SPECT/CT lymphoscintigraphy for surgery after NAC were included into the study. SPECT/CT lymphoscintigraphy was performed to localize the clipped node and to assess if the clipped lymph node (LN) had 99m Tc-nanocolloid uptake or not. In case the clipped node had no uptake on SPECT/CT, the patient was referred to wire-guided localization procedure. Blue dye was also injected for dual mapping of sentinel LN biopsy.All patients had only ipsilateral axLN metastasis. SPECT/CT lymphoscintigraphy showed that clipped LNs were radioavid in 12 of 15 patients (80%). Clipped LNs were not blue-stained in 5 patients (33.3%), and in 2 of them, clipped LNs were radioavid in SPECT/CT. Wire-guided localization was required in only 3 patients (20%) for nonradioavid/blue-stained clipped LNs. Removal of the clipped nodes was confirmed in all cases with a success rate of 100% by specimen graphy.SPECT/CT lymphoscintigraphy seems feasible to determine the clipped LNs intraoperatively without requiring additional invasive methods in most of the patients. This technique simplifies and improves targeted axillary dissection of the clipped axLNs after NAC in initially node-positive breast cancer and can be adapted to clinical practice with further investigations.

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.

Background: Cold therapy is an important non-pharmacologic method used for pain relief. Aim: In the present study, we aimed to evaluate the therapeutic effect of cold therapy on managing postoperative pain following breast-conserving surgery (BCS) and assess its effect on recovering quality. Method: The study was planned and implemented as a randomized controlled clinical study. Sixty patients with breast cancer were included in this study. All patients underwent BCS at Istanbul Faculty of Medicine. There were 30 patients in both the cold therapy and control groups. In the cold therapy group, a cold pack was placed around the incision line for 15 minutes every hour from the first hour after the operation until the 24th hour. To all the patients in both groups, pain levels were measured by visual analog scale (VAS) at the postoperative 1st, 6th, 12th, and 24th hours, respectively, and the quality of recovery was evaluated by a Quality of Recovery-40 questionnaire at the postoperative 24th hour. Results: The patients' median age was 53 (range: 24-71). All patients were T1-2 clinically and had no lymph node metastasis. Interestingly, the mean of pain level in the cold therapy group was statistically significantly lower in the first 24 hours (1st, 6th, 12th, and 24th hours) of the postoperative period (p = .001). Notably, the cold therapy group had higher recovering quality than the control group. In the first 24 hours, only 4 (12.5%) patients in the cold therapy group received additional analgesics, whereas all patients (100%) in the control group received additional analgesics (p = .001). Conclusions: Cold therapy is an easy and effective non-pharmacologic method for pain relief after BCS in patients with breast cancer. Cold therapy reduces the acute pain of the breast and contributes to the quality of recovery of those patients.

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 analyse 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. Twenty-nine patients (58%) were detected to be positive for PD-L1 on both TCs and ICs, whereas 25 patients (50%) were positive for TC PD-L1 expression, and PD-L1 on ICs was detected (44%) in 23 patients. 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%, versus 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: Our results suggest that patients with a high TC PD-L1 expression were more likely to have a better outcome. Since patients with residual TCs expressing 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 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.

Background: Residual nodal disease at the completion axillary lymph node dissection (ALND) has been reported in over 60% in patients with a positive sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC). This study aimed to explore whether any clinical or histopathological characteristics of patients may be associated with a lower likelihood of having non-SLN metastasis at ALND. Methods: Between January 2004 to January 2021, 459 patients with cT1-4/N1-3 underwent ALND due to a positive SLNB after NAC. Demographic, clinical and histopathological characteristics of patients were analyzed to predict the non-SLN metastasis at ALND. Sentinel lymph node ratio was defined as the ratio of the number of positive SLN to the total excised SLNs. Results: Median age was 47 (21-84). Of those, the majority of the patients had cT1-2 (67.8%) and cN1 disease (78.1%), whereas 76.5% of tumors were invasive ductal carcinoma. The frequency of non-SLN metastases according to the tumor subtypes were 59.5% in luminal A, 73.8% in HER2(-) luminal B, 60.3% in HER2(+) luminal B, 66.7% in non-luminal HER2(+), and 66.7% in triple negative breast carcinoma. Of those with removal more than 2 SLNs, having 1 positive SLN, or breast pathologic complete response, or cT1-2 disease , or a SLN ratio FactorsOR(95%CI)p-valuecT0.009*1&20.45(0.25-0.82)3&4Reference (1)SLN Status0.006*ITC and micrometastasis0.24(0.09-0.65)MacrometastasisReference (1)SLN-Ratio (%) Citation Format: Neslihan Cabioglu, Hasan Karanlık, Abdullah Igci, Mahmut Muslumanoglu, Mustafa Tukenmez, Selman Emiroglu, Enver Ozkurt, Semen Onder, Pinar Saip, Yesim Eralp, Adnan Aydiner, Ekrem Yavuz, Vahit Ozmen. Factors predicting a lower likelihood of residual nodal disease in clinically-node positive patients undergoing sentinel node surgery after neoadjuvant chemotherapy for breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-07.

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.