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Centrosome amplification (CA) is a hallmark of cancer that is strongly associated with highly aggressive disease and worse clinical outcome. Clustering extra centrosomes is a major coping mechanism required for faithful mitosis of cancer cells with CA that would otherwise undergo mitotic catastrophe and cell death. However, its underlying molecular mechanisms have not been fully described. Furthermore, little is known about the processes and players triggering aggressiveness of cells with CA beyond mitosis. Here, we identified Transforming Acidic Coiled-Coil Containing Protein 3 (TACC3) to be overexpressed in tumors with CA, and its high expression is associated with dramatically worse clinical outcome. We demonstrated, for the first time, that TACC3 forms distinct functional interactomes regulating different processes in mitosis and interphase to ensure proliferation and survival of cancer cells with CA. Mitotic TACC3 interacts with the Kinesin Family Member C1 (KIFC1) to cluster extra centrosomes for mitotic progression, and inhibition of this interaction leads to mitotic cell death via multipolar spindle formation. Interphase TACC3 interacts with the nucleosome remodeling and deacetylase (NuRD) complex (HDAC2 and MBD2) in nucleus to inhibit the expression of key tumor suppressors (e.g., p21, p16 and APAF1) driving G1/S progression, and its inhibition blocks these interactions and causes p53-independent G1 arrest and apoptosis. Notably, inducing CA by p53 loss/mutation increases the expression of TACC3 and KIFC1 via FOXM1 and renders cancer cells highly sensitive to TACC3 inhibition. Targeting TACC3 by guide RNAs or small molecule inhibitors strongly inhibits growth of organoids and breast cancer cell line- and patient-derived xenografts with CA by induction of multipolar spindles, mitotic and G1 arrest. Altogether, our results show that TACC3 is a multifunctional driver of highly aggressive breast tumors with CA and that targeting TACC3 is a promising approach to tackle this disease.

Background: We aimed to evaluate the effect of sarcopenia on survival in head and neck squamous cell carcinoma patients treated with chemoradiotherapy. Materials & methods: Disease-free survival and overall survival were compared according to cervical computed tomography for radiotherapy in 123 sarcopenic and non-sarcopenic patients with locally advanced head and neck squamous cell carcinoma treated with chemoradiotherapy with weekly cisplatin. Results: In multivariate analyses, pretreatment sarcopenia was associated with lower disease-free survival (hazard ratio: 2.60; 95% CI: 1.38–4.87; p = 0.003) and overall survival (hazard ratio: 2.86; 95% CI: 1.40–5.85; p = 0.004). Sarcopenic patients experienced more frequent radiotherapy-related toxicities and platinum-related side effects than non-sarcopenic patients. Conclusion: Sarcopenia could be a potential biomarker to predict prognosis and treatment toxicity in head and neck squamous cell carcinoma.

We routinely delineate the gross tumor volume (GTV) for the lymph nodes (LN) based on post-induction chemotherapy (IC) MRI in nasopharyngeal carcinoma (NPC). Herein, we investigated the sufficiency of this method, particularly in high-risk LNs.Eighty-one LNs with a high-risk of clinical extranodal extension and/or ≥3-cm diameter in 58 patients were evaluated. A new GTV covering the pre-IC LN volume was delineated for each LN.The median volume reduction was 72.5% for the GTV and 53.1% for the planning target volume. After a median 43 months, the overall LN local control rate was 97.5%. The 2- and 5-year LN recurrence-free survival, overall survival, and disease-free survival rate was 88.3% and 84.4%, 92.5% and 85.1%, and 86.8% and 79.2%, respectively.IC yields a significant reduction in nodal target volumes, and post-IC nodal volume-based radiotherapy provides excellent LC in NPC, even in high-risk LNs.

Arazi ve Arsa Düzenlemeleri (AAD), planlı şehircilik ilkeleri kapsamında uygulaması yerel yönetimlerce zorunlu olan uygulamalar kapsamındadır. Bu uygulamayla birçok parselin, parsel maliklerinden izin alınmaksızın İmar Kanunun 18. Maddesi ve uygulama yönetmeliği ile Planlı Alanlar Yönetmeliği hükümlerine ve uygulama imar planına göre parselasyonu yapılarak yapılaşmaya uygun hale getirilmektedir. Günümüz meri mevzuatı kapsamında parselasyon planına göre müstakil yapı yapılmasına müsait tapuya tescilli imar parseli üretimine ilişkin uygulamalar alan esaslı ve kısmen değer esaslı olarak yapılmakta olup her parselde eşit oranda değer artışı olduğu kabul edilmektedir. Ancak; bu durum her zaman her uygulamada sağlanamamaktadır ve bazı parsellerde diğer parsellere göre daha farklı değer artışları yaşandığı için hukuk dilinde haksız zenginleşmeye yol açmaktadır. İmar uygulamaları çalışmalarında alan esaslı çalışma yerine taşınmazın kadastro ve imar parsel değerlerine göre derece dönüşüm esaslı uygulama stratejisi geliştirilmiş, haksız zenginleşmeyi önleyebilecek daha adil bir model oluşturulmuştur. Çalışmada; Erzurum Büyükşehir Belediyesince kesinleştirilip tapu müdürlüğünce tescil edilen gerçek bir imar uygulaması incelenerek, her parselden eşit Düzenleme Ortaklık Payı (DOP) kesintisi uygulamasına alternatif olacak şekilde, kadastro ve imar parsellerinin değerlerinin oranlanmasından derece dönüşüm modeli geliştirilmiş, imar parseli tahsisinde 1163 sayılı Kooparatifler Kanununun 23. Maddesine uygun olarak şerefiye esaslı tahsis modeli uygulanmış ve imar uygulaması nedeniyle oluşan değer artışı malikler arasında paylaştırılarak değer eşitliği sağlanmıştır.

We aimed to evaluate the seroconversion rates after two doses of inactive COVID-19 vaccine (CoronaVac) and the benefit of a third dose mRNA vaccine booster in patients with cancer receiving active treatment. Patients with solid tumors receiving active treatment (n = 101) and patients with no-cancer (n = 48) as the control group were included in the study. All the patients and controls had received two doses of CoronaVac and a third booster dose of the mRNA vaccine (Bnt162b2). Anti-SARS-CoV-2 Spike Receptor Binding Domain IgG antibody levels after the second and third dose were measured with quantitative ELISA. The median age of the patients was 66 (IQR 60-71). 79% of the patients were receiving chemotherapy, and 21% were receiving immunotherapy at the time of vaccination. Antibody levels measured after two doses of CoronaVac were significantly lower in patients with cancer than in the control group (median 0 μg/ml [IQR 0-1.17 μg/ml] vs median 0.91 μg/ml [IQR 0-2.24 μg/ml], respectively, P = .002). Seropositivity rates were 46.5% in patients with cancer and 72.9% in the control group (P = .002). Antibody measurement was performed in 26 patients after the third dose. Seroconversion rate increased from 46.5% to 88.5% (P .001), and the antibody titers significantly increased with the third-dose booster (median 0 μg/ml [IQR 0-1.17 μg/ml] after two doses vs 12.6 μg/ml [IQR 1.8-69.1 μg/ml] after third booster dose, P .001). Immunogenicity of CoronaVac is low in patients with cancer receiving active treatment, and administering a third dose of an mRNA vaccine is effective in terms of improving seroconversion rates.

Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference.

The HER2-low breast cancer is a newly recognized entity with the clinical characteristics is yet to be defined. We hypothesized that HER2-low breast cancer could lead to an increased rate of brain metastases in patients with localized breast cancer. We tested this hypothesis in a large cohort of breast cancer patients with long follow-up. We included 2686 adult breast cancer patients followed up in Hacettepe University Cancer Center. Patients with 1 + positive HER2 expression and 2 + HER2 expression with a negative FISH were categorized as HER2-low disease. We evaluated the brain metastasis risk with binary logistic regression analyses and reported odds ratios (OR) with 95% confidence intervals (CI). During a median 95.4 (IQR 72.6–123.1) month follow-up, 184 patients developed brain metastasis (6.9%). The brain metastases were developed in 5.1% of the patients with HER2-negative disease, 8.5% of the patients with HER2-low disease, and 10.1% of the patients with HER2-positive disease. A multivariable binary logistic regression model demonstrated an increased risk of brain metastasis in patients with HER2-low disease (OR: 1.611, 95% CI 1.055–2.460, p = 0.027) and in HER2-positive patients (OR: 1.837, 95% CI 1.308–2.580, p

Hypophysitis is rarely reported in patients receiving pembrolizumab-only immunotherapies. Since the clinical presentation is usually as isolated adrenocorticotrophic hormone (ACTH) deficiency, patients may be misjudged as having clinical symptoms due to cancer or chemotherapy. A 49-year-old male with laryngeal cancer applied to our clinic just after the tenth cycle of his pembrolizumab treatment, with weakness and nausea/vomiting. Serum morning cortisol and ACTH were 0.47 mcg/dl and 10.1 pg/ml, respectively; the remaining anterior pituitary hormone levels were normal. Pituitary MRI revealed mild glandular enlargement and loss of posterior pituitary bright-spot. All symptoms and signs improved with low-dose prednisolone. This is the second reported case of pembolizumab-associated isolated ACTH deficiency having abnormal pituitary MRI findings as we have reviewed all reported cases in the literature.Lay abstract Immune check point inhibitors (ICIs) are used in order to enhance antitumoral immune mechanisms in certain cancers. As a result, immune-related side effects have commonly been reported in patients taking ICIs, one of which is hypophysitis. Pembrolizumab is a type of ICI which has rarely been associated with hypophysitis. Since the clinical presentation of pembrolizumab-associated hypophysitis is usually as isolated adrenocorticotrophic hormone deficiency and related cortisol insufficiency, patients may be misjudged as having clinical symptoms due to cancer or chemotherapy, due to shared symptoms such as fatigue, loss of appetite and nausea. Here we have reported a case with pembrolizumab-associated isolated adrenocorticotrophic hormone deficiency and reviewed all other cases available in the literature to improve our understanding of such patients.

Aim: Blood-based biomarkers like prognostic nutritional index (PNI) are readily available biomarkers for immunotherapy efficacy, although the data are limited. So, we aimed to evaluate the association between PNI and overall survival (OS) in immunotherapy-treated patients. Materials & methods: For this retrospective cohort study, data of 150 immunotherapy-treated advanced cancer patients were evaluated. The association between clinical factors and OS was evaluated with multivariate Cox-regression analyses. Results: After a median follow-up of 8.5 months, 94 patients died. The median OS was 11.07 months. The low PNI (hazard ratio [HR]: 2.065; p = 0.001), high lactate dehydrogenase (HR: 2.515; p = 0.001) and poor Eastern Cooperative Oncology Group (ECOG) status (HR: 2.164; p = 0.009) was associated with poorer OS in multivariate analyses. Conclusion: In our experience, survival with immunotherapy was impaired in patients with lower PNI and higher lactate dehydrogenase levels and poorer ECOG status. WOS:000685162800001 34397271 Q3

A significant portion of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) relapse despite multimodality treatment denoting the need for biomarkers. The pan-immune-inflammation value (PIV) is a recently developed blood count-based prognostic biomarker. We evaluated the relationship between PIV and survival in locally advanced HNSCC patients treated with chemoradiotherapy (CRT).A total of 199 patients who underwent CRT at Hacettepe University Oncology Hospital were included. The relationship between clinical and laboratory parameters with overall survival (OS) and disease-free survival (DFS) was analyzed by multivariate analyses.The median age was 59 years and 90.5% of the patients were male. 66.8% of the patients had laryngeal primaries, and 78.9% had T3-T4 disease. 84.9% of the patients received CRT with cisplatin. The optimal PIV threshold value was calculated as 404 in ROC analyses. This PIV value had 75.8% sensitivity and 70.4% specificity for OS prediction (AUC 0.781; 95% CI 0.715-0.846; p 0.001). In multivariate analyses, high PIV levels (≤ 404 vs. 404, HR 2.862; 95% CI 1.553-5.276; p = 0.001), higher NLR (≤ 2.5 vs. 2.5, HR 1.827; 95% CI 1.017-3.281; p = 0.044) levels and ECOG performance score of 2 (HR 2.267; 95% CI 1.385-3.711; p = 0.001) were associated with shorter OS. These factors were associated with shorter DFS also (HR for PIV 2.485, 95% CI 1.383-4.467, p = 0.002).We observed shorter OS and DFS in locally advanced HNSCC patients with high PIV levels. If prospective studies support our findings, the PIV score could be a prognostic biomarker in HNSCC.

Purpose: With the widespread use of immunotherapy agents, we encounter treatment responses such as hyperprogression disease (HPD) that we have not seen with previous standard chemotherapy and targeted therapies. It is known that survival in patients with HPD is shorter than in patients without HPD. Therefore, it is important to know the factors that will predict HPD. We aimed to identify HPD-related factors in patients treated with immunotherapy. Methods: A total of 121 adult metastatic cancer patients treated with immunotherapy for any cancer were included. Baseline demographics, the ECOG performance status, type of tumors and baseline blood count parameters were recorded. Possible predisposing factors were evaluated with univariate and multivariate analyses. Results: The median age was 62.28 (interquartile range (IQR) 54.02–67.63) years, and the median follow-up was 12.26 (IQR 5.6–24.36) months. Renal cell carcinoma (33%) and melanoma (33.8%) were the most common diagnoses. Twenty patients (16.5%) had HPD. A high LDH level (p: 0.001), hypoalbuminemia (p: 0.016) and an NLR > 5 (p: 0.007) were found to be associated with hyperprogression. Sex (female vs. male, p: 0.114), age (>65 vs. 5 (p: 0.007).

OBJECTIVES: To evaluate the ocular surface, meibomian glands and corneal structural changes using in vivo confocal microscopy (IVCM) in patients receiving aromatase inhibitor (AI) therapy due to the breast cancer. METHODS: This prospective observational study included 13 patients undergoing AI therapy. The patients were evaluated before the treatment, at 3- and 6-month timepoints of AI therapy. To examine the ocular surface and tear film, corneal sensitivity (CS) measurement with Cochet–Bonnet Aesthesiometer, tear film break-up time (TBUT), lissamine green (LG) staining, Schirmer I test with anaesthesia (ST) and the ocular-surface disease index (OSDI) questionnaire were performed consecutively. Corneal cell densities and sub-basal nerve plexus were evaluated with IVCM (ConfoScan 4, Nidek, Japan). Finally, quantitative MG drop-out assessment was made using infrared meibography. Shapiro Wilk, Friedman’s and Post-hoc Dunn tests were used for the statistical analysis. RESULTS: TBUT, ST scores, basal epithelium, anterior and posterior keratocytes and endothelial cell densities, long and total sub-basal nerve densities were found to be decreased (p

Objective: Treatment beyond progression (TBP) with immune checkpoint inhibitors (ICIs) is an evolving field due to the limitations of conventional imaging in response evaluation with ICIs. However, real-life data on the benefit of TBP is scarce, especially from the limited resource settings. Therefore, we aimed to investigate the survival benefit of TBP with ICIs in patients with advanced tumors from a limited resource setting.Methods: For this multicenter study, we included 282 patients treated with ICIs and radiological progression according to RECIST 1.1 criteria. The evaluated post-progression survival according to the use of TBP (TBP and non-TBP groups) with univariate and multivariate analyses.Results: 82 (29.1%) of 282 patients continued on ICIs following the initial progression event. In multivariate analyses, patients in the TBP group had improved post-progression survival compared to non-TBP (13.18 vs. 4.63 months, HR: 0.500, 95% CI: 0.349-0.717, pConclusions: In this study, we observed that patients receiving ICIs beyond progression had considerably longer survival. Continuation of ICIs after progression should be kept in mind as a reasonable management option for patients with advanced cancer, specifically for patients with limited alternative options.

Dynamic changes in the blood-based biomarkers could be used as a prognostic biomarker in patients treated with immune checkpoint inhibitors (ICIs), although the data are limited. We evaluated the association between the neutrophil–lymphocyte ratio (NLR) and early NLR changes with survival in ICI-treated patients. We retrospectively evaluated the data of 231 patients with advanced-stage cancer. We recorded baseline clinical characteristics, baseline NLR and fourth-week NLR changes, and survival data. A compound prognostic score, the NLR2-CEL score, was developed with the following parameters: baseline NLR (

Purpose/objective(s) Metastasis- directed therapy (MDT) utilizing stereotactic body radiotherapy (SBRT) for oligoprogressive lesions could provide a delay in next-line systemic treatment (NEST) change while undergoing androgen receptor-targeted agents (ARTA) treatment. We evaluated prognostic factors for prostate cancer-specific survival (PCSS) and progression-free survival (PFS) to characterize patients receiving treatment with ARTA who may benefit from MDT for oligoprogressive lesions. The impact of MDT on delaying NEST and the predictive factors for NEST-free survival (NEST-FS) were also assessed. Materials/methods The clinical data of 54 metastatic castration-resistant prostate cancer patients with 126 oligoprogressive lesions receiving abiraterone (1 g/day) or enzalutamide (160 mg/day) before or after systemic chemotherapy were analyzed. A median of three lesions (range: 1-5) were treated with MDT. The primary end points were PCSS and PFS. The secondary end points were time to switch to NEST and NEST-FS. Results The median follow-up time was 19.1 months. Univariate analysis showed that the number of oligoprogressive lesions treated with SBRT and the time between the start of ARTA treatment and oligoprogression were significant prognostic factors for PCSS, and the timing of ARTA treatment (before or after chemotherapy) and the PSA response after MDT were significant prognostic factors for PFS. Multivariate analysis showed that early MDT for oligoprogressive lesions delivered less than six months after beginning of ARTA [HR = 3.20 (95% CI, 1.12-9.15); P = 0.03] and higher PSA levels after MDT [HR = 1.01 (95% CI 1.00-1.01), P = 0.02] were significant predictors of worse PCSS and PFS. The median total duration of ARTA treatment was 13.8 months. The median time between the start of ARTA treatment and the start of MDT for oligoprogressive lesions was 5.2 months, and MDT extended the ARTA treatment by 8.6 months on average. Thirty-two (59.3%) patients continued ARTA treatment after MDT. ARTA treatment after chemotherapy, early oligoprogression requiring MDT, and lower radiation doses for MDT were independent predictors of NEST-FS in multivariate analysis. Conclusion MDT for oligoprogressive lesions is effective and may provide several benefits compared to switching from ARTA treatment to NEST. Patients with early progression while on ARTAs and inadequate PSA responses after MDT have a greater risk of rapid disease progression and poor survival, which necessitates intensified treatment.

Purpose The aims of this study were to investigate if/how the presence of lymphedema affects the sensation of the upper limb and to assess whether complex decongestive physiotherapy (CDP) has a favorable impact on sensory testing. Methods A total of 27 patients with unilateral stage 2 breast cancer–related lymphedema (BCRL) were included in the study. Bilateral circumferential measurements were taken with a tape measure at different levels. Based on these measurements, limb volumes were determined by summing segment volumes derived from the truncated cone formula. Circumferential measurements and ultrasonographic evaluations (epidermis, dermis, and subcutaneous fat thicknesses) were performed at 10 cm distal to the elbow crease. The Semmes–Weinstein monofilament (SWM), static and moving two-point discrimination, pressure pain threshold (PPT), and tactile localization tests were also applied at the same site. After an initial evaluation, all patients underwent CDP phase 1 program. All the evaluations were repeated at the end of the treatment period. Results Before CDP, affected sides had significantly higher values than the unaffected sides in terms of SWM (p

Objective Immunocompromised patients are at a greater risk of developing intestinal parasite infections. In this study, we examined the presence of Enterocytozoon bieneusi, Encaphalitozoon intestinalis and other intestinal protozoa in stool samples of immunosuppressed patients. Methods A total of 100 stool samples were obtained from patients receiving chemotherapy because of solid organ tumour with haematological malignancies and those receiving immunosuppressive treatment because of rheumatic diseases, organ transplant patients and patients receiving treatment for HIV-related infections. Stool samples were examined by using the native-lugol method in which the stool concentration, modified Kinyoun acid-fast and trichrome staining methods and parasite presence were analysed. The stool samples were also examined for the presence of Enterocytozoon bieneusi and Encephalitozoon intestinalis using an indirect fluorescent antibody method. Results Intestinal parasites were detected in 12% of all patients. The distribution of intestinal parasites in patients were 7% Blastocystis spp., 2% Blastocystis spp. + Dientamoeba fragilis, 1% Blastocystis spp. + Entamoeba coli, 1% Blastocystis spp. + Giardia intestinalis and 1% G. intestinalis. Microsporidia spp. were detected in 4% of all patients by the IFAT method and in 8% of all patients by calcoflour staining method. Conclusion In our study, the most prevalent parasite detected in the immunosuppressed patients was Blastocystis spp. The pathogenesis of Blastocystis spp. remains to be controversial, and their role in immunocompromised patients continues to remain unknown. Although these rates detected in our study are similar to the prevalence in the normal population, it is important to study these microorganisms in immunocompromised patients in terms of the associated decreasing morbidity and mortality rates.

This multicenter registry study aims to analyze time-related changes in the treatment patterns and outcome of patients with metastatic breast cancer (MBC) over a ten-year period. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates consisting of cohorts based on disease presentation (recurrent vs. de novo) and the diagnosis date of MBC (Cohort I: patient diagnosed between January 2010 and December 2014; and Cohort II: between January 2015 and December 2019). Out of 1382 patients analyzed, 52.3% patients had recurrent disease, with an increased frequency over time (47.9% in Cohort I vs. 56.1% in Cohort II, p < 0.001). In recurrent patients, 38.4% (n = 277) relapsed within two years from initial diagnosis, among which triple-negative BC (TNBC) was the most frequent (51.7%). Median overall survival (OS) was 51.0 (48.0–55.0) months for all patients, which was similar across both cohorts. HER2+ subtype had the highest OS among subgroups (HER2+ vs. HR+ vs. TNBC; 57 vs. 52 vs. 27 months, p < 0.001), and the dnMBC group showed a better outcome than recMBC (53 vs. 47 months, p = 0.013). Despite the lack of CDK inhibitors, luminal A patients receiving endocrine therapy had a favorable outcome (70 months), constituting an appealing approach with limited resources. The only survival improvement during the timeframe was observed in HER2+ dnMBC patients (3-year OS Cohort I: 62% vs. Cohort II: 84.7%, p = 0.009). The incorporation of targeted agents within standard treatment has improved the outcome in HER2+ MBC patients over time. Nevertheless, despite advances in early diagnosis and treatment, the prognosis of patients with TNBC remains poor, highlighting the need for more effective treatment options.

In DESTINY-Breast01 (NCT03248492) and DESTINY-Breast03 (NCT03529110), trastuzumab deruxtecan (T-DXd) demonstrated unprecedented activity in patients (pts) with HER2+ (immunohistochemistry 3+; immunohistochemistry 2+/in situ hybridization+) advanced metastatic breast cancer (mBC), leading to regulatory approvals in several countries for HER2+ unresectable/mBC after a prior anti–HER2-based regimen. DESTINY-Breast02 (NCT03523585) is a phase 3 trial of T-DXd vs treatment of physician’s choice (TPC) in patients with centrally confirmed HER2+ mBC previously treated with trastuzumab emtansine (T-DM1). It acts as a confirmatory study for the pivotal phase 2 DESTINY-Breast01 trial. Here we report the primary results of DESTINY-Breast02. Methods: Pts with HER2+ mBC were randomized 2:1 to receive T-DXd or TPC (trastuzumab + capecitabine or lapatinib + capecitabine) and stratified by hormone receptor (HR) status (HR+/HR-), prior pertuzumab treatment, and history of visceral disease. The primary endpoint of this time-driven primary analysis was progression-free survival (PFS) as determined by blinded independent central review (BICR). The powered secondary endpoint was overall survival (OS). Other secondary endpoints included confirmed objective response rate (ORR) by BICR, duration of response (DoR) by BICR, PFS by investigator assessment, safety, and others. Results: 608 pts were randomized to receive T-DXd (n = 406) or TPC (n = 202). Pts receiving T-DXd and TPC had a median age of 54.2 years (range, 22.4-88.5 years) and 54.7 years (range, 24.7-86.5 years), respectively, with a median of 2 (range, 0-10 and range,1-8) prior lines of systemic therapy (excluding hormone therapy) in the metastatic setting. Median treatment duration was 11.3 mo in the T-DXd arm and ~4.5 mo in the TPC arm. Efficacy and safety results are shown in the table below. T-DXd significantly improved PFS (HR, 0.36; 95% CI, 0.28-0.45; P Conclusions: Results from DESTINY-Breast02 confirmed the clinical benefit and superiority of T-DXd over conventional chemotherapy-based regimens in pts with HER2+ mBC previously treated with T-DM1, as evidenced by significant and clinically meaningful improvements in PFS and OS. These data, together with earlier reported results from the DESTINY-Breast03 study of T-DXd vs T-DM1 solidify T-DXd as an optimal treatment option in pts with progressive HER2+ mBC across broad settings. Editorial Acknowledgment Under guidance of the authors, assistance in medical writing and editorial support was provided by Caylin Bosch, PhD, of ApotheCom, and was funded by Daiichi Sankyo. Funding This study was funded by Daiichi Sankyo and AstraZeneca. Table. Summary of Efficacy and Safety Results for T-DXd and TPC in Patients With HER2+ mBC Previously Treated With T-DM1 Citation Format: Ian Krop, Yeon H. Park, Sung-Bae Kim, Giuliano Borges, Sercan Aksoy, Joaquin Gavila Gregori, Rebecca Roylance, Elgene Lim, Rinat Yerushalmi, Flora Zagouri, Francois P. Duhoux, Tanja Fehm, Toshimi Takano, Anton Egorov, Iris Wu, Jillian Cathcart, Changan Chu, Fabrice Andre. GS2-01 Trastuzumab deruxtecan vs physician’s choice in patients with HER2+ unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine: primary results of the randomized, phase 3 study DESTINY-Breast02 [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 GS2-01.

Background: Although HER2 is an aggressive subtype of BC, the outcomes have improved over the past two decades due to advances in targeted therapies. Here, we present data of HER2-positive subset from the multicenter registry study of the Turkish Oncology Group (TOG) for metastatic breast cancer with an evolving treatment landscape for over a decade (MBC). Methods: The study of TOG for MBC was a retrospective registry study aimed to collect the data of adult metastatic BC patients diagnosed between 2010-2019, at seven tertiary oncology clinics in Turkey. Patient and disease characteristics were recorded from chart reviews. HER2 (+) was defined as IHC scores of IHC3+ or IHC2+ and ISH (+). Overall survival (OS) and progression-free survival (PFS) were calculated by the Kaplan-Meier method. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates comprising of cohorts based on disease presentation (recurrent vs de-novo) and the diagnosis date of MBC (Cohort I: patient diagnosed between January 2010-December 2014 and Cohort II: between January 2015-December 2019). Results: Of the 1381 patients analyzed over the whole period, 333 (24.1%) HER2 (+) MBC patients were identified. 55.0% of the patients were in Cohort I. The majority (56.8%) had de novo MBC. Despite a decreasing frequency over time (63.4% in Cohort I vs 48.7% in Cohort II, p=0.007), this was the largest group with among all pathological subgroups presenting with de novo disease. 17 patients (2.4% of recurrent patients) demonstrated changes in HER2 receptor status from negative to positive between the primary tumor and subsequent metastasis. Recurrent BC patients were significantly younger than de novo MBC patients [44 (22-80) years vs 49 (20-91) years, p=0.006] and 43.1% (n=62) had relapsed within two years from initial diagnosis. Recurrent BC patients showed a higher frequency of brain metastasis as compared to de novo patients (13.2% vs 1.1%), whereas non-CNS visceral organ metastases were more common in de novo MBC patients (58.7% vs 47.9%, respectively, p< 0.001). Following conditional approval of use in de novo visceral metastatic disease in 2016, dual-HER2 blockade including pertuzumab was more frequently used in Cohort II compared to Cohort I (p< 0.001). Although overall median PFS was not statistically significant between the two cohorts (Cohort II vs I; 22 vs 17 months, respectively, p=0.609), there was a significantly higher PFS in the de novo group in Cohort II (29 vs 17 months, p=0.037). Furthermore, there was a significant improvement in median OS in Cohort II compared to Cohort I [not reached vs 48.0 (40.0-71.0) months, respectively; p=0.017]; mainly driven by the de novo group in alignment with the approval indication for dual blockade (Cohort I vs II; 3-year OS; 62.0% vs 84.7%; p=0.009); especially those with visceral metastatic presentation (59.4% vs 83.4%, p=0.020); HR (+) HER2 (+) disease (61.2% vs 89.2%; p=0.013) and age< 40 years (40.0% vs 94.7%; p=0.009). Conclusion: There was a significant survival benefit achieved in patients with metastatic HER2 (+) disease over time, regardless of high-risk factors such as visceral involvement or young age, mirroring advances in the timeline of anti-HER2 treatment. Citation Format: Yeşim ERALP, İzzet DOĞAN, Sercan Aksoy, Burcu ÇAKAR, Gül BAŞARAN, Özlem ERCELEP, Nil MOLİNAS MANDEL, Taner KORKMAZ, Erhan GÖKMEN, Adnan AYDINER, Pınar SAİP. Demographic and clinical features of patients with metastatic HER2 positive breast cancer: a retrospective multicenter registry study of the Turkish Oncology Group [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 P3-02-06.

BackgroundInvasive breast cancers are characterized by overexpression or amplification of the human epidermal growth factor receptor 2 (HER2) approximately 15 to 25%. Survival outcomes was improved after introduction of Trastuzumab treatment. Trastuzumab treatment was applied mostly with combination chemotherapy regimens at pivotal trials. There were some efforts to avoid the toxicity of combination chemotherapies and reduce the amount of treatment given especially in stage I HER 2 overexpressed breast cancer patients. Adjuvant paclitaxel plus trastuzumab was shown excellent disease free survival (DFS) and overall survival (OS) in node negative, 3 cm and smaller HER 2 overexpressed breast cancer patients. MethodsAll breast cancer patients that treated in Medical Oncology departments of Hacettepe University (Ankara, Turkey), Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital (Ankara, Turkey), Nicosia Dr. Burhan Nalbantoglu State Hospital (Nicosia, Cyprus) and Near East University (Nicosia, Cyprus) were retrospectively reviewed from patient files, center’s databases and chemotherapy files.ResultsWe retrospectively analyzed 173 patients who treated with adjuvant paclitaxel plus trastuzmab between April 1, 2012 and April 10, 2020. Median age was 52 years (range, 25 to 84 years) and 62.4% had estrogen receptor positive disease. 68.8% of the tumors were high-grade. 14.4% of patients had tumors 1 cm or smaller. 45.0% of patients had tumors larger than 2 cm and 32.3% of patients had tumors larger than 2 cm and up to 3 cm. 12.6% of patients had tumors larger than 3 cm. Mean tumor size was 2.2 cm. 88.4% of patients had N0 disease and 2.9% of patients had microscopic nodal metastasis. 164 of 173 patients completed all 52 weeks of adjuvant treatment. Median follow up of 43 months there were 8 DFS events observed: four distant recurrences (2.3%), three locoregional recurrences (1.7%) and one died without documented recurrence. 3-year DFS rate was 96.6%. There was no recurrences in patients who had tumors 1 cm or smaller. There were 5 DFS events in patients had tumors larger than 2 cm and up to 3 cm subgrup. ConclusionThis real life experience with paclitaxel plus trastuzumab demonstrated few distant recurrences and further supports the APT trial findings. Table 2. Events Observed for the Disease-free Survival.EventsPatients (N=173)Time to Eventno. (%)moAny recurrence or death8 (4.6)Local or regional recurrenceIpsilateral axilla, HER2-positive2 (1.1)25, 64Ipsilateral breast, HER2-positive1 (0.6)48Distant recurrence4 (2.3)7, 35, 36, 42DeathNot breast-cancer–related1 (0.6)52 Citation Format: Omer Diker, Burak Yasin Aktas, Recep Ak, Bahadir Koylu, Onur Bas, Polat Olgun, Hakan Taban, Deniz Can Guven, Neyran Kertmen, Berna Oksuzoglu, Sercan Aksoy. Adjuvant treatment with paclitaxel plus trastuzumab for node negative human epidermal growth factor receptor 2-positive breast cancer: Real life experience [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 PS10-52.