The aim of this study is to re-evaluate the decision of adjuvant chemotherapy according to TAILORx trial in our patients included in the prospective clinical study based on NSABP-20 criteria, and to recalculate the cost-effectiveness of ODX RS. Patients were analyzed for cost-effectiveness in the chemotherapy + endocrine therapy or endocrine therapy. The cost-effectiveness analyses of treatment before and after the ODX RS® result were compared according to Tailor X. The deterioration in quality of life during chemotherapy was calculated based on the time the patient was away from daily activities, 6 months of work loss in 1 year and the cost of chemotherapy. ICER (ICER: Incremental Cost-Effectiveness Ratio) was calculated for cost-effectiveness. During a median follow-up period of 108.4 months (range 15.8–111), in 11 (6.7

BACKGROUND:Seventy percent of early-stage breast cancers are hormone receptor positive. In this prospectively designed study, we aim to update the long-term survival outcomes of chemotherapy decision-making according to Oncotype DX Recurrence Score (ODX-RS) and its relation with different cut-offs. MATERIALS AND METHODS:Ten academic centers in Türkiye that routinely discuss all new cases at multidisciplinary tumor board participated. Consecutive patients who are pT1-3, pN0-N1mic, M0 were identified. Adjuvant treatment decisions were discussed at tumor board before and after ODX-RS results. RESULTS:Of the 165 patients (26-76, median 48 years) with a median follow-up of 108 months, ODX-RS ≤ 25 had significantly better overall survival (OS) than those with ODX-RS ≥ 26 (p = 0.022). When evaluated by age, OS and disease-free survival (DFS) was significantly better with ODX-RS ≤ 15 in patients aged ≤ 50 years and with ODX-RS ≤ 25 in patients aged > 50 years (p = 0.034 and p = 0.024). ODX-RS ≤ 20 in patients aged ≤ 50 years and ODX-RS ≤ 25 in patients aged > 50 years had significantly better OS (p = 0.002). There was no difference in OS between those who received chemotherapy before ODX-RS and those who did not (p = 0.119). Conversely in the post-ODX-RS, ODX-RS predicted survival better and OS was lower in patients who received chemotherapy compared to those who did not (p = 0.020) meaning that ODX-RS can predict OS. The ODX-RS test significantly reduced overall chemotherapy-related costs, yielding a favorable ICER of $3787.5 per QALY gained, thus demonstrating its cost-effectiveness. CONCLUSIONS:The ODX-RS significantly influences treatment decisions resulting comparable survivals for patients who received chemotherapy and who did not. Different cut-offs have variable significant prognostic effect on survival prediction models.

545 Background: In non-developed and developing countries, the 21 gene assay (Oncotype DX) test is expensive and not covered by private and social health insurance, which limits its use. However, clinicians need this test for treatment prediction in early stage breast cancer. Therefore, we aimed to predict the risk of recurrence in patients using artificial intelligence (AI) algorithms. Methods: This study was conducted with 437 early-stage breast cancer patients whose recurrence risk scores were determined by 21 Oncotype DX and were followed in 14 oncology centers in Turkey between 2012 and 2022. The optimum cut-off for the 21 gene assay risk score (RS) was found by ROC analysis using the patients' recurrence information (scale of RS ≥17: high risk, <17: low risk). In artificial intelligence prediction models, patients with a 21 gene assay risk score ≥17 were considered high risk. Additionally, algorithm predictions were made within other cut-offs recommended in the literature (<10, 11-25, >25). Python programming language was used in the analyses. The Random Forest (RF), Logistic regression (LG) and K-Nearest Neighbors (KNN) were used as AI prediction algorithms. Results: The study analyzed 437 women with an average age of 49.49±10.30. During the follow-up period from 2012 to 2022, 7.1% of the patients experienced a recurrence. AI prediction algorithms which were RF, LG, and KNN generated confusion matrices for two classes, with a threshold of 17 and 25. The algorithms were then applied to the dataset with risk score thresholds of 1-10, 11-25, and greater than 25, resulting in three classes. The dataset was analyzed using recall, precision, and F1 score values. The results showed that RF had the most accurate predictions for RS = 17 (Table). Conclusions: The use of artificial intelligence algorithms in predicting the risk of recurrence in early stage breast cancer is promising in determining treatment decisions for clinicians who cannot access genetic results. [Table: see text]

BackgroundThe Oncotype Dx recurrence score (ODx-RS) guides the adjuvant chemotherapy decision-making process for patients with early-stage hormone receptor-positive, HER-2 receptor-negative breast cancer. This study aimed to evaluate survival and its correlation with ODx-RS in pT1-2, N0-N1mic patients treated with adjuvant therapy based on tumor board decisions.Patients and methodsEstrogen-positive HER-2 negative early-stage breast cancer patients (pT1-2 N0, N1mic) with known ODx-RS, operated on between 2010 and 2014, were included in this study. The primary aim was to evaluate 5-year disease-free survival (DFS) rates according to ODX-RS.ResultsA total of 203 eligible patients were included in the study, with a median age of 48 (range 26-75) and median follow-up of 84 (range 23-138) months. ROC curve analysis for all patients revealed a recurrence cut-off age of 45 years, prompting evaluation by grouping patients as ≤45 years vs. >45 years. No significant difference in five-year DFS rates was observed between the endocrine-only (ET) and chemo-endocrine (CE) groups. However, among the ET group, DFS was higher in patients over 45 years compared to those aged ≤45 years. When stratifying by ODx-RS as 0-17 and ≥18, DFS was significantly higher in the former group within the ET group. However, such differences were not seen in the CE group. In the ET group, an ODx-RS ≥18 and menopausal status were identified as independent factors affecting survival, with only an ODx-RS ≥18 impacting DFS in patients aged ≤45 years. The ROC curve analysis for this subgroup found the ODx-RS cut-off to be 18.ConclusionThis first multicenter Oncotype Dx survival analysis in Turkey demonstrates the importance of Oncotype Dx recurrence score and age in determining treatment strategies for early-stage breast cancer patients. As a different aproach to the literature, our findings suggest that the addition of chemotherapy to endocrine therapy in young patients (≤45 years) with Oncotype Dx recurrence scores of ≥18 improves DFS.

Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood. Aims: To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed. Study Design: Multicenter retrospective observational cohort study. Methods: In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2- metastatic breast cancer. Results: The median progression-free survival in our population was 7 months (25th-75th percentile, 4-10), and the median overall survival was 11 months (25th-75th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%). Conclusion: The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2- patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.

Objective: Breast cancer is a heterogenous disease, and genetic profiling helps to individualize adjuvant treatment. The Oncotype DX is a validated test to predict benefit of adjuvant systemic treatment. The aims of this study are to determine the costs of chemotherapy in government hospitals in Turkey and evaluate the cost-effectiveness of the Oncotype DX from the national insurance perspective. Materials and Methods: A Markov model was developed to make long term projections of distant recurrence, survival, quality adjusted life expectancy, and direct costs for patients with ER+, HER2-, node-negative or up to 3 node-positive early stage breast cancer. Turkish decision impact study patient data were captured for model reference. In that study, ten academic centers across Turkey participated in a prospective trial. Of 165 patients with pT1-3, pN0-N1mic, ER-positive, and HER-2 negative tumors, 57% had low recurrence score (RS), 35% had intermediate RS, and 8% had high RS, respectively. The overall rate of change in chemotherapy treatment decisions following Oncotype DX was 33%. Results: The cost of adjuvant chemotherapy in public hospitals was estimated at $3.649, and Oncotype Dx test was $5.141. Based on the cost-effectiveness analysis, Oncotype DX testing was estimated to improve life expectancy (+0.86 years) and quality-adjusted life expectancy (+0.68 QALYs) versus standard care. The incremental cost-effectiveness ratio (ICERs) of Oncotype DX was estimated to be $7207.9 per QALY gained and $5720.6 per LY gained versus current clinical practice. Conclusion: As Oncotype DX was found both cost-effective and life-saving from a national perspective, the test should be introduced to standard care in patients with ER+, HER-2 negative early-stage breast cancer in Turkey.

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.

Introduction: 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 impact of the Recurrence Score® (RS) on treatment decisions and physician perceptions in Turkey. We also studied correlations between RS and routine risk factors. Patients and Methods: Ten academic centers across Turkey participated in this prospective trial. Consecutive breast cancer patients with pT1-3, pN0-N1mic, ER-positive, and HER2-negative tumors were identified at multidisciplinary tumor conferences. The initial treatment decision was recorded before tumor blocks were sent to the central laboratory. Each case was brought back to tumor conference after receiving the RS result. Both pre- and post-RS treatment decisions and physician perceptions were recorded on questionnaire forms. Correlations between RS and classical 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 165 patients, 57% had low RS, 35% had intermediate RS, and 8% had high RS, respectively. The overall rate of change in treatment decision was 33%. Initially, chemotherapy followed by hormonal therapy (CT+HT) was recommended to 92 (56%) of all patients, which decreased to 61 (37%) patients post-RS assay (p<0.001). Multivariate analysis indicated that progesterone receptor (PR) and Ki-67 scores were significantly related to RS. Conclusion: Oncotype DX testing may provide meaningful additional information in carefully selected patients.

Optimal duration of adjuvant trastuzumab in early breast cancer is an unresolved issue. In this observational study, we compared the outcome of 9 weeks and 1 year adjuvant trastuzumab in early breast cancer patients in Turkey.

e11515 Background: The 21-gene Oncotype DX assay is accepted as an important predictive factor in the adjuvant treatment of node negative, estrogen receptor (ER) positive and HER2 (-) breast cancer. The test is not widely available for Turkish physicians as itÕs currently not reimbursed.We performed a prospective analysis to find the impact of the Recurrence Score result (RS) on treatment decisions. Methods: Ten centers across Turkey participated in this prospective trial. Consecutive breast cancer patients with pT1-3, pN0-N1mic, ER(+) , and HER2 (-) tumors were identified and adjuvant treatment decisions were made at breast tumor boards. The pre assay treatment decision was recorded on a questionnaire form. Cases were discussed at tumor boards again when the RS was available and investigators filled the post-assay questionnaire forms with the final decision. Results: 165 patients were enrolled. Mean age was 49.8 (SD±10.3) years. 108(65.5%) patients had pT1 tumors. Mean RS was 18.8±14.0. RS was low in 56.8%, intermediate in in 35.2% and high in 8.5%. There was an overall treatment decision change in 33% of patients with a reduction of chemotherapy (CT) from 56% to 35% overall and a 48% reduction in patients originally recommended CT. Among the patients with low and intermediate results, the decision changed from CT to Òhormonal therapy (HT) aloneÓ in 36 (85.7%) and 7 (36.8%) patients, respectively. Conclusions: The 21-gene assay has a significant impact on treatment decisions at specialty tumor boards in Turkish hospitals. Our initial findings warrant further consideration for the use of this genomic assay in patients with early stage breast cancer in Turkey. Health economic analysis will be reported separately in the near future. Chemotherapy decision in patients before and after RS by risk groups. Post-RS Decision HT CT+HT N n % n % p value* Pre-RS Decision All patients HT 73 63 86.3 10 13.7 <0.001 CT+HT 92 44 47.8 48 52.2 Total 165 107 64.8 58 35.2 Low RS HT 51 51 100.0 0 0.0 CT+HT 42 36 85.7 6 14.3 Total 93 87 93.5 6 6.5 Intermediate RS HT 19 12 63.2 7 36.8 CT+HT 39 8 20.5 31 79.5 Total 58 20 34.5 38 65.5 High RS HT 3 0 0.0 3 100.0 CT+HT 11 0 0.0 11 100.0 Total 14 0 0.0 14 100.0 *McNemar test

Case Discussion A 70-year-old female patient presents to the breast clinic for annual screening. She has no family history of breast cancer. Her physical examination is normal, however an area of 0.5cm in size located in the lower inner quadrant of the right breast has microcalcifications and the adjacent area of approximately 2cm shows structural distortion on mammography (BIRADS 5). The core biopsy reveales high grade, solid ductal carcinoma in situ that contains areas of comedo necrosis and invasive ductal carcinoma in one border. The estrogen receptor (ER) (+), progesterone receptor (PR) (-), Her 2 (-) and Ki-67 is reported as 12% . The patient undergoes segmental mastectomy with wire guide and sentinel lymph node biopsy (SLNB). A 1% isosulfane blue and gamma probe is used for the detection of SLN. One SLN that was not macroscopically suspicious is sent to the pathology department peroperatively, without a request for frozen section evaluation. The paraffin section examination shows a grade 3, ER (+), PR (-) and HER- neu2n (-) invazive tumor with a 2 cm integrity diameter. Lymphovascular invasion (LVI) is positive, and comedo necrosis that surrounds the invasive tumor and forms 15% of the tumor volume are determined, as well as a nuclear grade 3 ductal carcinoma in situ containing microcalcifica tions. The nearest margins to DCIS are 0.3cm at the medial and 0.2cm at the lateral borders, with negative surgical margins. The pathologic evaluation of the aferomentioned single lymph node shows an 8mm metastasis with 0.2 X 0.2 cm extracapsular extension by hematoxylin and eosin (H&E). Is Completion Axillary Dissection Necessary For This Patient?

Objectives: In this study, we tried to evaluate the efficacy of locoregional treatment (LRT) in patients with metastatic breast carcinoma (MBC).Materials and methods: The medical records of 227 patients with MBC at initial presentation between April 1999 and January 2013 were retrospectively evaluated. The median age at diagnosis was 50 years (range, 27-83 years). Thirty-nine patients (17%) had no LRT. Among patients who had LRT, 2 (1%) had locoregional radiotherapy (RT) alone, 54 (29%) had surgery alone [mastectomy, n = 50; breast conserving surgery (BCS), n = 4] and 132 (70%) had surgery (mastectomy, n = 119; BCS, n = 13) followed by locoregional RT.Results: The median follow-up time was 35 months (range, 4-149 months). Five-year OS and PFS rates were 44% and 20%, respectively. In both univariate and multivariate analysis LRT per se did not affect OS and PFS rates. However, the 5-year OS and PFS rates were significantly higher in patients treated with locoregional RT than the ones who were not. The corresponding rates were 56% vs. 24% for OS and 27% vs. 7% for PFS (p < 0.001). Median survival was 67 months and 37 months, respectively.Conclusion: Our study showed that patients with MBC who received postoperative locoregional RT may have a survival advantage compared with patients who were only treated by surgery. A phase III trial testing the role of adjuvant locoregional RT may help to distinguish patients who will benefit from adjuvant RT. (C) 2014 Elsevier Ltd. All rights reserved.

e11553 Background: Systemic chemotherapy is often ineffective due to the impermeability of the blood-brain barrier (BBB) and inherent chemoresistance of CNS metastases. There are limited data supporting the use of capecitabine in this setting. The aim of this study was to evaluate the effectiveness and toxicity of capecitabine in breast cancer patients with CNS metastasis. Methods: The records of all patients with HER-2 Negative breast cancer with CNS metastasis that treated with capecitabine monotherapy were evaluated. All patients recieved capecitabine at a dose of 2,500mg/m2/day for 14 days at 3 weeks intervals. Results: Fifty-eight female patients with a median age of 42 years (min-max; 20-68) were included in this retrospective analysis. The median time to brain metastasis was 3.1 years (min-max; 0.5-15.5). Thirty (51%) patients were hormone positive, and twenty-nine (49%) were triple-negative. Forty-seven (78%) patients recieved capecitabine as first line treatment after the CNS metastasis. Only 4 patients had undergone surgery for CNS metastasis, and all patients had recieved whole brain radiotherapy before the capecitabine treatment. Five (8.5%) patents were treated with cyberknife radiosurgery. There were 6 (10%) complete (2 patient had metastasectomy for brain metastasis), and 21 (36%) partial responses with 9 (15%) patients having stable disease. Progressive disease was observed in 16 (28%) patients. 6 patients were not evaluabled for radiological evaluation. Median progression free survival time was 5 months, and median overall survival was 8.6 months. Dose reduction was required due to adverse effects in 20 patients (24%). The most frequent side effect was the hand-food syndrome (HFS), which developed in 29 patients (50%). Forty-percent of them developed grade 3 HFS disease. Diarrhea occurred in 21% of the patients, nausea in 19% of the patients. Grade 3-4 myelosupression were developed in 15% of the patients. There was no treatment-related death. Conclusions: Capecitabine is effective and well tolerated in the treatment of breast cancer patients with CNS metastases. It is feasible options HER2 negative breast cancer patients especially with neurological deficits.

The aim of this prospective clinical study is to evaluate the relationship between changes in functional cardiac parameters following anthracycline therapy and carbonyl reductase 3 (CBR3p.V244M) and glutathione S transferase Pi (GSTP1p.I105V) polymorphisms. Seventy patients with normal cardiac function and no history of cardiac disease scheduled to undergo anthracycline chemotherapy were included in the study. The patients' cardiac function was evaluated by gated blood pool scintigraphy and echocardiography before and after chemotherapy, as well as 1 year following therapy. Gene polymorphisms were genotyped in 70 patients using TaqMan probes, validated by DNA sequencing. A deteriorating trend was observed in both systolic and diastolic parameters from GG to AA in CBR3p.V244M polymorphism. Patients with G-allele carriers of GSTP1p.I105V polymorphism were common (60%), with significantly decreased PFR compared to patiens with AA genotype. Variants of CBR3 and GSTP1 enzymes may be associated with changes in short-term functional cardiac parameters.

AIMS AND BACKGROUND:Capecitabine, as all fluoropyrimidines, interferes with vitamin metabolism and may thus have an impact on hematopoiesis. It is metabolized to its active form 5-fluoruracil by the enzyme thymidine phosphorylase, which exists in higher concentrations in tumor tissue and liver than in normal tissues. In the study, we investigated the changes in mean corpuscular volume (MCV) of red blood cells and the possible correlation of these changes with the clinical outcome of capecitabine treatment in women with metastatic breast cancer.METHODS AND STUDY DESIGN:Data from 75 metastatic breast cancer patients were analyzed retrospectively. Capecitabine was used at a dose of 2500 mg/m² daily for 14 days of every 3-week period. Mean corpuscular volume of red blood cells and other parameters of complete blood count were recorded at the beginning of the treatment, in the ninth week, and periodically thereafter.RESULTS:Mean age was 51.5 ± 10.8 and 61.3% of the patients were premenopausal. Capecitabine was administered as the median 3rd line (min-max: 1-9) treatment and a median of 6 cycles (min-max: 1-24) for metastatic breast cancer. Median ΔMCV level (post-treatment values at ninth week - baseline) was 8. ΔMCV was ≥8 in 37 patients and <8 in 38 patients. The 35 of the 37 patients with ΔMCV level ≥8 and 25 of the 38 patients with ΔMCV level <8 had clinical benefit (complete response + partial response + stable disease) from capecitabine treatment (P = 0.02). However, the difference between progression-free survival of the patients with ΔMCV levels higher than 8 and those with ΔMCV levels lower than 8 according to Kaplan-Meier survival analysis was not statistically significant (6.7 and 4.3 months, respectively, P = 0.26). Additionally, median ΔMCV level was 9.1 (min-max: -2.4 to 24.9) among patients who had clinical benefit and 5.90 (min-max: -0.8 to 12.3) among nonresponders (P = 0.016).CONCLUSIONS:Capecitabine increases the mean corpuscular volume levels of red blood cells by a yet unidentified mechanism. Early increment of mean corpuscular volume levels is higher than 8, i.e. by the 9th week, might predict clinical benefit from the treatment.