Related Deaths Research Articles

Real-world effectiveness, safety and immunogenicity of ocrelizumab in turkish multiple sclerosis patients: a single-center experience for 4-year follow-up.

The aim of this study was to evaluate postmarketing ocrelizumab safety and effectiveness in a real-world population with multiple sclerosis (MS) and matching these parameters among MS disease types. This was a retrospective, single-center study with MS patients treated with ocrelizumab. Demographic, clinical characteristics and immunological data were analyzed, including annualized relapse rate (ARR), relapse-free rate, Expanded Disability Status Scale (EDSS), complete blood count parameters, immunoglobulin (Ig) levels, liver function tests (LFT), hepatitis markers and adverse events in the 4-year follow-up. A total of 96 patients, 22 with relapsing-remitting MS (RRMS), 54 with secondary progressive MS (SPMS), and 20 with primary progressive MS (PPMS) who were treated with at least two doses of ocrelizumab between January 2018 and September 2023 were included in the study. Sixty-five (68%) were women and 31 (32%) were men. The mean age was 48.4 ± 11.1years (20-70years). Ninety-three patients were evaluated in the first year, 65 in the second year, 39 in the third year and 24 in the fourth year of treatment. 96% of patients were relapse-free rate in the first year, 91% in the second year, 85% in the third year and 75% in the fourth year. Eighty-six percent of patients were progression free in the 1st year of treatment, 71% in the 2nd year, in 64% in the 3rd year, and in 62% in the 4th year. During the follow-up of the cases, EDSS remained stable in 77% of RRMS patients, improved in 14%, and worsened in 9%; while EDSS remained stable in 65% of SPMS patients with attacks, it improved in 9% and worsened in 26%; while EDSS remained stable in 60% of PPMS patients, worsening was observed in 40%. There is a significant decrease in IgM and IgG values during the follow-up of ocrelizumab therapy (p < 0.001, p = 0.014). There is no significant difference in IgA, lymphocyte and neutrophil values (p = 0.713, p = 0.086, p = 0.999). No significant relationship was found between low serum IgM levels and the risk of developing infection (p > 0.05). Liver function tests was found to be within normal limits in 94% of the patients over a 4-year period. No hepatitis B, C or A infection, hepatitis B reactivation, tuberculosis, HIV infection, malignancy or drug related death occurred during 4-years follow-up. The most common side effect during ocrelizumab treatment is urinary tract infection (29%); others were upper respiratory tract infections (13%), numbness/tingling of the face, trunk, or extremities (8%), insomnia (6%), headache (5%), and soft tissue infections (cellulitis and dental abscess, 2%). Our results show that ocrelizumab reduces the frequency of attacks and prevent the disease progression in RRMS patients, and reducing the disease progression by primarily stabilizing EDSS scores in SPMS with attacks and PPMS. It is thought that the relatively high rates of urinary tract infection detected in this study may be related with advanced stage of the disease. The absence of hepatitis B reactivation, chronic infection or malignancy in the 4-year follow-up of our cases supports the long-term safety of ocrelizumab treatment. Ocrelizumab may be preferred as an effective and reliable treatment of different types of MS due to non-serious side effects.

Active Targeting Hyaluronan Conjugated Nanoprobe for Magnetic Particle Imaging and Near-Infrared Fluorescence Imaging of Breast Cancer and Lung Metastasis.

A major contributing cause to breast cancer related death is metastasis. Moreover, breast cancer metastasis often shows little symptoms until a large area of the organs is occupied by metastatic cancer cells. Breast cancer multimodal imaging is attractive since it integrates advantages from several modalities, enabling more accurate cancer detection. Glycoprotein CD44 is overexpressed on most breast cancer cells and is the primary cell surface receptor for hyaluronan (HA). To facilitate breast cancer diagnosis, we report an indocyanine green (ICG) and HA conjugated iron oxide nanoparticle (NP-ICG-HA), which enabled active targeting to breast cancer by HA-CD44 interaction and detected metastasis with magnetic particle imaging (MPI) and near-infrared fluorescence imaging (NIR-FI). When evaluated in a transgenic breast cancer mouse model, NP-ICG-HA enabled the detection of multiple breast tumors in MPI and NIR-FI, providing more comprehensive images and a diagnosis of breast cancer. Furthermore, NP-ICG-HAs were evaluated in a lung metastasis model. Upon NP-ICG-HA administration, MPI showed clear signals in the lungs, indicating the tumor sites. This is the first time that HA-based NPs have enabled MPI of cancer. NP-ICG-HAs are an attractive platform for noninvasive detection of primary breast cancer and lung metastasis.

A combined intervention strategy to increase linkage to and retention in substance use treatment for individuals accessing hospital-based services: study protocol

BackgroundIn 2020, New Mexico had the highest alcohol related death and the 11th highest drug overdose rate in the U.S. Towards the long-term goal of addressing this public health problem, we are implementing and evaluating an multi-level intervention designed to identify adults at risk of substance use disorder (SUD) and encourage linkage to and retention in treatment. The first level includes equipping the ED and medical inpatient units of a safety-net hospital with a method to screen individuals at risk of a SUD. The second level includes Seeking Safety (SS), a trauma-specific treatment for PTSD and SUD; and pharmacotherapy for SUD. Motivational Interviewing (MI) is used throughout both levels. Using the SPIRIT guidelines and checklist, this study protocol describes the multi-level intervention and the methodology we are using to assess feasibility and effectiveness.MethodsWe are using a Type 1 hybrid implementation design with a non-randomized approach (ISRCTN registration # ISRCTN33100750). We aim to enroll 110 adults (≧18) who screen positive for unhealthy use of alcohol, prescription medications (used nonmedically) and/or illicit drugs. Peer support workers are responsible for screening, using MI to increase engagement in screening and treatment and delivery of SS. Pharmacotherapy is provided by addiction clinical specialists. Treatment is provided post hospital discharge via telehealth to increase access to care. Participants are identified through (1) review of electronic health records for individuals with a chief or secondary complaint or mental health condition relating to alcohol and/or other drug use, (2) referrals from clinical staff and (3) screening in the ED and medical inpatient units. Feasibility is being measured through process data. Effectiveness will be determined by changes in two primary outcomes: (i) PTSD symptom severity; and (ii) substance use.DiscussionOur study will expand on research related to the implementation of treatment strategies for patients presenting at EDs and admitted to medical inpatients units wherein there is a significant window of opportunity to link patients with follow-up behavioral and clinical services for alcohol and/or drug misuse. The challenges associated with implementation and strategies that have been helpful to address these challenges will further inform the field.

Lung cancer clustering by identification of similarities and discrepancies of DNA copy numbers using maximal information coefficient.

Lung cancer is the second most diagnosed cancer and the first cause of cancer related death for men and women in the United States. Early detection is essential as patient survival is not optimal and recurrence rate is high. Copy number (CN) changes in cancer populations have been broadly investigated to identify CN gains and deletions associated with the cancer. In this research, the similarities between cancer and paired peripheral blood samples are identified using maximal information coefficient (MIC) and the spatial locations with substantially high MIC scores in each chromosome are used for clustering analysis. The results showed that a sizable reduction of feature set can be obtained using only a subset of locations with high MIC values. The clustering performance was evaluated using both true rate and normalized mutual information (NMI). Clustering results using the reduced feature set outperformed the performance of clustering using entire feature set in several chromosomes that are highly associated with lung cancer with several identified oncogenes.

COVID-19 in the Arab countries: Three-year review

Background Twenty-two Arab countries share a common language, history, and culture. Nevertheless, governmental policies, healthcare systems, and resources differ from one Arab country to another. We have been following Coronavirus (COVID-19) from the beginning in each Arab country. In the present study, we aimed to assess the prevalence of COVID-19 in the Arab world and to compare these findings with other significantly affected countries. Methods Websites of the World Health Organization, World COVID-vaccinations tracker, Worldometer, and Ministries of Health were used to extract COVID-19 data in all Arab countries between the period January 2020 to December 2022. Results All Arab countries had 14,218,042 total confirmed COVID-19 cases, 13,384,924 total recovered cases and 173,544 total related deaths. The trend demonstrated that the third quarter of 2021 recorded the highest death toll and the first quarter of 2022 recorded the highest number of confirmed and recovered cases. Compared to the top 15 affected countries, the Arab world ranked last as it had the lowest overall incidence per million population (PMP) of 31,609. The data on total deaths PMP showed that India had the lowest number of deaths with only 377 cases followed by the Arab world with 386 cases. Conclusions Although the number of confirmed, death, and subsequently recovered cases of COVID-19 have greatly reduced in the last quarter of 2022 in most Arab countries, many Arab countries still need to re-campaign about COVID-19 vaccines and raise awareness programs about boosters. COVID-19 has had a relatively smaller impact on Arab countries than on other countries that have been significantly affected.

An mHealth Intervention for Gay and Bisexual Men's Mental, Behavioral, and Sexual Health in a High-Stigma, Low-Resource Context (Project Comunică): Protocol for a Randomized Controlled Trial.

The World Health Organization reported that 80% of new HIV diagnoses in Europe in 2014 occurred in Central and Eastern Europe. Romania has a particularly high HIV incidence, AIDS prevalence, and number of related deaths. HIV incidence in Romania is largely attributed to sexual contact among gay and bisexual men. However, homophobic stigma in Romania serves as a risk factor for HIV infection for gay and bisexual men. The Comunică intervention aims to provide a much-needed HIV risk reduction strategy, and it entails the delivery of motivational interviewing and cognitive behavioral therapy skills across 8 live text-based counseling sessions on a mobile platform to gay and bisexual men at risk of HIV. The intervention is based on the information-motivation-behavior and minority stress models. There is preliminary evidence suggesting that Comunică holds promise for reducing gay and bisexual men's co-occurring sexual (eg, HIV transmission risk behavior), behavioral (eg, heavy alcohol use), and mental (eg, depression) health risks in Romania. This paper describes the protocol for a randomized controlled trial designed to test the efficacy of Comunică in a national trial. To test Comunică's efficacy, 305 gay and bisexual men were randomized to receive Comunică or a content-matched education attention control condition. The control condition consisted of 8 time-matched educational modules that present information regarding gay and bisexual men's identity development, information about HIV transmission and prevention, the importance of HIV and sexually transmitted infection testing and treatment, heavy alcohol use and its associations with HIV transmission risk behavior, sexual health communication, finding social support, and creating sexual health goals. Participants undergo rapid HIV and syphilis testing and 3-site chlamydia and gonorrhea testing at baseline and the 12-month follow-up. Outcomes are measured before the intervention (baseline) and at the 4-, 8-, and 12-month follow-ups. The study was funded in September 2018, and data collection began in May 2019. The last participant follow-up was in January 2024. Currently, the data analyst is cleaning data sets in preparation for data analyses, which are scheduled to begin in April 2024. Data analysis meetings are scheduled regularly to establish timelines and examine the results as analyses are gradually being conducted. Upon completion, a list of manuscripts will be reviewed and prioritized, and the team will begin preparing them for publication. This study is the first to test the efficacy of an intervention with the potential to simultaneously support the sexual, behavioral, and mental health of gay and bisexual men in Central and Eastern Europe using motivational interviewing support and sensitivity to the high-stigma context of the region. If efficacious, Comunică presents a scalable platform to provide support to gay and bisexual men living in Romania and similar high-stigma, low-resource countries. ClinicalTrials.gov NCT03912753; https://clinicaltrials.gov/study/NCT03912753. DERR1-10.2196/52853.

Direct impact of COVID-19 vaccination in Chile: averted cases, hospitalizations, ICU admissions, and deaths

BackgroundChile rapidly implemented an extensive COVID-19 vaccination campaign, deploying a diversity of vaccines with a strategy that prioritized the elderly and individuals with comorbidities. This study aims to assess the direct impact of vaccination on the number of COVID-19 related cases, hospital admissions, ICU admissions and deaths averted during the first year and a half of the campaign.MethodsVia Chile’s transparency law, we obtained access to weekly event counts categorized by vaccination status and age. Integrating this data with publicly available census and vaccination coverage information, we conducted a comparative analysis of weekly incidence rates between vaccinated and unvaccinated groups from December 20, 2020 to July 2, 2022 to estimate the direct impact of vaccination in terms of the number of cases, hospitalizations, ICU admissions and deaths averted, using an approach that avoids the need to explicitly specify the effectiveness of each vaccine deployed.ResultsWe estimated that, from December 20, 2020 to July 2, 2022 the vaccination campaign directly prevented 1,030,648 (95% Confidence Interval: 1,016,975-1,044,321) cases, 268,784 (95% CI: 264,524-273,045) hospitalizations, 85,830 (95% CI: 83,466-88,194) ICU admissions and 75,968 (95% CI: 73,909-78,028) deaths related to COVID-19 among individuals aged 16 years and older. This corresponds to a reduction of 26% of cases, 66% of hospital admissions, 70% of ICU admissions and 67% of deaths compared to a scenario without vaccination. Individuals 55 years old or older represented 67% of hospitalizations, 73% of ICU admissions and 89% of deaths related to COVID-19 prevented.ConclusionsThis study highlights the role of Chile's vaccination campaign in reducing COVID-19 disease burden, with the most substantial reductions observed in severe outcomes.

Koori Quit Pack: A feasibility study of a multi-component mailout smoking cessation support for Aboriginal and Torres Strait Islander people: "I would recommend it to anybody. It's just so much easier".

Smoking is the leading cause of preventable death among Aboriginal and Torres Strait Islander people. The Koori1 Quit Pack study aimed to assess the feasibility of a multi-component mailout smoking cessation intervention to reduce smoking among Aboriginal and Torres Strait Islander people. A non-randomised, single-group feasibility study conducted among Aboriginal and Torres Strait Islander people who reported current smoking. The intervention package included information pamphlets and resources on quitting, referral offer to Aboriginal Quitline and optional free Nicotine Replacement Therapies (NRT). Follow-up was conducted at 2-weeks, 6-weeks, 10-weeks and 6-months post recruitment. Feasibility outcomes were recruitment and retention rates, uptake of intervention components and smoking abstinence at 6-week follow-up (primary end point). Cessation outcomes were analysed using both a complete case analysis and intention-to-treat approach. 165 participants were recruited, 111 (67.3%), 79 (47.9%), 59 (35.8%), and 94 (57%) participants completed the 2-week, 6-week, 10-week, and 6-month follow-up. At 10-week follow-up, 40.7% of participants used pamphlets and booklets, 13.6% used Quitline and > 90% used NRT. At 6-week follow-up, 87.3% reported a quit attempt and 46.8% sustained quitting. 46.8% were continuously smoke-free at the 6-week timepoint. The complete case analysis and the intention-to-treat analysis at 6-month shows a 7-day self-reported point prevalence abstinence of 34% and 19.4% respectively. The Koori Quit Pack mailout smoking cessation program was feasible to support Aboriginal and Torres Strait Islander people. The intervention resulted in a high smoking cessation rate and should be upscaled, implemented and evaluated nationally. Aboriginal and Torres Strait Islander people are disproportionately impacted by tobacco related harms, however the majority want to quit or wish they never took up smoking. Mailout cessation support is feasible, overcomes access barriers to evidence-based support and increases quitting success. We recommend a national mailout smoking cessation program is implemented for, and by Aboriginal and Torres Strait Islander people to accelerate declines in smoking prevalence to eliminate tobacco related death and disease.

Abstract PO1-29-02: Two and a half years follow-up data of HER2-targeted bispecific antibody KN026 combined with docetaxel as first-line treatment for HER2-positive recurrent/metastatic breast cancer

Abstract Background: KN026 is a novel bispecific HER2-targeted antibody. Fully humanized, IgG1-like antibody binds to two distinct HER2 epitopes, the same domains as trastuzumab and pertuzumab. Preliminary safety and efficacy results (data as of Aug 18, 2022) were presented at SABCs 2022(PD18-08), showed promising efficacy and tolerability. Herein, we update the 2.5-year follow-up results. Methods: Eligible subjects with recurrent/metastatic breast cancer, HER-2 positive and treatment-naive were enrolled. Subjects received KN026 30 mg/kg combined with docetaxel 75 mg/m2 Q3W until disease progression, unacceptable toxicity, or other reasons. The primary endpoints were ORR and DoR. The secondary endpoints included safety, PFS and OS. Results: As of data cut-off date (Sep 15, 2023), 57 subjects were enrolled, the median age was 52 years (min:30, max:67), 100% were female, and 91.2 % (52/57) were stage IV. There were 34 and 23 subjects with and without visceral metastasis, respectively. 48 subjects with high HER2 expression (IHC 3+), and the other 9 subjects with HER2 expression 2+ or 1+. The confirmed ORR within 55 evaluable subjects was 76.4% (42/55). The DoR was not reached yet with a median follow-up of 27.0 mons (95% CI: 26.28, 28.98). The median study follow-up was 30.6 mons (95% CI: 29.11, 31.77). The mPFS was 27.7 mons (95% CI:17.97, NE) and the mOS was not reached. The OS rates at 12m, 24m and 30m were 93.0% (95% CI: 82.37, 97.31), 84.2% (95% CI: 71.85, 91.45) and 78.5% (95% CI: 65.25, 87.21). The mPFS of subjects with or without visceral metastasis were 23.6 mons and not reached. The mPFS of subjects with or without brain metastasis were 13.7 mons and 28.1 mons, respectively. The mPFS of 48 subjects with high HER2 expression (3+) was 28.1 months. The incidence of KN026-related Grade≥3 TRAE was 43.9% (25/57), including neutrophil count decreased 24.6% (14/57), white blood cell count decreased 12.3% (7/57), hypokalaemia 7.0% (4/57), diarrhoea 3.5% (2/57) and others less than 2%. The incidence of serious adverse events related to KN026 was 12.3% (7/57). There was no KN026 -related death. Conclusions: KN026 in combination with docetaxel is well tolerated and has shown promising clinical benefit as 1L treatment for HER2-positive BC. After 2.5 years follow-up, mPFS was 27.7 mons and the 24-months OS rate was 84.2%, which is very promising. No new safety signals were observed. Robustness of efficacy and safety results will be further confirmed in an ongoing randomized phase 3 clinical trial with PTH as control. Citation Format: Qingyuan Zhang, Jingxuan Wang, Quchang Ouyang, Xiaojia Wang, Jingfen Wang, Lu Gan, Daren Lin, Zhong Ouyang, Ting Xu, Yilan Liu, Yuan Lv. Two and a half years follow-up data of HER2-targeted bispecific antibody KN026 combined with docetaxel as first-line treatment for HER2-positive recurrent/metastatic breast cancer [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 PO1-29-02.

Trends in prevalence, mortality, and risk factors of dementia among the oldest-old adults in the United States: the role of the obesity epidemic.

The oldest-old population, those aged ≥ 80years, is the fastest-growing group in the United States (US), grappling with an increasingly heavy burden of dementia. We aimed to dissect the trends in dementia prevalence, mortality, and risk factors, and predict future levels among this demographic. Leveraging data from the Global Burden of Disease Study 2019, we examined the trends in dementia prevalence, mortality, and risk factors (with a particular focus on body mass index, BMI) for US oldest-old adults. Through decomposition analysis, we identified key population-level contributors to these trends. Predictive modeling was employed to estimate future prevalence and mortality levels over the next decade. Between 1990 and 2019, the number of dementia cases and deaths among the oldest-old in the US increased by approximately 1.37 million and 60,000 respectively. The population growth and aging were highlighted as the primary drivers of this increase. High BMI emerged as a growing risk factor. Females showed a disproportionately higher dementia burden, characterized by a unique risk factor profile, including BMI. Predictions for 2030 anticipate nearly 4 million dementia cases and 160,000 related deaths, with a marked increase in prevalence and mortality anticipated among those aged 80-89. The past 30years have witnessed a notable rise in both the prevalence and mortality of dementia among the oldest-old in the US, accompanied by a significant shift in risk factors, with obesity taking a forefront position. Targeted age and sex-specific public health strategies that address obesity control are needed to mitigate the dementia burden effectively.

Abstract PO2-27-02: Re-sensitizing the Refractory Breast Cancer Bone Metastasis to Endocrine Therapies

Abstract Approximately 90% of Breast Cancer (BrCa) related deaths are caused by metastasis and bone is the first and most frequent site of breast cancer metastatic expansion, which can lead to severe pain, immobility, fractures, and nerve damage, as well as the development of metastases in other organs, hence; a poor quality of life in patients. Currently, treatment options for these bone metastases (BoM) are limited because most patients with BoM shows reduced ER dependency which leads to resistance to standard endocrine or hormonal therapies for estrogen receptor-positive (ER+) BrCa. The long-term goal of the proposed research is to develop a strategy where metastatic cancer cells in bone can be dependent on ER signaling again thereby restoring their sensitivity to endocrine therapies. We observed a transient loss of ER expression in concert with enhanced activity of the transcriptional coactivators YAP/TAZ - the downstream effectors of the Hippo pathway (responsible for regulating cell proliferation and death) during bone colonization by BrCa cells. We hypothesize that the interaction between cancer cells and osteoblasts in the bone microenvironment leads to the activation of calcium signaling in cancer cells, resulting in the de-phosphorylation and nuclear localization of YAP/TAZ which subsequently suppresses the transcription of the estrogen receptor gene (ESR). Our research strategy is as presented below. First, we will employ a combination of 2D/3D co-culture models of BoM along with a mechanical loading system and determine the molecular mechanism driving the dynamical activation of YAP/TAZ in BrCa BoM. Using a unique ex vivo BM model called Bone In Culture Array (BICA) which replicates the in-vivo conditions, we will determine if verteporfin, a YAP/TAZ antagonist, can synergize and possibly enhance the effects of Fulvestrant, an ER antagonist in current use for certain types of BrCa in preventing BoM outgrowths and treating established BoM in mice. This research could ultimately lead to a favorable combination strategy to treat endocrine-resistant BoM in BrCa patients and prolong their survival. Citation Format: Anindita Das, Cheyenne Ernst. Re-sensitizing the Refractory Breast Cancer Bone Metastasis to Endocrine Therapies [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 PO2-27-02.

Abstract PS02-07: Effectiveness of 24-week mobile application based human coaching program for controlling weight, BMI and body composition in overweight/obese breast cancer survivors: Single-arm prospective cohort study

Abstract Background: Overweight/obesity has been known as a prognostic factor for breast cancer recurrence and breast cancer related death. However, weight control is hard in breast cancer survivors because of menopause, chemotherapy, anti-hormonal therapy, and psychologic issues. This study aimed to develop 24-week mobile application based human coaching program with Noom and evaluate its efficacy in overweight/obese breast cancer survivors. Methods In this single-arm prospective cohort study, 130 breast cancer survivors with BMI ≥25 were enrolled and received 24-week program including diet-,exercise-, and psychology-based contents with trained human coach in Noom during 2019-2021. For hyperactive group who joined more than 16 weeks, we evaluated weight, BMI, lipid level, bioimpedance, and Quality of Life (QoL) at baseline, 6 month and 12month follow-up. Results Among 130 breast cancer survivor, 101 participants (77.7%) and 93 participants (71.5%) completed 6 month and 12 month follow-up, respectively. In hyperactive group (68/101, 67%), body weight and BMI reduced significantly (mean difference: -1.97 kg, 95% CI (confidence interval):-2.65- -1.26, P&amp;lt; 0.001 and -0.86, 95% CI:-1.15- -0.56, P&amp;lt; 0.001, respectively) at 6 month and maintained at 12 month without the yo-yo effect. Among the lipid panel, triglycerides level decreased significantly (-34.13, 95% CI:-58.09- -10.17, P=0.006) and maintained at 12 month. In the aspect of bioimpedance components, skeletal muscle mass (SMM, kg), body fat mass (BFM, kg), percent body fat (PBF, %), waist-hip ratio (WHR), and visceral fat area (VFA, cm2) were improved for first 6 months. However, WHR and VFA increased during next 6months. Based on the EORTC QLQ C30 and BR 23, nausea/vomiting, constipation, body image, arm and breast symptoms showed significant improvement during the first 6monts. Conclusions This study demonstrated that 24-week mobile application based human coaching program is beneficial for controlling body weight, BMI, TG and body composition in bioimpedance for overweigh/obsess breast cancer survivors. ClinicalTrials.gov NCT05506189; https://clinicaltrials.gov/ct2/show/ NCT05506189. IRB: NCC2019-0098 Citation Format: So-Youn Jung, Eun-Gyeong Lee, Dong-Eun Lee, Jeongseon Kim, Jai Hong Han, Seeyoun Lee, Han-Sung Kang, Eun Sook Lee, Heejung Chae, Sung Hoon Sim, Keun Seok Lee, Jungeun Lee. Effectiveness of 24-week mobile application based human coaching program for controlling weight, BMI and body composition in overweight/obese breast cancer survivors: Single-arm prospective 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 PS02-07.

Abstract PO1-14-02: Real world application of a 21-gene recurrence score in a Swiss single center breast cancer population. A comparative analysis of treatment administration before and after TAILORx

Abstract PO1-14-02: Real world application of a 21-gene recurrence score in a Swiss single center breast cancer population. A comparative analysis of treatment administration before and after TAILORx

Abstract PO1-25-07: Obesity, breast cancer, and adipose-derived mesenchymal stem/stromal cells: The complex cross-signaling in the tumor microenvironment

Abstract Objective: Breast cancer is the most frequently diagnosed cancer and a common cause of cancer related death in women. The breast cancer microenvironment (TME) is mainly composed of adipose tissue, consisting of adipocytes, adipose-derived mesenchymal stem/stromal cells (bASCs) and immune cells. Interestingly, it is well recognized that obesity, as indicated by increased body mass index (BMI≥30), is associated with an enhanced risk of more aggressive breast cancer (BC) as well as reduced patient survival. Therefore, we asked how BC affects the biological functionality of bASC, how obesity fuels this process, and on the other hand how these cells influence BC cells. Methods: Multiple molecular biological approaches as transcriptomic profiling and diverse functional assays were conducted to characterize at least 5 lean and obese patients derived bASCs samples near the TME (lean/obese-aT) or distant (lean/obese-dT). Afterwards, these cells were used to investigate the interaction with BC cells in 2-dimensional and 3-dimensional cell culture experiments. Moreover, immunohistological analyses were conducted in 16 lean and 16 obese breast cancer patients (grade 3-4). Results: The TME shifts bASCs towards cancer supporting phenotypes into an inflammatory cancer-associated phenotype, whereas ob-aT bASCs are prone to be cancer-educated into a myofibroblastic phenotype with a significant deregulated gene expression, cytokine/chemokine secretion, and reduced differentiation capacity. In corroberation, these BMI dependent de-differentiation processes could be confirmed in breast cancer tissue. Moreover, the cell-cell interaction of BC cells with aT-bASCs increased their proliferation, motility, and chemoresistance. Conclusions: The study found multiple pathways deregulated in bASCs associated with tumor promoting effects. Additionally, it revealed the role of aT-bASCs in promoting breast cancer progression on a functional and molecular level. Citation Format: Andreas Ritter, Christine Solbach, Juping Yuan. Obesity, breast cancer, and adipose-derived mesenchymal stem/stromal cells: The complex cross-signaling in the tumor microenvironment [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 PO1-25-07.

Abstract PO2-04-13: TWT-203: PHASE 1b/2 STUDY OF CFI-402257 AS MONOTHERAPY IN ADVANCED SOLID TUMORS AND IN COMBINATION WITH FULVESTRANT IN PATIENTS WITH ER+/HER2- ADVANCED BREAST CANCER AFTER PROGRESSION ON PRIOR CDK4/6 INHIBITORS AND ENDOCRINE THERAPY

Abstract Background: TTK (Threonine Tyrosine Kinase also known as Monopolar spindle 1), is a dual-specificity serine-threonine kinase critical for anaphase promoting complex inhibition at the spindle assembly checkpoint and is required for chromosome alignment and error correction. TTK inhibition results in premature mitosis exiting with unattached chromosomes potentially leading to aneuploidy and cell death. High TTK tumor levels correlate with worse prognosis and contribute to the survival and proliferation of aneuploid cells. CFI-402257, a potent and selective inhibitor of TTK, inhibits the growth of a variety of human cancer-derived cell lines. A first-in-human phase 1 study of CFI-402257 (NCT02792465) demonstrated a tolerable safety profile when enrolled as a monotherapy in solid tumors, and in combination with fulvestrant in hormone receptor positive, HER2 negative (HR+/HER2-) breast cancer1. The dose for expansion was 168 mg, dose limiting toxicity was dose-dependent neutropenia which was manageable and reversible. Investigator-confirmed partial responses (cPR) were observed in 5 pts (8%) with 32 (50.8%) exhibiting disease control. In the HR+/HER2- breast cancer population previously treated with cyclin dependent kinase 4/6 inhibitors (CDK4/6i) and aromatase inhibitors (N=25), there were 4 cPR’s with a median duration of response of 223 days, with responses emerging after 2 cycles of therapy. Responses were observed with CFI-402257 as a single agent and in combination with fulvestrant. Based on these data, study TWT-203 will focus on advanced solid tumors for dose confirmation then focus on advanced HR+/HER2- breast cancers in combination with an approved endocrine therapy. Methods: In TWT-203 study, safety and clinical activity of CFI-402257 monotherapy will be evaluated in patients (pts) with advanced solid tumors (Part A) or in combination with fulvestrant in pts with HR+/HER2- advanced breast cancer (Part B). Part A will confirm the RP2D using a 3+3 design with a starting dose of 126 mg daily. Part B evaluates CFI-402257 in combination with fulvestrant in pts with HR+/HER2- advanced breast cancer following progression on prior CDK4/6i and endocrine therapy. Efficacy endpoints include overall response rate and disease control rate. Safety endpoints include incidence of treatment emergent adverse events. Exploratory objectives include characterization of protein and molecular alterations relevant to the cell cycle and CFI-402257 response. Results: At data cutoff of 11 May 2023, 14 pts were enrolled. All received monotherapy treatment. Median treatment duration was 2.1 months (range, 0.2-7.3+). Median age was 67 years (57-76). Median number of prior regimens was 3.5 (2-12). Tumor types enrolled were colorectal (n=6, 43%), breast (3, 21%), and endometrial, hepatocellular, leiomyosarcoma, pancreatic, and sarcoma (1 each, 7%). 4 dose levels, from 126 to 252 mg, were studied. Most pts (12, 86%) experienced ≥1 treatment emergent adverse event (TEAE). More than half of pts (8, 57%) experienced ≥1 treatment related TEAE. Most common TEAEs were fatigue (5, 36%) and nausea (4, 29%). 5 pts (36%) experienced TEAEs grade ≥3, most common were fatigue, neutrophil count decrease, white blood cell count decrease (2 pts each, 14.3%). 1 pt (7%) experienced a serious adverse event (hematuria), not related to study therapy. No patients discontinued treatment due to TEAE. All pts who ended treatment were due to disease progression (8, 57%). No grade 5 TEAEs occurred. No dose limiting toxicities were reported. Disease control rate (CR, PR, or SD ≥ 6 weeks from baseline) was 54.5% (6 pts/11): all achieved SD. 3 of the 6 pts remain on study. Conclusion: CFI-402257 is a potent inhibitor of TTK. It is well tolerated with manageable TEAEs, no dose limiting or treatment limiting toxicities, and no treatment related deaths. Dose expansion in the patient population of interest will commence. 1. John Hilton et al. Cancer Res 2023;83(5 Suppl): P6-10-13. Citation Format: Justin Call, Muralidhar Beeram, Alexander I. Spira, Mark Bray, Dih-Yih Chen, Long Kwei, Emily Roberts-Thomson, Trisha Denny, Roger Sidhu, Robert Wesolowski. TWT-203: PHASE 1b/2 STUDY OF CFI-402257 AS MONOTHERAPY IN ADVANCED SOLID TUMORS AND IN COMBINATION WITH FULVESTRANT IN PATIENTS WITH ER+/HER2- ADVANCED BREAST CANCER AFTER PROGRESSION ON PRIOR CDK4/6 INHIBITORS AND ENDOCRINE THERAPY [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 PO2-04-13.

Abstract PO4-16-08: Prognostic factors for tumor recurrence after breast-conserving and radiotherapy treatment for early invasive breast cancer: ten years of results in a referral center in Mexico City

Abstract Background: Breast cancer is the most common malignancy in the world, reporting more than 2 million new cases in 2020. In early stages, patients undergo primary surgery. Breast-conserving surgery (BCS) has generally been accepted as a treatment for invasive breast cancer, findings at 20 years still show that lumpectomy and breast irradiation, as compared with mastectomy, have no significant difference in overall survival among the treatment groups. Approximately 10-15% of patients will develop local or systemic recurrence in 5 to 10 years. Factors such as young age (&amp;lt; 45 years), close/positive margins, no breast radiation, are associated with ipsilateral breast tumor recurrence. High grade has been related to distant metastasis. The mortality trend is upward due to a higher incidence of the disease and earlier detection. Methods: This is an observational and retrospective cohort study, which included patients with early breast cancer, who were treated with conserving surgery and received radiotherapy, at the Breast Oncology Service at the UMAE Gineco 4 "Luis Castelazo Ayala" during the period from January 2012 to December 2022. The aim of our study was to describe the prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in patients with localized breast cancer treated with BCS. DFS was defined as time from surgery to recurrence event (local recurrence, distant recurrence, contralateral breast cancer, second primary cancer, or death from any cause) whichever occurred first. For statistical analysis, Kaplan Meier and Log-rank methods were used for survival analysis. Cox proportional hazard model was used for multivariate analysis. Results: We included 399 patients, the median follow-up was 88 months (95%CI 86-91). Median age was 59 years. The most common pathological stage was IA in 44.9%, the predominant immunophenotype was luminal A in 56.1% of patients, follow by luminal B in 19.3% and 13% were triple negative. Management of axilla with sentinel node biopsy occurred in 50.1% and 49.9% underwent to lymph node dissection. Regarding surgery outcomes 40.4% of the patients required widening of the margins, 5% of the patients remained with close surgical margins ≤2 mm, 7.5% had complications associated with the surgery, and none related death ocurred. All patients received adjuvant radiotherapy, the median time to initiation was 32 weeks (range 3-70) and 65.4% received adjuvant chemotherapy. Recurrence events occurred in 15.5% of patients, local 2.8%, systemic 8.8%, contralateral breast cancer 1.7%, and second primary 2.2%. Estimated disease-free survival at 5 and 10 years were 86.6% and 74.2%, respectively. In the multivariate analysis independent prognostic factors for DFS were: lobular histology HR 2.95 (95%IC 1.5-5.7), tumor size ≥ 2cm HR 1.95 (95%IC 1.1-3.6), close surgical margins HR 2.62 (95%IC 1-6.6), and ER low expression (1-10%) HR 4.39 (95%CI: 1.6-12.4). Estimated OS at 5 and 10 years for patients who experienced recurrence were 78.4% and 47.4% and for patients without recurrence were 96.8% and 93.5%, respectively (adjusted HR: 10.4, 95%CI: 5.2-20.6). Conclusion: These results suggest that patients with early breast cancer treated with conserving surgery and radiotherapy with risk factors such as lobular carcinoma, tumor size ≥2cm, close margins, and low expression of estrogen receptors have a high risk of recurrence and significantly decreased overall survival at 5 and 10 years. Citation Format: Nayeli Ortega-Avila, Yuly A. Remolina-Bonilla, Janett Caballero-Jasso. Prognostic factors for tumor recurrence after breast-conserving and radiotherapy treatment for early invasive breast cancer: ten years of results in a referral center in Mexico City [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 PO4-16-08.

Abstract ED11-01: Is inflammatory breast cancer a genomically different type of breast cancer?

Abstract Inflammatory Breast Cancer (IBC) is a unique and aggressive disease, constituting 2 - 4% of breast cancer diagnoses yet responsible for up to 10% of breast cancer related deaths. IBC remains a clinical diagnosis, without highly specific molecular markers, and the genomic drivers of the disease are incompletely characterized. The overrepresentation of human epidermal growth factor 2 amplification and triple-negative disease within IBC have confounded comparisons between IBC and non-IBC. Nonetheless, some consistent genomic observations have emerged that may begin to explain the characteristic behavior of IBC, supported by both comparative clinical studies and preclinical models. This session will review mutational analysis, gene expression profiling, and epigenetic findings that highlight similarities as well as subtle differences between IBC and non-IBC. Citation Format: F. Howard. Is inflammatory breast cancer a genomically different type of breast cancer? [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 ED11-01.

Abstract PS14-01: Immune related adverse events in patients ≥65 years vs. &amp;lt;65 years with breast cancer treated with immunotherapy

Abstract Background: Pembrolizumab is approved for early/advanced triple negative breast cancer (TNBC), and atezolizumab was previously approved for advanced TNBC. Toxicity of immunotherapy (IO) and immune related adverse events (irAEs) in patients ≥65 years with TNBC is not described in detail in results from registration trials (KEYNOTE 522, KEYNOTE 355, and IMPassion130), where patients ≥65 years were a minority. Understanding real-world IO toxicity and irAEs in patients with breast cancer ≥65 years may inform clinical decision making. Methods: We studied IO toxicity and irAEs in patients with breast cancer ≥65 years vs. &amp;lt; 65 years (at IO start) who received IO at an academic institution. A retrospective review was conducted to identify IO toxicity and irAEs (classified by CTCAE v 5.0). Cohorts were compared with Pearson's chi-squared test (categorical variables) and Wilcoxon rank-sum test (continuous variables). Results: Cohorts had 25 patients ≥65 years (median age 73 years, interquartile range (IQR) 69-74 years) and 104 patients &amp;lt; 65 years (median age 48 years, IQR 39-56 years). Stage I-III/IV breast cancer distribution was 36%/64% for ≥65 years and 68%/32% for &amp;lt; 65 years. Baseline ECOG performance status was mainly 0-1 in both cohorts. IO was mainly pembrolizumab (≥65 years: 96%; &amp;lt; 65 years: 83% for first IO regimen) vs. atezolizumab. Table 1 depicts characteristics of IO toxicity. IO duration was longer in patients &amp;lt; 65 years. While rates of IO interruption for toxicity and discontinuation for toxicity were numerically higher in patients ≥65 years, these findings did not reach statisticial significance, possibly due to the sample size. Similar overall rates of irAEs were seen (≥65 years: 72%; &amp;lt; 65 years: 65%, p=0.47) but there were differences in the types of irAEs. Patients &amp;lt; 65 years had more transaminitis (≥65 years: 12%; &amp;lt; 65 years: 33%, p=0.04), and grade 2-3 hypothyroidism (among patients developing hypothyroidism, ≥65 years: grade 1- 75%, grade 2- 25%, grade 3- 0%; &amp;lt; 65 years: grade 1- 11%, grade 2- 79%, grade 3- 11%, p=0.017). Conversely, patients ≥65 years had higher rates of irAE nephritis (≥65 years: 12%; &amp;lt; 65 years: 1%, p=0.004); notably, none of the patients had baseline chronic kidney disease. Rates of full resolution of irAEs were similar between cohorts (≥65 years: 67%; &amp;lt; 65 years: 57%, p=0.47), but patients ≥65 years had more steroid use for management of first irAE while patients &amp;lt; 65 years required more thyroid hormone supplementation (first irAE management distribution, ≥65 years: steroids- 71%, thyroid hormone- 7%, supportive care- 21%; &amp;lt; 65 years: steroids- 31%, thyroid hormone- 25%, supportive care- 44%, p=0.025). Late onset irAEs and deaths from irAEs were rare in both cohorts, with 1 irAE related death in the cohort ≥65 years. Conclusions: In this real-world cohort, similar overall rates of irAEs were observed in patients ≥65 years and &amp;lt; 65 years. However, patients ≥65 years had higher rates of irAE nephritis and steroid use for irAEs, while patients &amp;lt; 65 years had more transaminitis and higher grade hypothyroidism, requiring more thyroid hormone supplementation. Given these age specific differences, validation in a larger cohort is merited. Table 1. Characteristics of IO toxicity. Citation Format: Neelima Vidula, Jennifer Hutchinson, Abigail McLaren, Lianne Ryan, Andrzej Niemierko, Aditya Bardia. Immune related adverse events in patients ≥65 years vs. &amp;lt;65 years with breast cancer treated with immunotherapy [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 PS14-01.

Abstract PO5-05-08: LOSS OF SINGLEMINDED 2S RESULTS IN A PI3K SUBUNIT SWITCH WHICH DRIVES THERAPEUTIC RESISTANCE IN ESTROGEN RECEPTOR POSITIVE BREAST CANCER

Abstract Estrogen receptor (ER) + breast cancer (BC) comprises over 70% of BC cases and are targeted via ER modulated therapies. Despite this, ER+BC patients can experience recurrence within 20 years and the majority of BC related deaths can be attributed to metastatic ER+BC. These distant metastases are commonly diagnosed as endocrine therapy resistant. Thus, there is an unmet need to identify novel biomarkers for treating ER+ patients with metastases. We have identified a tumor suppressor gene, singleminded 2s (SIM2s), expressed in breast epithelial cells that inhibits epithelial to mesenchymal transition and metastasis, and is downregulated in the progression of breast disease. In ER+BC cell lines, loss of SIM2s results in upregulation of mesenchymal markers and increased PI3K/Akt signaling. Dysregulation of the PI3K/Akt signaling pathway in ER+BC is involved with tumor progression and acquired therapeutic resistance. Our study suggests loss of SIM2s confers resistance in ER+BC through a PI3K subunit switch resulting in upregulation of pro-survival signaling. MCF7 SIM2 knock out cells exhibit increased expression of mesenchymal markers and undergo a phenotypic change compared to wild type cells. Utilizing a migration/invasion assay, MCF7 SIM2 knock out cells exemplify an increase in invasion potential compared to wild type cells. Furthermore, changes in PI3K subunit expression were observed via western blot and real time qPCR analysis. Clonogenic assays revealed an acquired resistance to PI3Kα inhibition, but a susceptibility to PI3Kδ inhibition. This is a significant finding as a current standard of care for patients with ER+ breast cancer recurrence is PI3Kα inhibition. PI3Kδ is an already approved therapeutic target in chronic lymphocytic leukemia, thus PI3Kδ may present a new therapeutically targetable opportunity for ER+BC recurrence. Elucidating the mechanism for acquired therapeutic resistance is an integral avenue for understanding how breast cancer progresses and improving the prognosis of ER+BC patients. Citation Format: Garhett Wyatt, Rachel Steinmetz, Traci Lyons, Weston Porter. LOSS OF SINGLEMINDED 2S RESULTS IN A PI3K SUBUNIT SWITCH WHICH DRIVES THERAPEUTIC RESISTANCE IN ESTROGEN RECEPTOR POSITIVE BREAST CANCER [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-08.

Maternity Care Deserts and Postpartum Outcomes: Bridging the Gap in Maternal Health Care in Florida [ID 2683485

INTRODUCTION: Over 2.2 million women of reproductive age live in areas, referred to as maternity care deserts (MCD), with inadequate access to postpartum care services. Furthermore, deaths occurring during the postpartum period account for over half of all pregnancy related deaths. This analysis serves to provide an overview of the intricate relationship between health care access and postpartum health while exploring the increased risk of delayed detection of postpartum complications and the association to increasing maternal mortality rates. METHODS: Data provided by the Area Health Resource File were used to identify counties in Florida that met the criteria of a designated MCD. Data collected on all pregnancy-related deaths verified by the Florida Department of Health (2020–2021) and geographic codes for MCD were used to identify significant associations. RESULTS: This study collected data from a total of 1,938 pregnancy related deaths. A significant increase in the number of postpartum related deaths was during that time (75%). More than a quarter were in MCD (26%). An association of postpartum related deaths with MCD showed an increase (22%). 1 in 10 women living in MCD reported to not receive a postpartum care visit, these counties were also noted to be more likely to have limited telehealth access (30%). CONCLUSION: Maternity care desert limitations to postpartum care reduce prevention efforts, increase risk for delayed complications to go undetected, and contribute to the maternal mortality rates. Potential solutions include policy revisions to expand telehealth access and efforts to increase the awareness of the importance of postpartum care.