Cancer Control Research Articles

Comparison of the latest cancer statistics, cancer epidemic trends and determinants between China and the United States

Objective: To provide supports for the cancer prevention and control strategies in China by comparing the disease burden, epidemic trends, 5-year relative survival rate and major determinants of common cancers between China and the United States. Methods: A descriptive secondary analysis was conducted using data extracted from the GLOBOCAN database, the Surveillance, Epidemiology, and End Results database, Global Burden of disease 2019 database, and previous studies. The main indicators included the cases of malignant tumors in different sites, the cases of deaths, the age-standardized incidence (world standard incidence) and mortality (world standard mortality), the 5-year relative survival rate, and population attributable fraction (PAF). Results: In 2022, an estimated 4.825 million new cases and 2.574 million deaths of malignant neoplasms in China. The world standard incidence rate (201.6/100 000) in China was lower than that in the United States (367.0/100 000), and the world standard mortality rate (96.5/100 000) was higher than that in the United States (82.3/100 000). Lung cancer ranked first in the disease burden of malignant tumors in China, the new cases and deaths accounted for 22.0% and 28.5% of all malignant tumors, respectively. The top three malignant tumors in China were breast cancer (11.5%), prostate cancer (9.7%) and lung cancer (9.5%), which were also among the top five causes of death. However, the second to fifth leading causes of death from malignant tumors in China were digestive system tumors (liver cancer 12.3%, stomach cancer 10.1%, colorectal cancer 9.3%, and esophageal cancer 7.3%). From 2000 to 2018, the world standard incidence of malignant tumors showed an increasing trend and the world standard mortality of malignant tumors showed a decreasing trend in China, while the world standard incidence and mortality of malignant tumors in the United States showed a significant decreasing trend after 2000. The incidence of breast cancer, colorectal cancer and thyroid cancer increased rapidly in China, while the incidence and mortality of stomach cancer, liver cancer and esophageal cancer decreased, but they still had a heavy disease burden. From 2003 to 2015, the overall 5-year relative survival rate of malignant tumors increased from 30.9% to 40.5% in China. However, with the exception of esophageal cancer, the 5-year relative survival rates of other major malignant tumors were lower than those in the United States. In 2019, the PAF of malignant tumors death attributable to potential modifiable risk factors was 48.3% in China, which was similar to the United States (49.8%). Of these, smoking was the most important attributable risk factor, and the PAF was more than 30% both in China and the United States. In addition, about 18.8% of malignant tumors were caused by preventable chronic infections, such as hepatitis B virus and Helicobacter pylori, while less than 4% of malignant tumors in the United States were caused by infection. Conclusions: China has made great progress in the prevention and treatment of malignant tumors, but it still faces a serious disease burden. The cancer spectrum is changing from developing countries to developed countries. We should pay attention to modifiable factors, take comprehensive measures, and prevent cancer scientifically.

Abstract PR005: Final results from a Phase I trial of intravesical chemoimmunotherapy with gemcitabine and Bacillus Calmette-Guérin (BCG) for patients with BCG-exposed high-grade non-muscle invasive bladder cancer

Abstract Background: Although retreatment with BCG is considered standard of care for patients with BCG-exposed high-grade (HG) non-muscle invasive bladder cancer (NMIBC), less than 50% of patients are expected to respond. As such, the ability to augment the efficacy of BCG in this population remains a critical unmet need. Preclinical studies suggest that intravesical gemcitabine (Gem) may demonstrate synergistic efficacy with BCG by favorably altering the tumor microenvironment. We therefore sought to evaluate the safety, tolerability, and preliminary clinical efficacy of GemBCG in patients with BCG-exposed HG NMIBC through an IRB-approved Phase I/II clinical trial. Methods: Patients with BCG-exposed papillary HG NMIBC (Ta/T1) with or without carcinoma in situ (CIS) that recurred within 24 months of BCG therapy were eligible for this trial. Exclusion criteria included BCG-unresponsive disease, contraindication to BCG therapy, or ureteral/urethral urothelial disease. Consenting patients underwent complete transurethral resection of bladder tumors followed by intravesical Gem twice weekly (weeks 1, 4, 7, 10) for a total of 8 doses. Dose escalation of Gem was performed from 50-2000 mg using a Bayesian modified continual reassessment method. Intravesical Gem instillations alternated with weekly intravesical TICE BCG therapy (weeks 2, 3, 5, 6, 8, 9) for a total of 6 doses fixed at 50 mg followed by maintenance BCG in responders. Complete response (CR) rates and progression to muscle-invasive bladder cancer (MIBC) or cystectomy were evaluated at 12 months of follow up in the Phase I cohort. Results: A total of 25 patients was enrolled (median age 70 years [IQR 64-75]), all of which have at least 12 months of follow up. Of these, 88% (22/25) were male. Median duration of bladder cancer treatment prior to enrollment was 385 days (IQR 173-634), and 28% (7/25) previously received either maintenance therapy (3/25) or >1 induction courses of BCG (4/25). Based on centralized pathology review, a total of 68% had CIS ± papillary disease (8 HGTa, 5 HGT1, and 4 Tis), while 32% had papillary-only disease (4 HGTa and 4 HGT1). No dose limiting toxicities were observed, and 14/25 patients were treated at the maximum tolerated dose. The treatment was well tolerated with no patient experiencing treatment-related Grade 3-5 toxicity. CR rates at 6 months and 12 months were 96% (24/25) and 92% (23/25), respectively. No progression to MIBC or radical cystectomy was observed. Conclusion: Combination GemBCG in BCG-exposed HG NMIBC is well tolerated and appears to provide excellent cancer control. Based on these encouraging findings and the ongoing phase II portion (NCT04179162), a prospective randomized controlled trial comparing GemBCG to BCG alone for BCG-exposed NMIBC is planned through the National Clinical Trial Network (Alliance A032303). Citation Format: Syed M. Alam, Christopher D. Gaffney, Jessica Lavery, Merve Basar, Neeta D'Souza, Christian Hernandez, Melissa McCarter, Patricia Moran, Kristen Stasi, Kara Worth, Daniel Sjoberg, Guido Dalbagni, Timothy Donahue, Sherri Donat, Dean Bajorin, Bernard H. Bochner, Alvin Goh, Judy Sarungbam, Hikmat Al-Ahmadie, Eugene J. Pietzak. Final results from a Phase I trial of intravesical chemoimmunotherapy with gemcitabine and Bacillus Calmette-Guérin (BCG) for patients with BCG-exposed high-grade non-muscle invasive bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr PR005.

Cardiovascular health and cancer risk associated with plant based diets: An umbrella review.

Cardiovascular diseases (CVDs) and cancer are the two main leading causes of death and disability worldwide. Suboptimal diet, poor in vegetables, fruits, legumes and whole grain, and rich in processed and red meat, refined grains, and added sugars, is a primary modifiable risk factor. Based on health, economic and ethical concerns, plant-based diets have progressively widespread worldwide. This umbrella review aims at assessing the impact of animal-free and animal-products-free diets (A/APFDs) on the risk factors associated with the development of cardiometabolic diseases, cancer and their related mortalities. PubMed and Scopus were searched for reviews, systematic reviews, and meta-analyses published from 1st January 2000 to 31st June 2023, written in English and involving human subjects of all ages. Primary studies and reviews/meta-analyses based on interventional trials which used A/APFDs as a therapy for people with metabolic diseases were excluded. The umbrella review approach was applied for data extraction and analysis. The revised AMSTAR-R 11-item tool was applied to assess the quality of reviews/meta-analyses. Overall, vegetarian and vegan diets are significantly associated with better lipid profile, glycemic control, body weight/BMI, inflammation, and lower risk of ischemic heart disease and cancer. Vegetarian diet is also associated with lower mortality from CVDs. On the other hand, no difference in the risk of developing gestational diabetes and hypertension were reported in pregnant women following vegetarian diets. Study quality was average. A key limitation is represented by the high heterogeneity of the study population in terms of sample size, demography, geographical origin, dietary patterns, and other lifestyle confounders. Plant-based diets appear beneficial in reducing cardiometabolic risk factors, as well as CVDs, cancer risk and mortality. However, caution should be paid before broadly suggesting the adoption of A/AFPDs since the strength-of-evidence of study results is significantly limited by the large study heterogeneity alongside the potential risks associated with potentially restrictive regimens.

The aged tumor microenvironment limits T cell control of cancer.

The etiology and effect of age-related immune dysfunction in cancer is not completely understood. Here we show that limited priming of CD8+ T cells in the aged tumor microenvironment (TME) outweighs cell-intrinsic defects in limiting tumor control. Increased tumor growth in aging is associated with reduced CD8+ T cell infiltration and function. Transfer of T cells from young mice does not restore tumor control in aged mice owing to rapid induction of T cell dysfunction. Cell-extrinsic signals in the aged TME drive a tumor-infiltrating age-associated dysfunctional (TTAD) cell state that is functionally, transcriptionally and epigenetically distinct from canonical T cell exhaustion. Altered natural killer cell-dendritic cell-CD8+ T cell cross-talk in aged tumors impairs T cell priming by conventional type 1 dendritic cells and promotes TTAD cell formation. Aged mice are thereby unable to benefit from therapeutic tumor vaccination. Critically, myeloid-targeted therapy to reinvigorate conventional type 1 dendritic cells can improve tumor control and restore CD8+ T cell immunity in aging.

Prognostic impact of chronic lymphocytic leukemia comorbidity index in a young population: a real-world evidence study of a national gulf region cohort

In chronic lymphocytic leukaemia (CLL), comorbidities assessed by the CLL comorbidity index (CLL-CI) have been associated with outcomes in Western cohorts. We conducted a retrospective analysis of an unselected Middle Eastern cohort of newly diagnosed CLL patients seen at the Kuwait Cancer Control Center (n = 300). Compared to Western studies, these Middle Eastern patients were diagnosed at a younger age (median of 59) and had a higher comorbidity burden (69% non-low risk CLL-CI). A higher CLL-CI score was independently associated with significantly shorter event-free survival and greater risk of death. Our analysis demonstrates that CLL-CI is a valuable tool for comorbidity assessment and prognostic influence in (relatively young) Middle Eastern CLL patients.

Projected estimates of cancer in Canada in 2024.

Cancer surveillance data are essential to help understand where gaps exist and progress is being made in cancer control. We sought to summarize the expected impact of cancer in Canada in 2024, with projections of new cancer cases and deaths from cancer by sex and province or territory for all ages combined. We obtained data on new cancer cases (i.e., incidence, 1984-2019) and deaths from cancer (i.e., mortality, 1984-2020) from the Canadian Cancer Registry and Canadian Vital Statistics Death Database, respectively. We projected cancer incidence and mortality counts and rates to 2024 for 23 types of cancer, overall, by sex, and by province or territory. We calculated age-standardized rates using data from the 2011 Canadian standard population. In 2024, the number of new cancer cases and deaths from cancer are expected to reach 247 100 and 88 100, respectively. The age-standardized incidence rate (ASIR) and mortality rate (ASMR) are projected to decrease slightly from previous years for both males and females, with higher rates among males (ASIR 562.2 per 100 000 and ASMR 209.6 per 100 000 among males; ASIR 495.9 per 100 000 and ASMR 152.8 per 100 000 among females). The ASIRs and ASMRs of several common cancers are projected to continue to decrease (i.e., lung, colorectal, and prostate cancer), while those of several others are projected to increase (i.e., liver and intrahepatic bile duct cancer, kidney cancer, melanoma, and non-Hodgkin lymphoma). Although the overall incidence of cancer and associated mortality are declining, new cases and deaths in Canada are expected to increase in 2024, largely because of the growing and aging population. Efforts in prevention, screening, and treatment have reduced the impact of some cancers, but these short-term projections highlight the potential effect of cancer on people and health care systems in Canada.

Survey of awareness and beliefs about cancer (ABC) in Tehran Province, Iran

IntroductionKnowledge, attitudes, and practices are essential measures for planning and evaluating cancer control programs. Little is known about these in Iran.MethodsWe conducted a population-based interview survey of adults aged 30–70 using the Farsi version of the Awareness and Beliefs about Cancer questionnaire in the capital province of Tehran, Iran, 2019. We calculated weighted estimates of levels of cancer knowledge, attitudes, and practices to allow for different selection probabilities and nonresponse. We used multivariate logistic regression to understand demographic factors associated with bowel, cervix, and breast screening practices.ResultsWe interviewed 736 men and 744 women. The mean number of recalled cancer warning signs was less than one; 57.7% could not recall any cancer warning signs. Participants recognized 5.6 out of 11 early cancer warning signs and 8.8 of 13 cancer risk factors. Most (82.7%) did not know that HPV infection was a cancer risk factor. Approximately, half had negative attitudes towards cancer treatment, but over 80% had positive attitudes towards the effectiveness of screening for improving survival. Colorectal, breast, and cervical screening rates were 24%, 42%, and 49%, respectively. Higher socioeconomic status increased the odds of taking up screening for cancer. Women aged 60–70 were less likely to report taking up breast and cervical screening than younger women.DiscussionThe Iranian population has poor awareness and negative attitudes about cancer, and participation in screening programs is low. Public awareness and early detection of cancer should be promoted in Iran.

PH/ Temperature/ Redox and Light-responsive Polymersome Structure and Application in Cancer Therapy: Smart Drug Delivery and Targeted Drug Release.

Improvements in cancer treatment are largely influenced by more people knowing about it and developing new ways to diagnose and treat it. New methods such as nanotheranostics and the use of tiny particles have greatly improved the diagnosis, control and treatment of cancer. They have also helped overcome problems with traditional treatments. Nanotheranostics contribute to personalized medicine by helping doctors choose the right treatment, track how well the treatment works, and plan future treatments. Polymers have many advantages as smart or durable drug formulations among small therapeutic platforms. These small sacks, which can be used for drug delivery and imaging, are not harmful to natural tissues and are becoming more popular. Scientists have found a special group of tiny particles made of polymers that can carry active ingredients. These particles show the potential of creating a useful platform for the diagnosis and treatment of diseases on a very small scale. In the past ten years, people have become more interested in polymersomes. They have been used for various medical purposes, such as controlling blood sugar, treating cancer and fighting bacteria. Polymers are stronger and more stable than liposomes. Biocompatible and biodegradable polymers are very important for faster translation and creation of useful medical formulations. Recent progress in this field includes the creation of intelligent, centralized and responsive containers. In this review, we will examine and provide information about polymersomes. We will discuss their properties and how they can be used as drug delivery systems.

Carbon ion radiotherapy for mesonephric adenocarcinoma of the uterine cervix: a case report

BackgroundMesonephric adenocarcinoma is an extremely rare subtype of uterine cervical cancer that is associated with a poor prognosis and for which a standardized treatment protocol has not been established. Carbon ion radiotherapy (CIRT) is an emerging radiotherapy modality that has been shown to have a favorable anti-tumor effect, even for tumors resistant to conventional photon radiotherapy or chemotherapy. However, there is no report on CIRT outcomes for mesonephric adenocarcinoma of the uterine cervix.Case presentationWe treated a 47-year-old Japanese woman with mesonephric adenocarcinoma of the uterine cervix (T2bN0M0 and stage IIB according to the 7th edition of the Union for International Cancer Control and International Federation of Gynecology and Obstetrics, respectively) with CIRT combined with brachytherapy and concurrent chemotherapy. CIRT consisted of whole pelvic irradiation and boost irradiation to the gross tumor; 36.0 Gy (relative biological effectiveness [RBE]) in 12 fractions and 19.2 Gy (RBE) in 4 fractions, respectively, performed once a day, four times per week. Computed tomography-based image-guided adaptive brachytherapy was performed after completion of CIRT, for which the D90 (i.e., the dose prescribed to 90% of the target volume) for the high-risk clinical target volume was 20.4 Gy in a total of 3 sessions in 2 weeks. A weekly cisplatin (40 mg/m2) dose was administered concomitantly with the radiotherapy for a total of five courses. From 4 months post-CIRT, the patient developed metastasis of the lung, with a total of 10 lung metastases over 70 months; these lesions were treated on each occasion by photon stereotactic body radiotherapy and/or systemic therapy. At 8 years from initial treatment (i.e., 2 years after the last treatment), the patient is alive without any evidence of recurrence and maintains a high quality of life.ConclusionsThis is the first report of CIRT for treatment of mesonephric adenocarcinoma of the uterine cervix. The present case indicates the potential efficacy of CIRT in combination with brachytherapy for treatment of this disease.

Factors influencing presentation delay among cancer patients: a cross-sectional study in Malaysia

BackgroundCancer represents a significant global public health challenge, with escalating incidence rates straining healthcare systems. Malaysia, like many nations, has witnessed a rise in cancer cases, particularly among the younger population. This study aligns with Malaysia’s National Strategic Plan for Cancer Control Programme 2021–2025, emphasizing primary prevention and early detection to address cancer’s impact. Therefore, we aim to describe the timeliness of cancer care for symptom presentation, socio-demographic, patient, as well as organizational-related factors among patients in Malaysia diagnosed with breast, colorectal, nasopharyngeal, and cervical cancer.MethodsThis cross-sectional study enrolled adult cancer patients diagnosed with breast, cervical, colorectal, or nasopharyngeal cancer from 2015 to 2020 in seven public hospitals/oncology centres across Malaysia. Data were collected through patient-administered surveys and medical records. Presentation delay, defined as the duration between symptom onset and the patient's first visit to a healthcare professional exceeding 30 days, was the primary outcome. Statistical analysis included descriptive statistics and chi-square tests.ResultsThe study included 476 cancer patients, with breast cancer (41.6%), colorectal cancer (26.9%), nasopharyngeal cancer (22.1%), and cervical cancer (9.5%). Over half (54.2%) experienced presentation delays with a median interval of 60 days. Higher proportions of presentation delay were observed among nasopharyngeal cancer patients, employed patients with lower socioeconomic statuses, and those without family history of cancer. Most patients self-discovered their first cancer symptoms (80%), while only one-third took immediate action for medical check-ups. Emotional and organizational factors, such as long waiting times during doctor's visits (47%), were potential barriers to seeking cancer care.ConclusionThis study highlights the significant problem of presentation delay among cancer patients in Malaysia. The delay is influenced by various factors encompassing sociodemographic characteristics, health-seeking behaviours, and healthcare system-related issues. A comprehensive approach addressing both individual barriers and institutional obstacles is imperative to mitigate this presentation delay and improve cancer outcomes.

TNM stage in the Nordic Cancer Registries 2004-2016: Registration and availability.

Stage at cancer diagnosis is an important predictor of cancer survival. TNM stage is constructed for anatomic solid cancer diagnoses from tumor size (T), nodal spread (N) and distant metastasis (M) and categorized in groups 0-I, II, II and IV. TNM stage is imperative in cancer diagnosis, management and control, and of high value in cancer surveillance, for example, monitoring of stage distributions. This study yields an overview of TNM availability and trends in stage distribution in the Nordic countries for future use in monitoring and epidemiologic studies. TNM information was acquired from the cancer registries in Denmark, Norway, Sweden, and Iceland during 2004-2016 for 26 cancer sites in the three former countries and four in Iceland. We studied availability, comparability, and distribution of TNM stage in three periods: 2004-2008, 2009-2013, and 2014-2016, applying a previously validated algorithm of 'N0M0 for NXMX'. For cancers of colon, rectum, lung, breast, and kidney, we examined TNM stage-specific 1-year relative survival to evaluate the quality in registration of TNM between countries. Denmark, Sweden, and Iceland exhibited available TNM stage proportions of 75-95% while proportions were lower in Norway. Proportions increased in Sweden over time but decreased in Denmark. One-year relative survival differed substantially more between TNM stages than between countries emphasizing that TNM stage is an important predictor for survival and that stage recording is performed similarly in the Nordic countries. Assessment and registration of TNM stage is an imperative tool in evaluations of trends in cancer survival between the Nordic countries.

Expert recommendation for real-world study on the application of human papillomavirus vaccine in the Yangtze River Delta region

Cervical cancer has become a global public health problem that poses a serious threat to women's health. Human papillomavirus (HPV) vaccination is an important primary preventive measure for cervical cancer. With the accelerated application of the HPV vaccine in China, conducting real-world studies (RWS) on the application of HPV vaccines can guide the rational use of the vaccine, which is of great significance for the strategy and practice of accelerating the elimination of cervical cancer in China. The Yangtze River Delta Cervical Cancer and Female Lower Genital Tract Infection Prevention and Control Alliance and Yangtze River Delta Immunization Integration Working Group organized an expert group to develop the "Expert recommendation for real-world study on the application of HPV vaccine in the Yangtze River Delta region". Based on the current situation of medical informatization and HPV vaccination administration in China, as well as literature and cases from domestic and international studies, this study describes the data chain of HPV vaccination and evaluation, introduces the study design, study direction, database construction, data governance and statistical analysis of RWS, and provides expert recommendation on the problems in carrying out the practice of HPV vaccine RWS, aiming to guide the RWS of HPV vaccine application and promote the generation of real-world evidence (RWE) in China.

Cancer control Co-benefits of the Climate-Related provisions in the American inflation reduction act.

The American Inflation Reduction Act (IRA) of 2022 contains climate-related provisions that may have significant implications for cancer control and prevention. This commentary assesses the potential co-benefits of the IRA for cancer control efforts, specifically policies and programs to reduce carcinogen exposure via air quality monitoring and air pollution reduction. Allocations through the IRA for air quality improvement, paired with its environmental justice provisions, holds promise for advancing cancer prevention by targeting resources to communities most susceptible to environmental hazards. Moreover, climate resilience measures dictated by the IRA are crucial for oncology professionals grappling with the dual challenges of climate change and cancer care. Climate-driven extreme weather events can exacerbate carcinogen exposure and disrupt access to cancer care, underscoring the need for resilient healthcare infrastructure. The IRA's provisions for clean energy incentives and infrastructure upgrades offer oncology care institutions opportunities to mitigate emissions and bolster resilience against climate-related disruptions, ultimately improving cancer outcomes. Climate-related initiatives funded by the IRA present a unique and timely avenue to advance equitable cancer control efforts. This commentary underscores the critical intersection between climate resilience policy and oncology care, highlighting the potential to promote a healthier and more resilient future for all.

Abstract PO4-09-01: Survival of patients harboring a germline ATM pathogenic/likely pathogenic variant and diagnosed with breast cancer: A case-control study

Abstract Introduction: Patients harboring a pathogenic/likely pathogenic variant (PV/LPV) in ATM present an increased lifetime risk of developing breast cancer (BC). The survival outcomes of these patients are not well-known. Methods: Retrospective, multicentric case-control study. Case group included patients with stage I-III breast cancer harboring a PV/LPV in ATM. Control group included patients with stage I-III breast cancer with a negative germline BC multigene panel testing including ATM gene analysis. Clinical outcomes defined as locoregional relapse-free survival (RFS), distant RFS and breast cancer specific survival were compared between cases and controls. Case group was obtained from five hereditary cancer units and control group was obtained from a sporadic clinic-based cohort. Cases and controls were matched 1:2 by stage, molecular subtype by immunohistochemistry, age at BC diagnosis and year of BC diagnosis. Baseline continuous variables were presented as mean and standard deviation and comparison was performed with Student´s t-test. Baseline categorical variables were presented with number and percentage and comparison were performed using chi-square test. Survival analyses were estimated by Kaplan-Meier curves, the comparison of survival was tested by stratified log-rank testing. Cox proportional hazards model was used to estimate the hazard ratio and confidence intervals. Results: We identified 64 patients (p) with an ATM PV/LPV and 120 controls. Median age at diagnosis was 47 years (28-84) and 46 years (25-88), respectively. The main tumoral characteristics in both groups were ductal (87.5% and 83.5%), luminal B-HER2 negative (37.5% and 45.8%) with histological grade II (54.7% and 58.5%) tumors. Majority of tumors in both groups were diagnosed at stage II (53.1% and 54.2%). Differences between groups were observed in first-degree BC family history (39p (61.9%) vs 51p (43.6%); p=0.02); frequency of multicentric/multifocal tumors (15p (25%) vs 13p (11.1%); p=0.018); contralateral breast cancer (16p (25%) vs 8p (6.7%); p=0.0004) and type of surgery (46.8% conservative surgery in cases and 69.2% in controls; p< 0.001). The result of the germline genetic study was not available for all patients before surgery. Baseline characteristics are summarized in Table 1. With a median follow-up of 6.7 years, we observed more locoregional recurrence and distant recurrence in the control group (ipsilateral local or lymphatic recurrence: 0p (0%) vs 15p (12.5%); p=0.078; metachronic contralateral breast cancer: 7p (12.7%) vs 3p (2.6%); p=0.02; distance recurrence 5p (7.8%) vs 24p (20%); p=0.03. No differences between groups were observed in BC-specific survival analysis, with a median BC-specific survival of 6.24y (4.67-12.1) in patients with ATM and 6.68y (6.12-7.94) in the control group (HR: 1.21 (0.88-1.65); p=0.24). Conclusions: Patients with BC harboring a germline ATM PV/LPV had more multifocal and multicentric disease at diagnosis; and more synchronous and metachronous contralateral BC compared to controls, with no differences in BC-specific survival. Further studies in a larger cohort are warranted to analyze sensitivity to systemic therapies. Table 1. Baseline characteristics of cases and control groups. ER (Estrogen Receptor) positive if > or equal to 1%; PR (Progesterone Receptor) positive if > or equal to 1%; HER2 (Human epidermal growth factor receptor-2); ChTh: Chemotherapy; SLNB: Sentinel Lymph Node Biopsy; AL: Axillar lymphadenectomy Citation Format: Mara Cruellas, Ariadna Roqué, Nuria Dueñas, Iris Teruel, Noemí Tuset Der-Abrain, Alejandra Rezqallah, Víctor Navarro, Laia Joval-Ramentol, Maite Torres, Cristina Saura, Joan Brunet, Judith Balmaña. Survival of patients harboring a germline ATM pathogenic/likely pathogenic variant and diagnosed with breast cancer: A case-control 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 PO4-09-01.

Abstract SoA2-01: Cellular senescence: The senescence-associated secretory phenotype (SASP) and immunity

Abstract Cellular senescence is a stress-induced program following aberrant oncogene activation or administration of cancer therapies, including chemotherapeutic agents and CDK4/6 inhibitors commonly used for treating advanced breast cancers, that results in the proliferative arrest of damaged cells and induction of the senescence associated secretory phenotype (SASP). The SASP involves secretion of inflammatory cytokines and chemokines and upregulation of immunomodulatory cell surface molecules on senescent cells that can promote their clearance by the immune system and tumor resolution. However, if left unchecked, the chronic SASP can also lead to immune suppression and further tissue damage that drives tumor dissemination and metastasis. Here we will discuss our efforts to understand how the SASP can promote anti-tumor immunity and immunotherapy activity in some cancer contexts yet in others immune suppression and tumor promotion. Our findings in other solid tumor contexts demonstrate that the tissue microenvironment has a profound impact of the type of SASP program activated and SASP-mediated immune responses produced and suggest further therapeutic interventions to remodel the SASP for immune control of cancer. Moreover, our results in other hormone-driven cancers suggest that CDK inhibitor and chemotherapy regimens produce different SASPs and resulting effects on myeloid cell and lymphocyte phenotypes that could explain their varying effects on anti-tumor immunity and treatment outcomes. Collectively these findings have important implications for breast cancer treatment and pave the path for rationale combination therapies with senescence-inducing agents to achieve immune control in breast and other immunologically “cold” solid tumor malignancies that are generally unresponsive to current immunotherapy regimens. Citation Format: M. Ruscetti. Cellular senescence: The senescence-associated secretory phenotype (SASP) and immunity [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 SoA2-01.

Abstract PO1-09-09: The journey of HR positive, HER2 negative metastatic breast cancer’s patients: heterogeneities and barriers in Brazilian public health system- a national survey

Abstract Background: Breast cancer is the most common neoplasm in Brazilian women, with high percent of patients diagnosed in advanced stages. Metastatic breast cancer (mBC) is a challenge in the country, where 75% of the population is covered by public health system (Sistema Único de Saúde, SUS). We conducted an on-line survey to describe the journey of human epidermal growth factor receptor 2-negative (HER2-), hormone receptor positive (RH+) mBC patients across public scenario in Brazil. Methods: An on-line survey comprised of 39 to 48 (depending on the kind of some questions, which could open another question in case of affirmative answer) objective questions were sent by e-mail to180 oncologists working in public and private health care system. Questions were focused on assessing wait time for first treatment after admission in the hospital in both systems, availability of oncological drugs within SUS according to essential medicines list by World Health Organization, and presence of palliative and multidisciplinary teams in both systems. Continuous variables were measured by median and mean. The level of statistical significance adopted was 5% with Teste p two-sided. Analyses were performed using SAS statistical software (version 25.0). Results: We had 150 respondents working in SUS and private health system, which fulfilled the inclusion criteria to participate in this survey. The other 30 respondents were excluded from the study because they worked exclusively in SUS or exclusively in the private system, and their answers were not analyzed. Median wait time for surgery was 60 days in the SUS (N=150) and 30 days in the private health system (N=150) e (p < 0,0001). Regardless of chemotherapy provided, median waiting time was 30 and 15 days in the SUS (N=150) and the private health system (N=150), respectively (p < 0,0001). Most oncologists in the SUS (N=125, 83.3%) pointed to endocrine therapy as their first-choice treatment in mBC. Concerning endocrine therapy in the SUS, Gonadotropin-Releasing Hormone Agonist (GnRHa) was available, and it was prescribed by 54 (36.0%) and Fulvestrant for 72 (48.0%) of respondents. Considering chemotherapy, weekly paclitaxel alone or combined with platin were available and they were prescribed by 124 (82.6%) and 109 (72.6%) of oncologists respectively. Vinorelbine was available and it was prescribed according to oncologists’ report by 109 (72.6%) and Pegylated liposomal doxorubicin (PLD) by 38 (25.3%) of oncologists. Oncologists answered agree or strongly agree that they had a multidisciplinary care team in SUS 77,3% (N =116) versus 87,3% (N=131) in the private system (p=0.022). Concerning palliative care 66,09% (N= 99) in the SUS versus 82,0% (N=123) in the private system answered that they agreed or strongly agreed that this service was available (p=0.001). Conclusions: The Brazilian government has continuously improved delivery of services and medicines via the public system (SUS), but there are still significant differences within this system and versus the private sector. Unavailability of endocrine therapy agents as GnRHa and Fulvestrant, and some chemotherapy agents as PLD and Vinorelbine for high percentage of patients, raises the existence of disparities within SUS. Also, longer waiting times for treatment in the SUS, lower availability of support teams such multidisciplinary and palliative care, they point out disparities between SUS and private health systems. The lack of a National Cancer Control Program and low health investment by Brazilian government might explain the difference in cancer patients’ access. Citation Format: Heloísa Resende, Igor Soares, Angélica Renó, Ana Cunha, Vinícius Aguiar, Letícia Tureta, Viviane Pereira. The journey of HR positive, HER2 negative metastatic breast cancer’s patients: heterogeneities and barriers in Brazilian public health system- a national survey [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 PO1-09-09.

Abstract PO3-10-09: The allocation of US $2.6 billion in global funding for breast cancer research between 2016 – 2020: are we investing wisely for breast cancer patients?

Abstract Background: Breast cancer is a global health challenge and the highest incident cancer globally, with over 2 million new cases and 685,000 deaths in 2020, making it the highest incident cancer globally. Furthermore, it is the most prevalent cancer, resulting in the loss of more disability-adjusted life years than any other malignancy. Research is thus crucial to improving outcomes and reducing suffering for breast cancer patients worldwide. This study aimed to analyse global patterns of funding for breast cancer research. Methods: We have previously created a comprehensive database of awards for human cancer research in this period using publicly available data on research funding awards. From this database we extracted all awards relating to breast cancer research, and categorised these by cancer type, cross-cutting research theme and phase of research. Findings: We identified 7051 awards with a total investment of $2.6 billion in 2016-2020, representing 11.2% of all global public and philanthropic cancer research funding during this period. Breast cancer research funding fell year on year, from $773.4 million in 2016 to $243.8 million in 2020. The majority of the investment was in pre-clinical research ($1.9 billion, 73.9%), with clinical trials ($276 million, 10.7%) and public health ($269.2 million, 10.5%) receiving roughly equivalent amounts of funding. The USA accounted for 66.9% of all global breast cancer research investment, with China ($110.4 million, 4.3%) and the UK ($96.6 million, 3.8%) the next largest funders. By research theme, cancer biology research received most funding ($926.2 million, 37.5% of investment), with drug treatment the next best funded research area ($600.5 million, 23.4%), and diagnosis, screening and monitoring third ($396 million, 15.4%). Surgery ($65.2 million, 2.5%) and radiotherapy ($35.3 million, 1.4%) accounted for only a small proportion of research investment. There was minimal investment into breast cancer as a global health issue ($8.1 million, 0.3%). Research into metastatic disease received a greater proportion of investment in breast cancer than in the overall cancer portfolio (23.2% in breast cancer, $597.4 million, compared with 11.7% across all cancers). Conclusions: Breast cancer public and philanthropic research funding is largely invested in pre-clinical research in high-income countries, with the main areas of investment being cancer biology research and drug treatment. The direct benefit to patients from such research is likely to be low and only apparent after a substantial time lag (if at all). Despite their pivotal role in the treatment of the majority of breast cancer patients, surgery and radiotherapy research received a tiny proportion of the overall research investment. Furthermore, relatively little investment is directed towards cancer prevention and early detection, despite their acknowledged key role in cancer control globally. Finally, more equitable research funding is required to align with the global burden of breast cancer, with increased funding for low- and middle-income countries, which account for an increasing proportion of this burden. These data should be considered by funders and policymakers in the allocation of finite resources, which must be invested wisely. Citation Format: Stuart McIntosh, Ellen Copson, Ramsey Cutress, Michael Head. The allocation of US $2.6 billion in global funding for breast cancer research between 2016 – 2020: are we investing wisely for breast cancer patients? [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 PO3-10-09.

Prognostic value of a mandibular canal staging system for primary lesions in patients with lower gingival squamous cell carcinoma: a multicenter, retrospective study.

The Union for International Cancer Control and American Joint Committee on Cancer tumor staging system is used globally for treatment planning. As it may be insufficient for tumor staging of lower gingival carcinomas, we proposed the mandibular canal tumor staging system. In this study, we aimed to compare the two systems for such tumor staging and to identify prognostic markers. This multicenter, retrospective study included patients with lower gingival squamous cell carcinoma who underwent radical surgery during 2001-2018. We compared survival rates (Kaplan-Meier estimator) and patient stratification according to the two systems. The proposed system yielded more balanced patient stratification than the existing system. Progression in the tumor grade according to the proposed system was associated with a poorer prognosis. The 5-year overall and disease-specific survival rates for the entire cohort were 74.9% and 81.8%, respectively. Independent factors affecting overall survival were tumor stage according to the proposed system, excision margins, and number of positive nodes, whereas those affecting disease-specific survival were excision margins and number of positive nodes. Subsite-specific tumor classification should be used for patients with oral cancer, and our results suggest that mandibular canal tumor classification may be effective for patients with lower gingival carcinoma.

Abstract PO2-05-10: 'I am Still Alive': An Interpretative Phenomenological Analysis of Older Women Living with Metastatic Breast Cancer

Abstract Background: Metastatic breast cancer (mBC) is cancer that has spread from the primary organ (breast) to other distant organs such as bone, spine, lungs, brain, and liver. It is a treatable but incurable cancer. While the burden of mBC is devastating to all patients, older mBC patients have poorer prognoses, poor access to care and experience social isolation. This current study is aimed to explore the experiences of older women living with mBC and the impact of belonging to a peer support group (PSG) in Nigeria. Method: Using interpretative phenomenological analysis (IPA), eight women living with mBC aged 50 and above participated in the semi-structured interview. Results: Our findings showed that participants encountered psychological, physiological, and social challenges that are interrelated across four central themes: “Tormented by Pain,” “I am the One that is Going to Die,” “I am Not alone,” and “Winning the ‘war’ against mBC.” While the experiences of older women living with mBC were dominated by different levels of pain, death anxiety, stigma, and financial burden; belonging to a PSG brought participants hope, information, self-worth, and courage. Conclusion: This study has shown PSG should be an important component of cancer control. Hence, healthcare leaders should support and fund the establishment of PSG across Nigeria. Whether mBC is curable or not, the last days of older women living with mBC should be filled with dignity, peer support, and the absence of pain. Citation Format: Runcie C.W. Chidebe, Khadijat Banwo-Fatai, Agha A. Agha, Onyedikachi C. Nwakanma-Akanno, Donnette Narine, Takashi Yamashita, Alejandra Platas, Jennifer Kinney, Phyllis Cummins, Fatima Cardoso. 'I am Still Alive': An Interpretative Phenomenological Analysis of Older Women Living with 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 PO2-05-10.

Defining national research priorities for prostate cancer in Zambia: using the Delphi process for comprehensive cancer policy setting in sub-Saharan Africa

ObjectivesLocally led research on cancer is needed in sub-Saharan Africa to set feasible research priorities that inform national policy. The aim of this project was to develop a research agenda...