Events In Breast Cancer Patients Research Articles

Abstract PS13-03: Safety of taxane chemotherapy for the treatment of breast cancer during pregnancy: an international cohort study

Abstract Introduction: The addition of taxanes to anthracycline-based chemotherapy regimens offers increased odds of survival in breast cancer (BC) patients. However, some clinicians defer their use in pregnant patients due to limited evidence supporting safety during gestation. The aim of this study is to describe the prevalence of maternal and neonatal adverse events in BC patients exposed to taxane-containing regimens during pregnancy. Methods: This is an international cohort study of BC patients treated with taxane chemotherapy during pregnancy. Inclusion criteria were age ≥18 years, treatment in a participating center (n=10), and completion of pregnancy. Results: A total of 103 women with a median age of 34 years (range 21-44) were included, of whom the majority (91/101; 90.1%) were also exposed to anthracyclines. The median gestational age at initiation of any chemotherapy agent was 16 weeks (range 4-34), while that of taxanes was 28 weeks (range 12-37). Paclitaxel was the most frequently used taxane (100/103; 97.1%), most prescribed as an 80 mg/m2 weekly infusion. All cases were singleton pregnancies except for one twin gestation. The overall live birth rate was 98.0% (100/102). Median gestational age at delivery was 37 weeks (range 32 to 40), with 36/83 live births being preterm (gestational age of < 37 weeks; 43.4%). Median birth weight was 2700 grams (range 1440-4000). The prevalence of grade 3 to 4 adverse events, obstetric complications, and neonatal outcomes are shown in the Table. A total of 56/58 (96.6%) of neonates had a 5-minute Apgar score ≥7 and 14/88 (15.9%) were admitted to a neonatal intensive care unit. Follow-up beyond the neonatal period was available for 28 neonates (median 42 months, range 1-228), of which reported adverse events were: cardiac abnormality (n=1), speech disorder (n=1), renal disfunction (n=1), and femoral anteversion (n=1). Conclusion: The use of taxane-containing chemotherapy during pregnancy does not seem to increase the risk of obstetric and neonatal complications. Our findings support the use of taxanes during gestation when clinically indicated. Table 1. Reported adverse events with gestational use of taxane-containing chemotherapy regimens. Citation Format: Ana Ferrigno Guajardo, Bryan Vaca-Cartagena, Erica Mayer, Chayma Bousrih, Oluchi Oke, Cristina Saura, Fedro Alessandro Peccatori, Wendy Muñoz-Montaño, Alvaro Cabrera-Garcia, Matteo Lambertini, Luis Corrales, Andrea Becerril-Gaitan, Tal Sella, Alexandra Newman, Barbara Pistilli, Ashley Martinez, Carolina Ortiz, Laia Joval-Ramentol, Giovanna Scarfone, Barbara Buonomo, Fernando Lara-Medina, Jacqueline Sanchez, Luca Arecco, Allan Ramos-Esquivel, Snezana Susnjar, Gilberto Morgan, Cynthia Villarreal-Garza, Hatem Azim. Safety of taxane chemotherapy for the treatment of breast cancer during pregnancy: an international cohort 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 PS13-03.

Thoracic aorta injury detected by 4D flow MRI predicts subsequent main adverse cardiovascular events in breast cancer patients receiving anthracyclines: A longitudinal study

PurposeTo investigate longitudinal thoracic aorta injury using 3-dimensional phase-contrast magnetic resonance imaging (4D flow MRI) parameters and to evaluate their value for predicting the subsequent main adverse cardiovascular events (MACEs) in breast cancer patients receiving anthracyclines. MethodsBetween July 2020 and July 2021, eighty-eight female participants with breast cancer scheduled to receive anthracyclines with or without trastuzumab prospectively enrolled. Each subjects underwent 4D flow MRI at baseline, 3 and 6 months in relation to baseline. The diameter, peak velocity (Vpeak), wall shear stress (WSS), pulse wave velocity (PWV), energy loss (EL) and pressure gradient (PG) of thoracic aorta were measured. The association between these parameters and subsequent MACEs was performed by Cox proportional hazard models. ResultsTen participants had subsequently MACEs. The Vpeak and PG gradually decreased and the WSS, PWV and EL progressively increased at 3 and 6 months compared with baseline. Adjusted multivariable analysis showed that the WSS of the proximal, mid- and distal ascending aorta [HR, 1.314 (95% confidence interval (CI): 1.003, 1.898)], [HR, 1.320 (95% CI: 1.002, 1.801)] and [HR, 1.322 (95% CI: 1.001, 1.805)] and PWV of ascending aorta [HR, 2.223 (95% CI: 1.010, 4.653)] at 3 months were associated with subsequent MACEs. Combined WSS and PWV of ascending aorta at 3 months yielded the highest AUC (0.912) for predicting subsequent MACEs. ConclusionCombined WSS and PWV of ascending aorta at 3 months is helpful for predicting the subsequent MACEs in breast cancer patients treated by anthracyclines.

Rate of adverse cardiovascular events in breast cancer patients receiving chemotherapy and targeted therapy: Impact of frailty

Rate of adverse cardiovascular events in breast cancer patients receiving chemotherapy and targeted therapy: Impact of frailty

Convolution Neural Network-Based Automatic Scoring of Coronary Artery Calcification and Its Value to Identify the Risk of Radiation-Induced Cardiac Toxicity on Radiotherapy Planning CT Scans in Breast Cancer Patients

To develop an automatic scoring of coronary artery calcification (CAC) on breast cancer radiotherapy (RT) planning computed tomography (CT) scans, and to explore its predictive value of CAC for radiation-induced cardiac toxicity. Planning CT scans of 668 breast cancer patients from two prospective clinical trials (NCT02942615, NCT03829553) were retrospectively reviewed. In total, 34 CTs containing CAC were identified. The training and test samples were 29 and 5, respectively. We proposed a two-stage model for CAC segmentation task with nnU-Net as backbone. The segmentation results were processed by threshold extraction and region growth algorithm. We also employed transfer learning to automatically identify calcification of left anterior descending artery (LAD), right coronary artery (RCA), left circumflex artery (LCX), and left main coronary artery (LM) based on a public dataset of 430 cases from Stanford University. The data of cardiac examination of these 34 patients before and during the follow-up after RT were collected. The cardiac event was any symptomatic heart disease or new-onset abnormality in the cardiac examination after RT. The mean dice coefficients (DSC) and 95% Harsdorf distance (95HD) of test samples were 0.992 and 0.599 mm, respectively. The mean absolute error (MAE) of CAC Angaston score between ground truth (GT) and predictions was 0.532. The detailed consistency parameters of 5 test samples were shown in Table 1. After 1:2 propensity score matching (PSM), 21 patients had CAC and 42 patients had no CAC were selected. The number of patients with CAC scores of 1 to 10, 11 to 100, and greater than 100 was 10, 9 and 2, respectively. During median follow-up of 9.2 months (range, 1-42.7), 90.5% and 38.1% of patients in CAC cohort and no CAC cohort developed cardiac event (p<0.001). Patients with CAC had significantly increased cardiac events (HR = 2.4; 95% CI, 1.22-4.75; p = 0.0117). The risk of cardiac events increased with CAC scores ([HR]1-10 = 2.1, 95% CI 0.9-4.9; [HR]11-100 = 2.5, 95% CI 1.0-5.9; [HR]>100 = 4.0, 95% CI 0.9-17.4). Our primary results showed that this two-stage segmentation model is capable of achieving automatic CAC scoring which might assist to predict the risk of post-RT cardiac events in breast cancer patients.

Comparison of adverse effects of anti-tumor therapy for breast cancer shortly after COVID-19 diagnosis vs. the control period.

COVID-19 is an acute infectious disease caused by SARS-CoV-2. The best time to restart antitumor therapy in breast cancer patients after SARS-CoV-2 infection is unknown. This study aimed to evaluate treatment-related adverse events in breast cancer patients who received antitumor therapies within a short time after SARS-CoV-2 infection (observation) as well as before (control) and to provide safety data. We conducted a self-controlled cohort study using the data from the Breast Disease Center of Peking University First Hospital. We identified patients who received antitumor therapy within 28 days after COVID-19 infection between December 20, 2022, and January 20, 2023. The primary outcome was treatment-related adverse events. McNemar's test was used to compare the incidence rate of adverse reactions between periods. We identified 183 patients with breast cancer, of whom 109 were infected with SARS-CoV-2 within 28 days before antitumor treatment and were included. In total, 28 patients (25.7%) received neoadjuvant therapy, 60 (55.0%) received adjuvant therapy, and 21 (19.3%) received advanced rescue therapy. None of patients required hospitalization for severe or critical COVID-19, but 15 patients (13.8%) still had sequelae of COVID-19 while receiving antitumor treatment. The most common adverse events were peripheral neuropathy (n = 32 [29.4%]), pain (n = 29 [26.6%]), fatigue (n = 28 [25.7%]), nausea (n = 23 [21.1%]), and neutropenia (n = 19 [17.4%]). There was no increased risk of overall treatment-related adverse events (n = 87 [79.8%] vs. n = 91 [83.5%]; p = 0.42) or serious adverse events (n = 13 [11.9%] vs. n = 12 [11.0%]; p = 1.00) from receiving antitumor therapy shortly after the diagnosis of COVID-19. We also found no increased risk in subgroup analyses, and no patients discontinued antitumor therapy due to adverse events. Restarting antitumor therapy 2-4 weeks after having mild or moderate COVID-19 is a relatively safe strategy for breast cancer patients that does not increase the risk of treatment-related adverse events.

Adherence to statins and risk of cardiovascular disease in patients with breast cancer.

e24065 Background: Adherence to clinician prescribed cardiovascular disease (CVD) medications is poor in breast cancer (BC) survivors who are at heightened risk of CVD. Information on the effect of nonadherence to lipid-lowering medications on CVD risk in BC survivors is limited. We assessed adherence to statins, common lipid-lowering drugs, and their association with risk of CVD events in BC patients with dyslipidemia in the Kaiser Permanente Northern California (KPNC) integrated health system. Methods: Data were extracted from KPNC electronic health records (EHR). We identified 4,776 stage I-III BC patients diagnosed between 2005-2013 who were alive 6 months post-BC diagnosis (index date), and had a dyslipidemia diagnosis at the time of BC diagnosis along with ≥1 prior outpatient order or dispensing for a statin in the 30 months before index date. Incident heart failure (HF), ischemic heart disease (IHD), and stroke were determined via EHR and validated diagnosis and procedure codes. Statin adherence was assessed using drug dispensing data and updated quarterly starting on the index date to calculate cumulative average adherence (CAA). Working marginal structural models (MSM) fitted with inverse probability weighting were used to evaluate the effect of statin adherence regimens on the hazards for each of the CVD events, while controlling for baseline and time-varying CVD clinical risk factors, BC tumor characteristics, cancer treatments, other lipid-lowering drugs, and socioeconomic status. We considered two MSM parameterizations for two CAA categorizations: poor CAA &lt; 80% vs. good CAA≥80% (ref); and poor CAA &lt; 80% vs. 80%≤good CAA &lt; 100% vs. perfect CAA = 100% (ref). Results: Women were on average 67 years old with BMI of 30 kg/m2 and 65% non-Hispanic white. Over a mean follow-up of 6.5 years, 420 HF, 360 IHD, and 170 stroke events occurred. Overall, poor statin adherence was associated with higher risk of HF, IHD, and stroke combined: CAA &lt; 80% (HR = 2.54; 95% CI: 1.09, 5.94) vs. CAA≥80%. Separately, compared with CAA≥80%, poor statin adherence was associated with a non-statistically significant higher risk of IHD alone, CAA &lt; 80% (HR = 2.69; 95% CI: 0.85, 8.52) and stroke alone, CAA &lt; 80% (HR = 8.13; 95% CI: 2.03, 32.51). Poor adherence was not associated with risk of HF alone, CAA &lt; 80% (HR = 1.03; 95% CI: 0.31, 3.48) vs. CAA≥80%. When examining dose response of adherence, compared with perfect adherence (CAA≥100%), good adherence (80%≤CAA &lt; 100%) was associated with lower risk (HR = 0.35; 95% CI: 0.13, 0.92) while poor adherence (CAA &lt; 80%) was associated with higher risk of any CVD event (HR = 2.45; 95% CI: 1.05, 5.70). Conclusions: Maintaining good adherence (at least 80%) to statins after BC treatment is overall beneficial for cardiovascular health in patients with dyslipidemia. However, unmeasured confounding cannot be ruled out in our study. Future studies should determine factors associated with lower adherence and ways to improve adherence.

Opioid prescriptions at the point of surgery, bone metastasis, or death among patients with breast cancer in Japanese acute care hospitals: a claims-based, retrospective, longitudinal study

PurposeBreast cancer is the most common cancer among Japanese women and often yields a better prognosis than other cancers. However, few studies have been conducted on pain control using opioids in Japan. In this study, we aimed to examine actual opioid use among breast cancer patients.MethodsBreast cancer patients were defined as female patients with a first breast cancer diagnosis during the observational period in an acute care hospital database (April 2008 − February 2020). We examined the percentage of patients prescribed opioids, the opioid amount per patient, and the opioid dosage per day around surgery, bone metastasis diagnosis, or death.ResultsOverall, 217,722 breast cancer patients were identified. The percentage of patients prescribed opioids and the average amount of opioids per patient were highest in the month of surgery, 78% and 27 morphine milligram equivalents (MMEs), respectively. The average opioid dosage increased with time after surgery from 19 to 28 MMEs. Around bone metastasis, the percentage of patients prescribed opioids and the average opioid amount per patient peaked one month after the diagnosis, 31% and 371 MMEs, respectively. The average opioid dosage gradually increased from 22 to 35 MMEs in succeeding days after a bone metastasis diagnosis. The percentage of patients prescribed opioids and the average opioid amount per patient increased as the month of death approached.ConclusionWe investigated opioid prescription trends around clinical events in breast cancer patients on a large scale in Japan. These results may be useful to control cancer pain among breast cancer patients.

Abstract P4-04-01: Safety and efficacy of cryotherapy in the prevention and treatment of chemotherapy-induced peripheral neuropathy in breast cancer patients

Abstract Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a serious clinical problem that can be caused by some cytotoxic agents used in breast cancer (BC) treatment, most commonly seen following taxane-based therapy[1,2]. Several strategies have been studied for CIPN prevention and treatment, but, still, there is no standard recommendation, options are limited and results unsatisfactory [1]. Cryotherapy is a technique that consists of reducing the blood flow in a certain area of the body by cold temperatures, in order to limit the cytotoxic reach. A few studies have been conducted to analyze the safety and efficacy of this strategy in CIPN prevention and treatment, and results are controversial [3,4,5]. More data is needed to clarify cryotherapy role in this clinical context. Methods This is a retrospective analysis of 40 BC patients treated at a single Brazilian institution between December 2019 and June 2022, aiming at efficacy and safety of cryotherapy in the prevention and treatment of CIPN. Cryotherapy was administered by the Hilotherm Clinic Chemo HT02 device (Hilotherm GmbH - Oberwil bei Zug, Switzerland [6]). The procedure consisted of patients using glove and sock-like devices on hands and feet throughout the chemotherapy infusion. The devices were pre-cooled to 10oC and then put on patients 30 minutes before starting, till one hour after the end of chemotherapy infusion. A questionnaire, as proposed by Leonard et al [7], was administered to patients every cycle to assess the development and severity of CIPN symptoms. Statistical analyses were performed by using a Cox regression model. Results Of the 40 patients analysed, 33 (83.5%) underwent a taxane-based regimen. The median number of cryotherapy sessions was three (ranging from 1 to 12), and, when excluded patients who underwent only one session of cryotherapy, the median was 4 (range 2 to 12). 75% of the 40 patients underwent cryotherapy in all chemotherapy sessions, or were still receiving chemo with cryotherapy by the time of our analysis. 80% of those who left treatment did so after the first session (HR 40.44 (CI95: 8.34 – 196.1; p&amp;lt; 0.0001). CIPN was stable or better than the baseline status for 26 (87%) of the 30 patients that underwent more than 1 session of cryotherapy; only 1 (25%) of the four patients who developed CIPN worse than the baseline status had grade 2 symptoms. Conclusion Cryotherapy is a safe and tolerable strategy that can be used during chemotherapy for breast cancer. Our data suggests that this is an efficient approach to prevent and treat CIPN, but the retrospective nature of the study and the small sample size must be considered when interpreting the results. Finally, strategies must be developed to further improve adherence and tolerability, and prospective randomized trials are needed to confirm the efficacy of cryotherapy in this context. 1. Loprinzi et al. Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update. J Clin Oncol 38:3325-3348. 2020 2. Rivera et al. Chemotherapy-Associated Peripheral Neuropathy in Patients With Early-Stage Breast Cancer: A Systematic Review. JNCI J Natl Cancer Inst, 2018, Vol. 110, No. 2 3. Rosenbaek et al. Effect of cryotherapy on dose of adjuvant paclitaxel in early-stage breast cancer. Supportive Care in Cancer (2020) 28:3763–3769 4. Ruddy et al. Randomized controlled trial of cryotherapy to prevent paclitaxel-induced peripheral neuropathy (RU221511I); an ACCRU trial. The Breast Volume 48, December 2019 5. Shigematsu et al. Cryotherapy for the prevention of weekly paclitaxel-induced peripheral adverse events in breast cancer patients. Support Care Cancer. 2020 6. https://www.hilotherm.com/en/about-hilotherm/ accessed on July 15 2022 at 23:03 7. Leonard et al. Survey of oxaliplatin-associated neurotoxicity using an interview-based questionnaire in patients with metastatic colorectal cancer. BMC Cancer 2005, 5:116 Citation Format: Rafael B. Costa, Angélica Nogueira-Rodrigues, Claynner Paccely Oliveira Bessa, Rafaela Cristina Adalberto Menezes, Fernanda Coelho de Miranda Jorge Oliveira, Matheus Costa e Silva, Flávia Rocha Paes, Bruno L. Ferrari. Safety and efficacy of cryotherapy in the prevention and treatment of chemotherapy-induced peripheral neuropathy in breast cancer patients [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 P4-04-01.

Venous thromboembolism incidence in postoperative breast cancer patients

BackgroundVenous Thromboembolism (VTE) is an important cause of morbidity in cancer patients. Breast cancer patients undergoing surgical treatment are at an increased risk of VTE. The aim of this study was to determine the frequency of VTE in patients who underwent surgery for the treatment of breast cancer and to identify the related risk factors. MethodsA historical cohort of patients at the São Paulo State Cancer Institute (ICESP) underwent surgery for breast cancer. The inclusion criteria covered patients with invasive breast cancer or ductal carcinoma in situ who had breast surgery anytime from January 2016 to December 2018. ResultsOf the 1672 patients included in the study, 15 had a confirmed diagnosis of VTE (0.9%), and 3 of these had deep vein thrombosis (0.2%), and 12, had pulmonary thromboembolism (0.7%). Clinical and tumoral characteristics did not differ between the groups. The incidence of VTE was higher in patients who had undergone skin-sparing mastectomy or nipple-sparing mastectomy (p = 0.032). Immediate reconstruction, particularly with abdominal-based flaps (4.7%), increased VTE events (p = 0.033). Median surgical time was higher in patients with VTE episodes (p = 0.027), and total hospital length of stay increased in days (6 days vs. 2 days, p = 0.001). Neoadjuvant chemotherapy and postoperative prophylaxis with Low Molecular Weight Heparin (LMWH) were associated with lower VTE rates (0.2% vs. 1.2%, p = 0.048 and 0.7% vs. 2.7%, p = 0.039; respectively) in these patients. ConclusionsThe incidence of VTE events in breast cancer patients who underwent surgery was 0.9%. Immediate reconstruction (especially with abdominal-based flaps), skin-sparing/nipple-sparing mastectomies, and longer surgeries were associated with increased risk. The LMWH postoperative prophylaxis reduced this risk.

Analysis of the complications of endocrine therapy with tamoxifen in breast cancer: clinical and pharmacogenetic aspects. Prospective pharmacogenetic cohort study

Background. Tamoxifen is the drug of choice in ER-positive breast cancer (BC) therapy for perimenopausal women and one of the endocrine therapy options for menopausal patients. The pharmacological effect of tamoxifen can be influenced by the activity of cytochrome P450 (CYP) enzymes and P-glycoprotein transporters (Pg), and the genes encoding them have broad polymorphism, affecting serum concentrations of active metabolites. This article presents the overall results of a prospective population-based study of the clinical significance of genetic polymorphism of tamoxifen metabolic enzymes and transporters in breast cancer patients after radical treatment receiving adjuvant endocrine therapy with tamoxifen in outpatient settings during 2018-2019. The study was approved by the Research Ethics Committee of the Russian Medical Academy of Continuing Professional Education.&#x0D; Aim. To analyze the clinical presentation of endocrine therapy with tamoxifen in the adjuvant regimen and to assess the association of polymorphisms of genes encoding cytochrome P450 enzymes and drug transporter proteins with adverse events in BC patients.&#x0D; Materials and methods. One hundred and four women with stage I-III luminal breast cancer receiving adjuvant tamoxifen were examined for the presence of CYP2D6, CYP2C, and the following CYP3A gene polymorphisms: CYP2D6*4, CYP3A5*3, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, as well as the ABCB1 gene polymorphic marker (C3435T) encoding the P-glycoprotein. The allelic variants were identified using the real-time polymerase chain reaction; the test was performed in the Research Center of the Russian Medical Academy of Continuing Professional Education. The study material was buccal epithelium (double sampling) taken after informed consent signing.&#x0D; Results. Association analysis showed the association of different genetic polymorphisms of CYP2D6, CYP3A5, CYP2C9, and ABCB1 with tamoxifen adverse drug reactions, indicating the clinical significance of these polymorphisms.&#x0D; Conclusion. With the implementation of genetic testing of the studied polymorphisms into the routine clinical practice of oncologists prescribing tamoxifen and gynecologists involved in the follow-up of breast cancer patients receiving endocrine therapy in the adjuvant mode, there will be an opportunity for more effective and safer pharmacotherapy.

Effect of erythropoiesis-stimulating agents on breast cancer patients: a meta-analysis.

Erythropoiesis-stimulating agents (ESAs) have been reported to increase the risk of death in cancer patients. In this study, we selected breast cancer, which is currently the most prevalent cancer worldwide, for a meta-analysis to re-examine the advantages and disadvantages of using ESAs. All relevant studies were searched by PubMed, Embase, Web of science, and Cochrane Library. Endpoints including mortality, incidence of thrombo-vascular events, hemoglobin, and transfusion requirements were meta-analyzed based on random-effects model or fixed-effect model. 10 studies were finally included, with a total sample size of 6785 patients. The risk of mortality was higher in patients using ESA than in controls (RR 1.07, 95% CI 1.01-1.13, P = 0.03); subgroup analysis found that the mortality rate was higher in patients treating with ESA for > 6months (RR 1.27, 95% CI 1.05-1.55, P = 0.01) and epoetin α (RR 1.07, 95% CI 1.01-1.14, P = 0.03). The incidence of thrombo-vascular adverse events was higher in patients using ESA than in controls (RR 1.53, 95% CI 1.27-1.86, P < 0.0001). The ESA group was more effective in improving anemia in cancer patients (MD 1.20, 95% CI 0.77-1.63, P < 0.00001). The blood transfusion needs of patients in the ESA group were significantly lower (RR 0.52, 95%CI 0.44-0.60, P < 0.00001). There was no statistically significant difference between the two groups in disease progression-related conditions (HR 1.03, 95%CI 0.95-1.12, P = 0.52). ESAs increase the risk of mortality and the incidence of thrombo-vascular adverse events in breast cancer patients, while reducing their anemia symptoms and transfusion requirements. Registration PROSPERO CRD42022330450.

Cardiac Events in Breast Cancer Patients Treated with Modern Radiotherapy

<h3>Purpose/Objective(s)</h3> To characterize cardiac events in a large cohort of breast cancer patients treated with curative radiation therapy at our institution from 2006-2017. Recent reports of cardiac toxicity have primarily been limited to ischemic events. Our hypotheses were that (1) multiple classes of cardiac events would be observed, including ischemic, arrhythmia, cardiomyopathy, pericardial, and valvular events, and (2) toxicity would decrease as modern RT techniques evolved during the study period. <h3>Materials/Methods</h3> Baseline patient characteristics, comorbidities, tumor characteristics, surgical, RT, and systemic treatment were recorded. RT volumes included accelerated partial breast, whole breast, or breast/chest wall and nodal RT. Techniques included 3D-CRT, IMRT, brachytherapy, protons, with prone and deep inspiration breath hold techniques also introduced during the study period. Cardiac events were categorized by class (ischemic, arrhythmia, cardiomyopathy, pericardial, and valvular), as well as by grade (1-5) based on CTCAE and American College of Cardiology criteria. <h3>Results</h3> 3,435 breast cancer patients received adjuvant RT at our institution during this time period and were therefore included in the analysis. Median follow up for cardiac events was 96 months. Mean age at diagnosis was 57 years old and 70% of patients were postmenopausal. 71% were Caucasian, 26% African American, 2% Asian, 1% other. At baseline, 14% of patients had diabetes, 47% hypertension, 24% hyperlipidemia, and 11% had history of a cardiac event prior to treatment. Systemic therapy included endocrine therapy (66%), any chemotherapy (49%), anthracycline (25%) and Herceptin (11%). Incidence of cardiac events was 15% overall. Events by class were 4.5% cardiomyopathy, 3.6% ischemic, 7.0% arrhythmia, 1.8% pericardial, and 5.0% valvular. Patients with history of cardiac events prior to treatment had a greater risk of new events compared to those without pre-existing disease (p <0.01, RR 2.8). Incidence of Grade 1 events was 2.3%, Grade 2 was 7.2%, Grade 3 was 3.2%, and Grade 4 was 2.2%. Incidence of events by year of RT were 22% (2006-2007), 19% (2008-09), 17% (2010-11), 15% (2012-13), 12% (2014-15), and 12% (2016-17). Logistic regression found a significant decrease in cardiac events over time (p < 0.001). Median interval from RT to cardiac event was 45 months (all events), 41 mos (cardiomyopathy), 47 mos (ischemia), 53 mos (arrhythmia), and 45 mos (pericardial). <h3>Conclusion</h3> Incidence of cardiac events were overall fairly low, but not uncommon when all event classes were recorded. Incidence of events was lower in patients treated later in the study period, which may be due to introduction of further advances in RT for breast cancer patients over time. Although patients treated earlier have potential for longer follow up, the median interval to cardiac event was less than the median follow up for the cohort, so these findings will likely be observed with further follow up.

Clinical features and prognostic factors of breast cancer in young women: a retrospective single-center study.

This research aims to characterize the differences in clinical features and prognostic factors between younger and older breast cancer (BC) patients in China. All patients who were recently diagnosed with BC between January 1, 2015 and December 31, 2016 at Shanxi Province Cancer Hospital were recruited. We collected the epidemiological and clinical data as well as the follow-up information. Out of the 1968 BC patients who met the criteria for analysis, 227 (11.53%) were under 40years of age with a median age of 34years at diagnosis. All patients were classified into the age < 40, age 40-59, and age ≥ 60 groups. There were significant differences in the histology, tumor size, T stage, grade, and human epidermal growth factor receptor-2 (HER-2) levels among the three groups (all P < 0.05). The 5-year overall survival (OS) rates were 86.34%, 89.58%, and 84.84% for the age < 40, age 40-59, and age ≥ 60 groups, respectively. The TNM stage was the only predictor of clinical outcome in all BC patients. The prognostic value of intrinsic subtypes for OS was different among the three groups. Our study helped identify an age-related prognostic indicator of adverse events in BC patients and showed that young women with BC exhibited more aggressive clinical and pathological features. Our findings may facilitate clinical management and therapeutic interventions in young BC patients, especially in young women with a history of exposure to risk factors and age < 40years.

A nested case-control study on radiation dose-response for cardiac events in breast cancer patients in Germany

BackgroundPrevious studies with the majority of breast cancer (BC) patients treated up to 2000 provided evidence that radiation dose to the heart from radiotherapy (RT) was linearly associated with increasing risk for long-term cardiac disease. RT techniques changed substantially over time. This study aimed to investigate the dose-dependent cardiac risk in German BC patients treated with more contemporary RT. MethodsIn a cohort of 11,982 BC patients diagnosed in 1998–2008, we identified 494 women treated with 3D-conformal RT who subsequently developed a cardiac event. Within a nested case-control approach, these cases were matched to 988 controls. Controls were patients without a cardiac event after RT until the index date of the corresponding case. Separate multivariable conditional logistic regression models were used to assess the association of radiation to the complete heart and to the left anterior heart wall (LAHW) with cardiac events. ResultsMean dose to the heart for cases with left-sided BC was 4.27 Gy and 1.64 Gy for cases with right-sided BC. For controls, corresponding values were 4.31 Gy and 1.66 Gy, respectively. The odds ratio (OR) per 1 Gy increase in dose to the complete heart was 0.99 (95% confidence interval (CI): 0.94–1.05, P = .72). The OR per 1 Gy increase in LAHW dose was 1.00 (95% CI: 0.98–1.01, P = .68). ConclusionsContrary to previous studies, our study provided no evidence that radiation dose to the heart from 3D-conformal RT for BC patients treated between 1998 and 2008 was associated with risk of cardiac events.

Dapagliflozin associated to sacubitril/valsartan and relationship with cardioprotection in human cardiac cells exposed to doxorubicin and HER2-blocking agents through MyD88, NLRP3 mediated pathways.

587 Background: The cumulative incidence of cardiac events in breast cancer patients treated with anthracycline and trastuzumab at 1 year after the diagnosis of cancer was 16.4%, at 2 years 23.8 %, and at 3 years 28.2%. Sodium glucose co-transporter 2 inhibitors, a new class of antidiabetic drugs, has shown measurable benefits in reduction of HF hospitalization and cardiovascular mortality. LCZ696 (neprilysin inhibitor + valsartan) as able to lower the risk of cardiovascular events in chronic heart failure. We hypothesize that dapagliflozin associated to LCZ696 could exerts cardioprotective effects in cellular models of doxorubicin and trastuzumab-induced cardiotoxicity. Methods: Human cardiomyocytes (HL-1 cells) were exposed to subclinical concentration of doxorubicin and trastuzumab (100 nM) alone or in combination with dapagliflozin (50 nM) or LCZ696 (at 100 mM) or both in combination for 48h. Cell viability, apoptosis and necrosis were performed. Quantification of malondialdehyde, 4-hydroxynonenal and intracellular Ca2+ were performed through spectrophotometric methods. Anti-inflammatory studies were also performed (expression of NLRP3 inflammasome, TLR4/MyD88 pathways, nuclear expression of NF-kB). Intracellular concentration of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF were also performed. Results: Dapagliflozin and LCZ696 increased synergistically the cell viability during exposure to doxorubicin and trastuzumab. Combination of dapagliflozin and LCZ696 reduces intracellular Ca2+ overload (-68,4% vs cells treated only to anticancer drugs; p&lt;0,001), lipid peroxidation (mean reduction of 57-63,4 % compared to cells exposed only to anticancer drugs; p&lt;0,05). The expression of MyD88, NLRP3 and NF-kB were strongly reduced after treatment with dapagliflozin and LCZ-696 (-52,5, -43,7 and -57,3 % vs cells exposed only to anticancer drugs, respectively; p&lt;0.05). Notably, combination of dapagliflozin and LCZ-696 enhanced the expression Of IL-10; contrary, pro-inflammatory cytokines were reduced, such as IL-1α, IL-1β, IL-6, IL-8, IL17-α and IL-18 (p&lt;0.05). Conclusions: During exposure to doxorubicin and trastuzumab, dapagliflozin associated to LCZ-696 exerts additive cardioprotective and anti-inflammatory effects compared to each drug alone. Their properties are mediated by the reduction of iCa2+ content that consequently reduces peroxidation and NLRP3- MyD88 expression. These results indicating the potential use of SGLT-2 inhibitors associated to LCZ696 in preclinical models of cardiotoxicity.

P221 DAPAGLIFLOZIN ASSOCIATED TO SACUBITRIL/VALSARTAN EXERTS ADDITIVE CARDIOPROTECTION IN HUMAN CARDIOMYOCYTES EXPOSED TO DOXORUBICIN AND TRASTUZUMAB THROUGH MYD88, NLRP3 MEDIATED PATHWAYS AND IMPROVEMENT OF MYTOGENESIS

Abstract Introduction The cumulative incidence of cardiac events in breast cancer patients treated with anthracycline and trastuzumab at 1 year after the diagnosis of cancer was 16.4%, at 2 years 23.8 %, and at 3 years 28.2%. Sodium glucose co–transporter 2 inhibitors showed measurable benefits in reduction of HF hospitalization and cardiovascular mortality. LCZ696 (neprilysin inhibitor + valsartan) as able to lower the risk of cardiovascular events in chronic heart failure. Purpose We hypothesize that dapagliflozin associated to LCZ696 could exerts cardioprotective effects in cellular models of doxorubicin and trastuzumab–induced cardiotoxicity Methods Human cardiomyocytes (HL–1 cells) were exposed to subclinical concentration of doxorubicin and trastuzumab (100 nM) alone or in combination with dapagliflozin (50 nM) or LCZ696 (at 100 mM) or both in combination for 48h. Cell viability, apoptosis and necrosis were performed. Quantification of MDA– 4–HNE and Ca2+ were performed through spectrophotometric methods. Anti–inflammatory studies were also performed (expression of NLRP3, TLR4/MyD88 pathways, nuclear expression of NF–kB). Intracellular concentration of IL–1α, IL–1β, IL–2, IL–4, IL–6, IL–8, IL–10, IL–12, IL17–α, IL–18, IFN–γ, TNF–α, G–CSF, and GM–CSF were also performed. Results Dapagliflozin and LCZ696 increased synergistically the cell viability during exposure to doxorubicin and trastuzumab. Combination of dapagliflozin and LCZ696 reduces Ca2+ overload (–68,4% vs cells treated only to anticancer drugs; p &amp;lt; 0,001) and MDA (mean reduction of 57–63,4 % compared to cells exposed only to anticancer drugs; p &amp;lt; 0,05). The expression of MyD88, NLRP3 and NF–kB were strongly reduced after treatment with dapagliflozin and LCZ–696 (–52,5, –43,7 and –57,3 % vs cells exposed only to anticancer drugs, respectively; p &amp;lt; 0.05). Notably, combination of dapagliflozin and LCZ–696 enhanced the expression of IL–10. Expression of IL–1α, IL–1β, IL–6, IL–8, IL17–α and IL–18 was reduced (p &amp;lt; 0.05). Mitogenesis was strictly improved also as demonstrated by confocal microscope analysis Conclusion Dapagliflozin associated to LCZ–696 exerts additive cardioprotective and anti–inflammatory effects compared to each drug alone. Their properties are mediated by the reduction of iCa2+ content that consequently reduces peroxidation and NLRP3– MyD88 expression. These results indicating the potential use of SGLT–2 inhibitors associated to LCZ696 in preclinical models of cardiotoxicity.

SP-0348 Risk of acute coronary events in breast cancer patients after radiation therapy - Insights from a biologicallybased model of atherosclerogenesis

SP-0348 Risk of acute coronary events in breast cancer patients after radiation therapy - Insights from a biologicallybased model of atherosclerogenesis

Is conservative management of ductal carcinoma in situ risky?

Nonsurgical management of ductal carcinoma in situ is controversial and little is known about the long-term consequences of this approach. In this study, we aimed to determine the risk of (a) upstaging to invasive carcinoma at excision and (b) ipsilateral breast cancer events in patients who might have been eligible for nonsurgical management of DCIS trials. Data from women aged 20 years or older with a biopsy diagnosis of DCIS between January 1, 2010 to December 31, 2014 were collated. The women underwent biopsy and surgical resection (lumpectomy or mastectomy) and were treated with radiation or endocrine therapy as per treating physicians’ choice. The development of ipsilateral breast cancer events (IBEs) was analyzed in patients with at least 5 years of follow-up after standard of care therapy for DCIS. Subset-analysis was undertaken to identify the incidence of IBEs in patients eligible for nonsurgical management trials. The study population consisted of 378 patients with matched cases of biopsy and surgical excision. The overall upstaging rate to IBC was 14.3 and 12.9% for COMET, 8.8% for LORIS, and 10.7% for LORD trial “eligible” patients. At 5 years of follow-up, ~11.5% of overall and trial eligible patients developed IBEs of which approximately half were invasive IBEs. In conclusion, women with DCIS who would have been eligible for nonsurgical management trials have a significantly high risk of developing ipsilateral breast events within 5 years of diagnosis. Better selection criteria are needed to identify DCIS patients who are at very low risk for the development of IBC.

Long-term follow-up results of intensity-modulated radiotherapy with helicoïdal tomotherapy for non-metastatic breast cancers: Single centre experience

PurposeIntensity-modulated radiotherapy with helical Tomotherapy is a novel radiation therapy technique, which may be beneficial in several features compared to traditional methods. Our aim was to evaluate the local control, overall survival, progression free survival and adverse events in breast cancer patients treated with this new technique. Material and methodsThis is retrospective analysis of patients irradiated with intensity-modulated radiotherapy with helical Tomotherapy. Overall survival and progression free survival curves were plotted with Kaplan-Meier method. We also analysed the overall survival and progression-free survival data by molecular subgroups. Long-term toxicity including skin, cardiac and pulmonary complications were also evaluated. Multivariant logistic regression analysis was performed to determine the predictors of the side effects. ResultsBetween 2009–2015, 179 consecutive patients with 194 treated breasts were irradiated with intensity-modulated radiotherapy with helical Tomotherapy. The median follow-up were 65 months. The overall survival rate was 89.2% (95% confidence interval [95CI]: 83.5–95.4%), while disease-free survival rate was 85.4% (95CI: 80.2–91%). The Human epidermal growth factor receptor 2-positive patients had the best 5-year overall survival data of 95% (95CI: 85.9–100%). Long-term skin toxicity was the most common, seen in a total of 20.7% of the patients. ConclusionIntensity-modulated radiotherapy with helical Tomotherapy could be safely used for adjuvant breast cancer irradiation in patients with complex anatomy and provides favourable long-term prognosis with acceptable late toxicity.

Pertuzumab increases risk of cardiac events in breast cancer patients

Pertuzumab increases risk of cardiac events in breast cancer patients