Objective: Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast condition lacking standardized treatment and with unpredictable outcomes. To address these issues, using clinical and ultrasound findings from an initial subset, we created the Pittsburgh Classification to stratify severity and developed a corresponding treatment algorithm for IGM, then evaluated its effectiveness in a larger cohort of IGM patients. Materials and Methods: This retrospective multicenter study reviewed clinical and sonographic findings and outcomes of women with biopsy-proven IGM treated at multiple breast centers between 2020 and 2025. The Pittsburgh clinical classification ranges from Type 1 (minimal skin irritation) to Type 5 (widespread involvement); ultrasound classification spans Type A (localized mass ≤2 cm) to Type D (diffuse disease). Treatments were assessed utilizing the Pittsburgh algorithm, with responses classified as full response (CR), near-complete response (nCR), or no response (NR). Chi-square tests assessed associations (p<0.05). Results: Of 522 patients included (mean age 37.0±8.8 years), 86.4% (n = 451) received algorithm-concordant treatment, achieving CR in 68.7% (n = 310), nCR in 35.3% (n = 159) and NR in 11.8% (n = 53). Among these, 65.4% (295/451) of patients with CR were concordant with the Pittsburgh treatment algorithm, whereas 13.6% (n = 71) patients received discordant treatments, with a significantly lower CR rate of 21.1% (15/71) (p<0.001). Multifocal disease was significantly more prevalent in NR (83.0%, 44/53) and nCR (70.4%; 112/159) patients compared to CR (20.6%; 64/310) (p<0.001), although lesion-based response rates were similar (CR 56.8%, nCR 57.0%, NR 56.6%). Regarding concordance with treatment algorithm, clinical Type 4 IGM was more prevalent in NR (67.9%; 36/53) and nCR (72.9%, 116/159), whereas in clinical Type 1 IGM, NR, nCR, and CR were 1.8% (1/53), 4.4% (7/159), and 30.6% (95/310), respectively (p<0.001). Surgery at presentation was preferred in 16.9% (n = 88) of patients, with 6% (n = 30) requiring subsequent surgical treatments to treat residual disease. Conclusion: Concordance with the proposed IGM treatment algorithm based on clinical and ultrasound findings resulted in significantly higher CR rates. Multiple foci and stratified clinical types correlated with outcomes. Prospective global research is needed to validate these findings.

De novo metastatic breast cancer (dnMBC) accounts for 3-10% of newly diagnosed cases, with 20-40% presenting as a bone-only metastatic disease, which can achieve survival outcomes exceeding 10 years with multimodal therapy. However, the role of multimodal therapy remains controversial in the guidelines. Objective: This study aims to identify dnBOMBC subgroups to develop a pragmatic staging system for guiding locoregional therapy decisions. Materials and Methods: Data from the MF07-01 phase III randomized trial (2021, median follow-up time (mFT): 40 months (range 1-131)) and the BOMET prospective multi-institutional registry trial (2021, mFT: 34 months (range 25-45)) were combined for analysis, including only patients who presented with bone-only metastases. Exclusion criteria were patients under 18 and those with a history of prior cancer or cancer metastases. Patients with missing data and positive surgical margins were excluded. Out of 770 patients, 589 were included. Survival analyses were first conducted according to molecular subgroups, after which patients were further stratified by hormone receptor status, human epidermal human epidermal growth factor receptor 2 (HER2) status, tumor grade, and clinical T (cT) stage. Group A (GrA) included hormone receptor (HR)-positive, low- or intermediate-grade tumors at any cT; HR-positive, high-grade tumors with cT0-3; or any HER2-positive tumors. Group B (GrB) included HR-positive, high-grade tumors with cT4 disease or any triple-negative (TN) tumors. Results: The hazard of death (HoD) was 43% lower in GrA than in GrB. Median OS was 65 months (39-104) for GrA patients and 44 months (28-72) for GrB patients (HR 0.57, 95% CI 0.41-0.78, p = 0.0003). Primary tumor surgery (PTS) significantly improved OS in GrA patients, regardless of the number of metastases (solitary: HR, 0.375, 95% CI 0.259-0.543, p < 0.001; multiple: HR 0.435, 95% CI 0.334-0.615, p < 0.001). Conversely, GrB patients did not experience a significant benefit from PTS. Conclusions: This study demonstrates that GrA patients have better OS than GrB patients, and PTS reduces the HoD in GrA patients compared to systemic therapy alone. These findings support using a modified staging system in dnBOBMC to identify patients who may benefit from multimodal therapy including PTS.

ImportanceIncreasing evidence supports the oncologic safety of de-escalating axillary surgery for patients with breast cancer after neoadjuvant chemotherapy (NAC).ObjectiveTo evaluate the oncologic outcomes of de-escalating axillary surgery among patients with clinically node (cN)–positive breast cancer and patients whose disease became cN negative after NAC (ycN negative).Design, Setting, and ParticipantsIn the NEOSENTITURK MF-1803 prospective cohort registry trial, patients from 37 centers with cT1-4N1-3M0 disease treated with sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) alone or with ypN-negative or ypN-positive disease after NAC were recruited between February 15, 2019, and January 1, 2023, and evaluated.ExposureTreatment with SLNB or TAD after NAC.Main Outcomes and MeasuresThe primary aim of the study was axillary, locoregional, or distant recurrence rates; disease-free survival; and disease-specific survival. Number of axillary lymph nodes removed was also evaluated.ResultsA total of 976 patients (median age, 46 years [range, 21-80 years]) with cT1-4N1-3M0 disease underwent SLNB (n = 620) or TAD alone (n = 356). Most of the cohort had a mapping procedure with blue dye alone (645 [66.1%]) with (n = 177) or without (n = 468) TAD. Overall, no difference was found between patients treated with TAD and patients treated with SLNB in the median number of total lymph nodes removed (TAD, 4 [3-6] vs SLNB, 4 [3-6]; P = .09). Among patients with ypN-positive disease, those who underwent TAD were more likely to have a lower median lymph node ratio (TAD, 0.28 [IQR, 0.20-0.40] vs SLNB, 0.33 [IQR, 0.20-0.50]; P = .03). At a median follow-up of 39 months (IQR, 29-48 months), no significant difference was found in the rates of ipsilateral axillary recurrence (0.3% [1 of 356] vs 0.3% [2 of 620]; P ≥ .99) or locoregional recurrence (0.6% [2 of 356] vs 1.1% [7 of 620]; P = .50) between the TAD and SLNB groups, with an overall locoregional recurrence rate of 0.9% (9 of 976). The initial clinical tumor stage, pathologic complete response, and use of blue dye alone as a mapping procedure were not associated with the outcome. Even though patients with TAD demonstrated an increased disease-free survival rate compared with the SLNB group, this difference did not reach statistical significance (94.9% vs 92.6%; P = .07). Factors associated with decreased 5-year disease-specific survival were cN2-3 axillary stage (cN1, 98.7% vs cN2-3, 96.8%; P = .03) and nonluminal type tumor pathologic characteristics (luminal, 98.9% vs nonluminal, 96.9%; P = .007).Conclusions and RelevanceThe short-term results suggest very low rates of axillary and locoregional recurrence in a select group of patients with cN-negative disease after NAC treated with TAD alone or SLNB alone followed by regional nodal irradiation regardless of the SLNB technique or nodal pathology. Whether TAD might provide a clear survival advantage compared with SLNB remains to be proven in studies with longer follow-up.

Introduction: The impact of locoregional treatment (LRT) on survival in de novo bone-only metastatic breast cancer (dnBOMBC) is controversial. This study aims to assess the effect of LRT on survival, utilizing international, prospectively acquired data in this cohort of patients. Materials and Methods: Patients with dnBOMBC were divided into two groups: those receiving systemic therapy only (ST) and those undergoing LRT. Further, patients who received LRT were divided into two subgroups: those who received ST after LRT (LRT+ST group) and those who received ST prior to LRT (ST+LRT group). Factors associated with disease progression, including solitary or multiple bone metastases, were analyzed. Results: There was a total of 744 patients with dnBOMBC treated at each of the participating institutions between 2014 and 2022, with 372 (50%) participants in each arm. Median follow-up was 48 months (32–66, 25–75%). Patients in the LRT group were significantly younger than the ST group [50 (42, 60) vs. 55 (44, 66), p = 0.0001]. There were no significant differences in grade, HER2 status, triple-negative status, receipt of hormonal therapy, or intervention to metastatic sites. During follow-up, 58% (n = 217) of patients in the ST group and 32% (n = 120) of patients in the LRT group died (p < 0.001). Local progression was observed in 20% of the patients in the ST group, whereas 9% progressed in the LRT group (p = 0.0001). Systemic progression occurred more in the ST group; 66% (n = 244) compared to 41% (n = 152) of patients in the LRT group (p < 0.001). The hazard of death was 64% lower in the LRT group than in the ST group (HR: 0.36, 95% CI: 0.29–0.45, p < 0.0001). The burden of metastatic disease differed significantly between the two groups, with a higher rate of solitary bone metastases in the LRT group compared to the ST group (50% vs. 24%, p < 0.001). However, the LRT group had better overall survival (OS) for both solitary (HR: 0.38, 95% Cl: 0.26–0.55) and multiple (HR: 0.38, 95% Cl: 0.29–0.51) bone metastasis patients. Within the LRT group, survival rates were similar whether the breast surgery was performed before or after ST. Multivariate Cox analysis showed that LRT and ER/PR positivity significantly decrease the hazard of death (p < 0.05). Conclusions: Analysis of this large multi-institutional patient cohort provides further evidence that LRT is associated with longer OS and lower locoregional recurrence rates in patients with dnBOMBC. In breast cancer patients with bone-only metastases at presentation, the decision for LRT should be made through a multidisciplinary approach with consideration of surgical therapy at the primary tumor.

BACKGROUND:This study aims to identify factors predicting recurrence and unfavorable prognosis in cN+ patients who have undergone sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy (NAC). METHODS:The retrospective multi-centre "MF18-02" and the prospective multi-centre cohort registry trial "MF18-03" (NCT04250129) included patients with cT1-4N1-3M0 with SLNB+/- axillary lymph node dissection (ALND) post-NAC. RESULTS:A total of 2407 cN+ patients, who later achieved cN0 status after NAC and subsequently underwent SLNB, were studied. The majority had cT1-2 (79.1%) and N1 (80.7%). After a median follow-up time of 41 months, the rates of locoregional recurrence and axillary recurrence (AR) were 1.83% and 0.37%, respectively. No significant difference in locoregional recurrence or AR rates was observed between the SLNB/targeted axillary dissection-only (n = 1470) and ALND (n = 937) groups. Factors significantly linked with AR included age younger than 45 years, nonpathological complete response (non-pCR) in the breast, and nonluminal pathology. Locoregional recurrences were associated with nonluminal or HER2(+) pathology, non-pCR in the breast, and ALND. Poor prognostic factors for disease-free survival (DFS) included having cT3-T4, no breast pCR (non-pCR), ypN(+), and nonluminal pathology. No significant difference was found in DFS or disease-specific survival (DSS) rates among ypN0, ypN-isolated tumour cells, ypNmic, and ypN1. However, significant decreases in DFS and DSS rates were observed when comparing ypN2 or ypN3 disease with ypN0. CONCLUSIONS:The present large registry data indicate that younger patients (<45), those with nonluminal pathology, and those who only partially respond in the breast are more susceptible to axillary and locoregional recurrences.

OBJECTIVE:The role of younger age as a prognostic factor in breast cancer remains debated. Despite its association with an aggressive clinical course, there is insufficient research on its etiology. This study aimed to analyze age-related differences in breast cancer diagnosis among Turkish women. MATERIALS AND METHODS:Data from 23,594 patients in the National Breast Cancer Database (NBCD) were analyzed. The demographic, clinical, and pathological characteristics of patients aged ≤40 years were compared with those >40 years. RESULTS:The median age was 50 years (range 18-97). Among them, 4,535 patients (19%) were 40 years old or younger, with 84% of this subgroup being over 30 years old. Conversely, 19,059 patients (81%) were older than 40. Patients in the younger age group were less likely to have pathologic T1 disease (41% vs. 47%), N0 disease (49% vs. 55%), and Stage I disease (25% vs. 31%) compared to those over 40 (p<0.001). The rates of mastectomy (41% vs. 39%; p = 0.024) and axillary dissection (71% vs. 65%; p = 0.001) were higher among patients diagnosed at 40 years of age or younger. Multivariate analysis identified significant associations in younger patients, including invasive ductal carcinoma (95% CI, 1.06-1.43), estrogen receptor (ER) negativity (95% CI, 1.26-1.87), PR negativity (95% CI, 1.21-1.75), high histologic grade (95% CI, 1.43-1.87), multifocality/multicentricity (95% CI, 1.26-1.72), T3-T4 tumors (95% CI, 1.06-1.66), and axillary positivity (95% CI, 1.025-1.321). CONCLUSIONS:Breast cancer diagnosed at ≤40 years is more likely to exhibit aggressive biology, multifocality, or multicentricity presentation, and present at advanced stages. Consequently, younger patients experience higher rates of mastectomy and axillary dissection. These findings suggest a poorer prognosis, highlighting the need for more intensive therapeutic strategies in this population.

Abstract Background: Previous prospective studies reported decreased false negative rates in patients presenting with T1-3/cN1 disease, with the removal of 2 or more sentinel lymph nodes (SLNs), using combined technique for SLN biopsy (SLNB), and by targeted axillary dissection (TAD) in initially clinically node-positive patients after neoadjuvant chemotherapy (NAC). The aim of this prospective study is to compare the feasibility and the oncological safety of TAD with SLNB in patients with cN-positive/ycN0 breast cancer following NAC in a prospective study. Methods: This study included patients with a cT1-4N1-3M0 disease from the prospective multicenter MF1803 NEOSENTITURK registry study who were treated either SLNB- or TAD-alone without ALND. TAD included removing the biopsy-proven positive LN marked mostly with a clip as SLN or non-SLN. All patients had nodal and regional irradiation. Results: Between 2019 to 2021, 976 patients with cT1-4N1-3M0 disease from 37 centers underwent either SLNB-alone (n=620) or TAD-alone (n=356). Patients with TAD (median age: 46, range: 24-76) and SLNB (median age:46, range: 21-80) have shown a similar age distribution. The median number (range, 25%-75%) of SLNs and total LNs and total metastatic LNs removed were 3 (2-4), 4(3-6), and 1 (1-2), respectively. Patients with TAD were more likely to have cT1-2 disease (91.9% vs 78.7%, p< 0.001), cN1 disease (85.7% vs 78.5%, p< 0.006), a breast conservative surgery (66.0% vs 51.3%, p< 0.001), the combined technique for mapping (44.1% vs 22.3%, p< 0.0001), and a decreased median (IQR) lymph node ratio as calculated by the total positive lymph node number to the total lymph node number (0.29:0.20-0.40 vs 0.33: 0.20-0.50; p=0.033). Of note, there was a trend for the decreased non-sentinel lymph node positivity in the TAD-group compared to the SLNB-group that did not reach the statistical significance (TAD: 10% vs SLNB: 19%, p=0.07). However, no significant difference could be found in pathological characteristics including tumor type, breast pCR, non-luminal disease such as HER2-positivity or triple negative disease or presence of low volume metastatic disease (ITC or micrometastasis), and extracapsular extension (Table 1). Of note, patients with ypN-positive disease (n=351) were more likely to have SLNs (ypN+, 3.7±1.7 vs ypN0, 3.4±1.7, p=0.008) or total LNs (ypN+, 4.7±1.9 vs ypN0, 3.4±1.9, p=0.001) removed compared to those with ypN0 (n=635). Among those with ypN0 disease, patients with TAD were more likely to have LNs removed compared to those with SLNB (TAD, 4.2±1.9 vs 3.9±1.9, p=0.034) (Table 2). Of those with ypN+, patients with TAD were more likely to have SLNs compared to those with SLNB (TAD, 3.9±1.7 vs 3.5±1.7, p=0.062), whereas patients with SLNB were more likely to have non-SLNs removed compared to those with TAD (TAD, 2.3±1.4 vs 2.9±1.5, p=0.028). At a mean follow-up of 28.8 months (±12.1), the ipsilateral axillary and locoregional recurrence rates were 0.2% (n=2) and 0.4% (n=4) in the TAD-group and SLNB_group, respectively. Of note, no significant difference could be found in ipsilateral axillary, locoregional, and systemic recurrences between cohorts treated with TAD-alone vs SLNB-alone (Table 3). Conclusion: Our findings suggest that TAD might be more feasible in ypN+ patients which resulted in a decreased lymph node ratio and decreased non-SLN positivity. In ypN0 patients, TAD may contrary cause unnecessary lymph node removal that might be important in arm function and lymphedema development. Furthermore, our findings with short-term follow-up indicate that axillary and locoregional recurrences were observed at very low rates in a selected group of ycN0 patients treated with SLN- or TAD without ALND. Therefore, omission of ALND could be safely considered for patients with limited nodal involvement ( <2 LNs) as long as <3 LNs removed and nodal radiotherapy provided. Table 1. Clinicopathologic Characteristics According to the Axillary Surgery: Targeted Axillary Dissection (=TAD) versus Sentinel Lymph Node Biopsy (=SLNB) Table 2. Clinicopathologic Characteristics According to the Pathological Nodal Status Table 3. Locoregional and systemic recurrences in cT1-4N1-3 patients treated with Targeted Axillary Dissection (=TAD) or Sentinel Lymph Node Biopsy (=SLNB) (Nf976) Citation Format: Neslihan Cabıoğlu, Hasan Karanlik, Mehmet Ali Gulcelik, Havva Belma Kocer, Mahmut Muslumanoglu, Abdullah İgci, Mustafa Tukenmez, Cihan Uras, Enver Ozkurt, Gokhan Giray Akgul, Selman Emiroglu, Süleyman Bademler, Ahmet Dağ, Didem Can Trabulus, Nilufer Yıldirim, Guldeniz Karadeniz Cakmak, Ebru Sen Oran, Halil Kara, Gul Basaran, Ayse Altinok, M. Umit Ugurlu, Kazim Senol, Baha Zengel, Niyazi Karaman, Ecenur Varol, Ece Dilege, Yasemin Bolukbasi, Alper Akcan, Yeliz Emine Ersoy, Aykut Soyder, Serdar Ozbas, Mehmet Velidedeoglu, Beyza Ozcinar, N. Zafer Utkan, Bulent Citgez, Burak Celik, Leyla Zer, Gurhan Sakman, Levent Yeniay, Lutfi Dogan, Mutlu Dogan, Fazilet Erozgen, BERK GOKTEPE, Orhan Agcaoglu, Taner Kivilcim, Fatih Levent Balci, Bahadir M. Gulluoglu, Ayfer Kamali Polat, Kamuran Ibis, Vahit Ozmen. Feasibility and oncological safety of targeted axillary dissection or sentinel lymph node biopsy in patients with clinically node-positive disease after neoadjuvant chemotherapy in the prospective MF-1803 NEOSENTITURK-study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS01-01.

BackgroundThe omission of axillary lymph node dissection (ALND) remains controversial for patients with residual axillary disease after neoadjuvant chemotherapy (NAC), regardless of the residual burden. This study evaluated the oncologic safety and factors associated with outcomes in patients with residual axillary disease. These patients were treated solely with sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD), without ALND, after NAC.MethodsA joint analysis of two different multicenter cohorts-the retrospective cohort registry MF18-02 and the prospective observational cohort registry MF18-03 (NCT04250129)-was conducted between January 2004 and August 2022. All patients received regional nodal irradiation.ResultsFive hundred and one patients with cT1-4, N1-3M0 disease who achieved a complete clinical response to NAC underwent either SLNB alone (n = 353) or TAD alone (n = 148). At a median follow-up of 42 months, axillary and locoregional recurrence rates were 0.4% (n = 2) and 0.8% (n = 4). No significant difference was found in disease-free survival (DFS) and disease-specific survival (DSS) rates between patients undergoing TAD alone versus SLNB alone, those with breast positive versus negative pathologic complete response, SLN methodology, total metastatic LN of one versus >= 2, or metastasis types as isolated tumor cells with micrometastases versus macrometastases. In the multivariate analysis, patients with nonluminal pathology were more likely to have a worse DFS and DSS, respectively, without an increased axillary recurrence.ConclusionsThe omission of ALND can be safely considered for patients who achieve a complete clinical response after NAC, even if residual disease is detected by pathologic examination. Provided that adjuvant radiotherapy is administered, neither the SLNB method nor the number of excised LNs significantly affects oncologic outcomes.

Abstract Introduction: The impact of loco-regional treatment (LRT) on survival in de novo bone-only metastatic breast cancer (BC) is controversial. The aim of this study is to assess the effect of LRT on survival utilizing international, prospectively acquired data in this cohort of patients. Materials and Methods: Patients with de novo metastatic BC with bone-only metastases were divided into two groups: those receiving systemic therapy only (ST) and those undergoing LRT. Patients who received LRT were divided into two groups: those who received ST after LRT (LRT+ST arm) and those who received ST prior to LRT (ST+LRT arm). Solitary or multiple bone metastases were classified, and factors associated with disease progression were analyzed. Results: There were a total of 744 patients with de novo bone-only metastatic BC treated at each of the participating institutions between 2014 and 2022, with 372 (50%) participants in each arm. Median follow-up was 48 months (32-66, 25-75%). Patients in the LRT group were significantly younger than the ST group [50 (42, 60) vs 55 (44, 66), p=0.0001]. There were no significant differences in grade, Her2 neu and triple negative status, receipt of hormonal therapy and intervention to metastatic sites. During follow-up, 58% (n=217) of patients in ST arm and 32% (n=120) of patients in LRT arm died (p< 0.001). Local progression was observed in 20% of the patients in the ST arm whereas it was 9% in the LRT arm (p=0.0001). Systemic progression occurred more in ST arm; 66% (n=244) compared to 41% (n=152) of patients in LRT group (p< 0.001). The Hazard of death was 64% lower in LRT group than in ST group (HR: 0.36, 95% CI: 0.29-0.45), p<0.0001). The burden of metastatic disease was significantly different between groups with the solitary bone metastasis rate higher in LRT group than the ST only group (50% vs 24%, p< 0.001). However, the LRT group had better overall survival for both solitary (HR: 0.38, 95% Cl: 0.26-0.55) and multiple (HR: 0.38, 95% Cl: 0.29-0.51) bone metastases patients. Within the LRT group, survival rates were similar whether the breast surgery was performed before or after ST.Multivariate Cox analysis showed that LRT and ER/PR positivity significantly decrease the hazard of death (p< 0.05). Conclusion: Analysis of this large multi-institutional patient cohort provides further evidence that LRT improves overall survival and lowers loco-regional recurrence in patients with de novo bone-only metastatic BC. In breast cancer patients with bone-only metastases at presentation, the decision for LRT should be made through a multidisciplinary approach with consideration of surgical therapy at the primary tumor. Citation Format: Atilla Soran, Serdar Ozbas, Lutfi Dogan, Didem Can Trabulus, Jamila Alazhri, Kazim Senol, Berk Goktepe, Shruti Zaveri, Salyna Meas, Umut Demirci, Hasan Karanlik, Aykut Soyder, Ahmet Dağ, Ahmet Bilici, Mutlu Dogan, Mehmet Ali Nahit Sendur, Hande Koksal, Mehmet Ali Gulcelik, Neslihan Cabıoğlu, Levent Yeniay, N. Zafer Utkan, Nuri Karadurmus, Gul Daglar, Turgay Simsek, Birol Yildiz, Cihan Uras, Mustafa Tukenmez, Cihangir Ozaslan, Niyazi Karaman, Arda Isik, Berkay Demirors, Efe Sezgin, Vahit Ozmen, Anthony Lucci. Loco-regional Treatment in De Novo Bone Only Metastatic Breast Cancer; Prospective, Multi-Institutional Real-World Data, BOMETIN, Protocol MF14-1a [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-12.

Approximately 6-10% of all breast carcinoma is metastatic at diagnosis, termed de novo metastatic breast carcinoma (dnMBC). Systemic therapy remains the first line of treatment in dnMBC, but there is growing evidence that adjuvant locoregional treatment (LRT) of the primary tumor increases progression-free and overall survival (OS). Although selection bias may exist, real-world data from nearly half a million patients show that patients are undergoing primary tumor removal because of the survival benefit. The main question for the advocates for LRT in this patient population is not whether primary surgery is beneficial in dnMBC patients, but rather who is a good candidate for it. Oligometastatic disease (OMD) is a distinct subset of dnMBC that affects a limited number of organs. A better OS can be achieved with LRT in breast cancer patients, especially in those with OMD, bone only, or favorable subtypes. Though there is currently no consensus among breast care specialists on how to treat dnMBC patients, primary surgery for dnMBC should be taken into consideration for a subset of patients following an extensive multidisciplinary discussion.

Background Five to eight percent of breast cancer (BC) patients present with distant metastasis at diagnosis, known as ‘de Novo’ metastatic breast cancer (dnMBC). Recent data showed that approximately 40% of dnMBC patients undergo locoregional treatment (LRT). LRT treatment modalities for metastasis and primary tumor benefit a subset of patients with oligometastatic disease. Our study group has recently demonstrated two prospective studies regarding this topic with favorable outcomes. MF07-01 IMET study, one of the first clinical randomized trials, showed that the patients with the diagnosis of dnMBC undergoing LRT followed by systemic therapy had an additional 14% OS benefit by the end of the 10-year follow-up when compared with others who received only systemic therapy. A prospective multicenter registry study MF14-01 BOMET also presented LRT prolonged survival and decreased locoregional recurrence in a prospective registry study with a median follow-up of 3 years. Timing of primary breast surgery either at diagnosis or after systemic treatment provided a survival benefit similar to systemic therapy alone in bone-only dnMBC patients. Although, the optimal timing of concurrent endocrine therapy, radiotherapy, and/or sequential surgery remains unclear. Hypothesis We hypothesize that in the era of modern radiotherapy and endocrine therapy, concurrent radiation and endocrine therapy will be non-inferior to sequential treatment modalities in terms of locoregional and systemic disease control in dnMBC. ER/PR (+), Her2 neu (-) oligometastatic dnMBC patients are potentially curable with multimodality treatments. Objectives The primary objective is to perform a Phase I study to evaluate the feasibility of this curative intent treatment approach for patients with oligometastatic disease. Secondary objectives are to present the treatment response evaluating with CTC and/or ctDNA, and IHC and marker changes with multimodality treatments Methods Postmenopausal ER/PR (+) and Her2 neu (-), oligometastatic dnMBC patients will be enrolled in the study. Inclusion criteria: Primary breast tumor amenable for complete surgical resection, patients in good physical condition for receiving protocol-driven locoregional and systemic treatments and radiotherapy; Bone-only oligometastatic disease (5 or less metastasis); Primary tumor biopsy, metastatic site biopsy (ER/PR, Her2, Ki67). Exclusion criteria: Primary tumor not amenable for complete resection; primary tumor with extended infection, bleeding, or necrosis; patients with poor physical condition which prevents the patient from receiving protocol-driven locoregional and systemic treatment; synchronous primary cancer at the contralateral breast; clinically involved contralateral axillary nodes; patients not suitable for adequate follow-up, and failure to give informed consent. Study Design: • RT to the primary tumor (Hypo fractionated) + AI concurrent, Collect CTC and/or ctDNA • Add CDK4/6i to AI 2-4 weeks after RT + (6 months) • RT to bone metastasis (if still visible), Collect CTC and/or ctDNA + (12 months) • Primary Breast Surgery, Collect CTC and/orctDNA, ER/PR/Her 2 in the final specimen + • CDK4/6i +AI until progression and/or unmanageable toxicity Conclusion We hypothesize that in the era of modern radiotherapy and endocrine therapy, concurrent radiation and endocrine therapy will be non-inferior to sequential treatment modalities in terms of locoregional and systemic disease control in dnMBC. ER/PR (+), Her2 neu (-) oligometastatic dnMBC patients are potentially curable with multimodality treatments. Citation Format: Atilla Soran, Serdar Ozbas, Lutfi Dogan, Kamuran İbis, Mutlu Dogan, M Selam, Kazim Senol, Secil Ak Aksoy, Mine Ozsen, Sibel Cetintas, Turkkan Evrensel, Efe Sezgin. Preoperative radiotherapy and systemic therapy following surgery in ‘de novo’ metastatic breast cancer (Protocol MF22-01; Intervention Systemic Treatment METastasis-ISTMET) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-21-01.

INTRODUCTION Approximately one-fourth of patients presenting with early-stage breast cancer develop distant metastatic disease, a prominent cause of mortality. The role of metastasis-directed intervention is still uncertain in this cohort. The aim of this study is to evaluate whether intervention to metastatic lesions impacts overall survival (OS) and post-distant recurrence survival (PDRS), defined as survival after first occurrence of metastatic disease. METHODS Our prospectively maintained international multi-center database of patients diagnosed with distant recurrence was retrospectively reviewed. Patients initially presenting with stage I-III breast cancer and diagnosed with metastatic disease to the bone, liver or lung from 2014-2020 were divided into cohorts receiving intervention to their metastases (IM, n=180) versus no interventions to their metastases (NI, n=120). The characteristics of the patients were compared with X2 test. OS curves were calculated by Kaplan-Meier method and multivariable analysis by Cox regression. Statistical significance was set at p< 0.05. RESULTS No significant differences in OS and PDRS were noted between the two groups when comparing age at diagnosis, menopausal status, tumor histopathology, pathological stage, axillary lymph node involvement, and hormone receptor and HER2 status. However, median OS and PDRS were significantly longer for patients who received IM compared to those who did not. The hazard of death was 59% lower with IM than with NI for both OS (HR 0.59: 95% CI 0.42 – 0.83; p=0.002) and for PDRS (HR 0.59: 95% CI 0.42 – 0.84). On multivariable analysis, OS was improved among patients with IM, and among those with lung metastases, compared to liver and bone metastases. CONCLUSIONS Metastatic site intervention had both an OS and PDRS benefit in this cohort. In order to explore the potential for interventions to their metastases, patients who develop limited metastatic disease following initial breast surgery should be discussed at a multidisciplinary tumor board. Post-Distant Recurrence Survival in Patients with Breast Cancer Receiving Intervention to Metastatic Lesions (IM) Versus No Intervention (NI) Citation Format: Hira Abidi, Serdar Ozbas, Beyza Ozcinar, Lutfi Dogan, Arda Isik, Emilia Diego, Priscilla F. McAuliffe, Ronald Johnson, Jennifer Steiman, Efe Sezgin, Atilla Soran. Intervention to Distant Metastatic Lesions in Patients with Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-42.

Objectives:In differentiated thyroid cancer (DTC), radioiodine (RAI) therapy is most frequently employed for remnant ablation or as adjuvant therapy for the remaining disease. The application of RAI to patients classified as intermediate risk (InR) is still a matter of debate. The aim of this study is to analyze the effect of early postoperative risk assessment on RAI use on papillary thyroid cancer patients who are classified as low risk (LoR) or InR. Methods:This is a single-center, prospective registry study. One-hundred-eighty-six patients operated between January 2012 and August 2021 and categorized as LoR or InR were included in this study. All patients had total thyroidectomy and central lymph node dissection by the same endocrine surgeon. An early dynamic risk assessment (EDRA) consisting of neck ultrasonography, serum thyroglobulin (Tg) and anti-Tg levels was performed 6 weeks after surgery. Most of the patients were either followed up without RAI or received ablative low activity (30-50 mCi) RAI based on predetermined criteria. Results:Median follow-up was 63 months. Sixty-six (61%) patients in the LoR group and 43 (56%) patients in the InR group did not receive RAI treatment. Thirty-eight (35%) and 22 (29%) patients in LoR and InR groups received ablative (30-50 mCi) RAI therapy, respectively. In LoR group 5 (4.6%) patients and in InR group 12 (16%) patients received 100 mCi or more RAI activity. Only one patient in the InR group recurred during follow-up. No statistically significant difference regarding local recurrence was found between patients who didn't receive RAI or were treated with RAI within both LoR (p=0.152) and InR (p=0.272) groups. Conclusion:There is consensus for LoR patients about omitting RAI therapy after surgery. Indications for RAI treatment in InR DTC are still under debate. RAI use based on EDRA seems to be a better option than decisions solely made on histopathological risk factors and decreases adjuvant high-activity RAI use without increasing recurrence risk.