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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.

High expression of immune checkpoint receptors (ICRs) in the tumor microenvironment regulates the anti-tumor response. In this study, the differential expressions of ICRs on tumor-infiltrating lymphocytes (TILs) in patients with early-stage breast cancer were investigated.The study included 32 patients who underwent surgery with a diagnosis of early-stage breast cancer between September 2018 and March 2020. TIL isolation was performed using a MACS tumor separation device and tumor separation kit. PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT expression of cytotoxic T and natural killer (NK) cells on TILs and peripheral blood lymphocytes (PBLs) were determined by flow cytometry.Patients with a high Ki-67 index, high TIL density, and HER-2 positivity were more likely to have increased CD16+CD56dim NK cells on TILs. Patients with T2 tumors were more likely to have increased expression of PD-1, LAG-3, and TIGIT on tumor-infiltrating CD8+ cytotoxic T cells than those with T1 tumors. PD-1, CTLA-4, TIGIT, LAG-3, and TIM-3 expression of CD8+ T and CD16-CD56bright NK cells in TILs showed significant positive correlations with each other. PD1+CD8+, TIGIT+CD16+, and CTLA-4+CD56+ cells in PBLs and TILs were found to be negatively correlated, whereas only TIM-3+ expression of CD8+ T and CD16+CD56dim cells in PBLs and TILs showed positive correlations.Our results suggest that CD16+CD56dim NK cells on TILs may play a major role in the immune response against HER2-positive or highly proliferating breast tumors in patients with early-stage breast cancer. Furthermore, various ICRs were found to be highly co-expressed with each other on TILs, including PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT. These receptors may synergistically suppress the response to the tumor, which may trigger immune escape mechanisms in the early stage of carcinogenesis. However, ICR expressions other than TIM3 on PBLs were not found to accompany their counterparts on TILs.

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.

Background Recent studies have shown a lower likelihood of locoregional recurrences in patients with a low 21-gene recurrence score (RS). In this single-institution study, we investigated whether there are any associations between different cutoff values of 21-gene RS, histopathological factors, and outcome in patients with long-term follow-up. Methods The study included 61 patients who had early-stage (I-II) clinically node-negative hormone receptor-positive and HER2-negative breast cancer and were tested with the 21-gene RS assay between February 2010 and February 2013. Demographic, clinicopathological, treatment, and outcome characteristics were analyzed. Results The median age was 48 years (range, 29–72 years). Patients with high histologic grade (HG), Ki-67 ≥ 25%, or Ki-67 ≥ 30% were more likely to have intermediate/high RS (≥ 18). Based on the 21-gene RS assay, only 19 patients (31%) received adjuvant chemotherapy. At a median follow-up of 112 months, 3 patients developed locoregional recurrences (4.9%), which were treated with endocrine therapy alone. Among patients treated with endocrine treatment alone (n = 42), the following clinicopathological characteristics were not found to be significantly associated with 10-year locoregional recurrence free survival (LRRFS): age 11. However, patients with RS ≥ 16 had significantly poorer 10-year LRRFS compared to those with RS p = 0.039). Conclusions The results suggest that patients with clinically node-negative disease and RS ≥ 16 are more likely to benefit from adjuvant chemotherapies. However, those with RS

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 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.

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.

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.

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.

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

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.

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

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

Breast cancers in Turkey tend to be diagnosed at advanced stages due to lack of organized comprehensive mammographic screening. In this study factors associated with having a mammogram among healthy women of screening age in Bahcesehir county a region in Istanbul were investigated to assess the feasibility of organized breast cancer screening in Turkey. In this cross-sectional study 659 healthy women aged between 40 and 69 years were surveyed. A multiple-choice questionnaire was used to obtain information regarding patient demographics family history of cancer and patient knowledge on mammographic screening. Factors associated with increased likelihood of having a mammogram included age older than 50 (OR = 1.75; 95% CI = 1.23-2.49) higher educational level (high school or university graduate; OR = 1.55; 95% CI = 1.07-2.25) and undergoing periodic gynecologic examinations (OR = 5.53; 95% CI = 3.88-7.89). Women aged between 40 and 49 years who were most likely to have a mammogram within the last 2 years were characterized by a higher educational level (OR = 1.94; 95% CI = 1.14-3.31) periodic gynecologic examinations (OR = 4.06; 95% CI = 2.53-6.51) and a first or second degree family history of breast cancer (OR = 2.2; 95% CI = 1.06-4.50). In contrast women aged between 50 and 69 years were more likely to have undergone mammography within the previous 2 years if they also had undergone periodic gynecologic examinations (OR = 8.63; 5.04-14.77). Our findings suggest that women of lower educational level and those who do not undergo routine wellness visits with their gynecologist will need to be specifically targeted for educational outreach to achieve broad screening compliance within the population.

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

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

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

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

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

Positive/close margins are associated with higher in-breast failure rates after breast-conserving surgery (BCS). We investigated whether intraoperative margin assessment aids in obtaining negative margins, and to evaluate the local control thus achieved.Between 1994 and 1996, 264 patients underwent BCS for stages 0-III breast cancer [invasive, n = 200; ductal carcinoma in situ (DCIS), n = 64]. Intraoperative margin assessment included gross tissue inspection, specimen radiography, with or without frozen section.Ninety-two patients (46%) with invasive cancer and 24 (38%) with DCIS had positive/close margins on the permanent section analysis of their initial surgical specimens. Fifty-eight patients (29%) with invasive cancer and six (9%) with DCIS had initial positive/close margins, and were rendered margin-negative by intraoperative analysis and immediate re-excision. Final margins on permanent pathology were positive/close in 52 patients (20%): 34 patients (17%) with invasive cancer and 18 patients (28%) with DCIS. By multivariate analysis, excisional biopsy for diagnosis, larger tumor size, and multifocality were associated with final positive/close margins. Of these 52 patients, 23 underwent a second operation to achieve widely negative margins (13 completion mastectomies, 10 re-excisions). The 5-year ipsilateral breast recurrence-free survival rates after BCS and radiation were 99% for invasive cancer (n = 167) and 100% for DCIS (n = 27).Intraoperative assessment of margins assisted in identifying positive/close margins and allowed over a quarter of the patients to be rendered margin-negative with intraoperative re-excision at their original operation. This approach resulted in excellent local control in patients treated with BCS and radiation.

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

Experimental evidence suggests that CXCR4, a Gi protein–coupled receptor for the ligand CXCL12/stromal cell–derived factor-1α (SDF-1α), plays a role in breast cancer metastasis. Transactivation of HER2-neu by G protein–coupled receptor activation has been reported as a ligand-independent mechanism of activating tyrosine kinase receptors. We found that SDF-1α transactivated HER2-neu in the breast cancer cell lines MDA-MB-361 and SKBR3, which express both CXCR4 and HER2-neu. AMD3100, a CXCR4 inhibitor, PKI 166, an epidermal growth factor receptor/HER2-neu tyrosine kinase inhibitor, and PP2, a Src kinase inhibitor, each blocked SDF-1α–induced HER2-neu phosphorylation. Blocking Src kinase, with PP2 or using a kinase-inactive Src construct, and inhibiting epidermal growth factor receptor/HER2-neu signaling with PKI 166 each inhibited SDF-1α–stimulated cell migration. We report a novel mechanism of HER2-neu transactivation through SDF-1α stimulation of CXCR4 that involves Src kinase activation.

Interactions between the CXCR4 chemokine receptor in breast cancer cells and the ligand CXCL12/SDF-1alpha are thought to play an important role in breast cancer metastases. In this pilot study, CXCR4 expression along with other biomarkers including HER2-neu and EGFR, were measured in primary tumor samples of patients with operable breast cancer to test whether any of these biomarkers alone and in combination could indicate breast cancer with high likelihood of metastasizing to bone marrow. Cytokeratin (CK) positive cells in bone marrow were identified by flow-cytometry following enrichment with CK 7/8 antibody-coupled magnetic beads. Primary tumors (n = 18) were stained with specific antibodies for CXCR4, HER2-neu, EGFR, and PCNA using an indirect avidin-biotin horseradish peroxidase method. The majority of the patients had T2/T3 tumors (72%), or lymph node involvement (67%) as pathologic characteristics that were more indicative of high-risk breast cancer. High CXCR4 cytoplasmic expression was found in 7 of 18 patients (39%), whereas 6 of 18 patients (33%) were found to have CK positivity in bone marrow. The median number of CK(+) cells was 236 (range, 20-847) per 5 x 10(4) enriched BM cells. The presence of CK(+) cells in bone marrow was found to be associated with increased expression of CXCR4 alone or in addition to EGFR and/or HER2-neu expression (P = 0.013, P = 0.005, and P = 0.025, respectively) in primary tumors. Furthermore, three patients with high CK positivity (236 CK(+) per 5 x 10(4) enriched bone marrow cells) in bone marrow exclusively expressed high levels of CXCR4 with EGFR/HER2-neu (P = 0.001). Our data suggest that high CXCR4 expression in breast cancer may be a potential marker in predicting isolated tumor cells in bone marrow. CXCR4 coexpression with EGFR/HER2-neu might further predict a particular subset of patients with high CK positivity in bone marrow.

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