Lower Cancer Rates Research Articles

P1084 Safety of tofacitinib and upadacitinib compared to other advanced therapies in ulcerative colitis: a large real-world comparison

Abstract Background Whether adverse events of special interest[1] related to JAK inhibitors (JAKi) are a concern compared to other drugs used in ulcerative colitis (UC) needs investigation. We aimed to assess and compare the frequency of adverse events of special interest by JAKi within the class, and with other advanced therapies, on a large real-world population of UC patients. Methods This was a non-interventional, retrospective study conducted with data obtained from TriNetX from patients with diagnosis of adult UC, exposed to advanced therapies (range 1-1095 days). The final cohort included 866 patients over 444,424 UC patients available in the database who matched the query criteria. Adverse events (any), herpes zoster, cardiovascular events, thromboembolic events, cancer (any), non-melanoma skin cancer were investigated. We compared each JAKi with TNF, IL-23 antagonists, and vedolizumab, and within the class by survival analyses and log-rank test. Propensity score matching and adjustment for confounders, such as age, sex, first or second line advanced therapy, smoking habit and other known baseline risk factors, was done. Statistical significance was set as a p value < 0.05. Results Only tofacitinib and upadacitinib were included, as data on filgotinib were not available. Tofacitinib was associated with statistically significant lower rates of thromboembolic events than anti-TNFs (HR 0.61, 95% CI 0.38-098, p=0.04), and lower rates of cancer than vedolizumab (HR 0.63, 95% CI 0.41-0.96, p=0.03), but higher rates of herpes zoster than anti-IL23 (p=0.001). Upadacitinib showed lower rates of thromboembolic events (p=0.001), but higher rates of herpes zoster reactivation than IL-23 (p=0.001). Similar safety profile was found between tofacitinib and upadacitinib when they were directly compared. Conclusion Anti-JAK show a similar safety profile than all the other drug classes used in UC. Herpes zoster infection/reactivation remains the only adverse event of note for both JAKi.

Five-year Oncologic Outcomes Following Primary Partial Gland Cryo-ablation Prospective Cohort Study of Men With Intermediate-risk Prostate Cancer

To assess 5-year oncologic outcomes following primary partial gland cryo-ablation (PPGCA) in intermediate risk prostate cancer. Of 476 men undergoing PPGCA enrolled in our prospective oncologic and functional outcomes study, 313 had MRI concordant intermediate risk prostate cancer with no out-of-field Gleason Grade Group (GGG) ≥2, gross extracapsular extension or extreme apical disease on pre-treatment mpMRI. PSA was monitored every 6 months, and mpMRI at 6-12, 24, 42 and 60 months. Protocol biopsy at 6-12 months and 24 months were discontinued after interim analysis showing low rates of clinically-significant prostate cancer (csPCa) defined as any GGG≥2 disease. Freedom-from-failure (FFF) was defined as no prostate cancer specific mortality, metastatic disease, or whole-gland salvage treatment (WGST) RESULTS: csPCa was detected in 33 (10.5%) subjects. 91 had ≥4.5 years of follow-up data with a mean of 8.9, 3.4, and 2.0 surveillance PSA tests, MRIs, and prostate biopsies; none were lost to follow-up. At 5-years, rates of freedom-from-recurrence of in-field, out-of-field and overall csPCa were 86% (95% CI: 78-96), 85% (95% CI: 63-94), and 70% (95% CI: 57-84). The proportion with freedom-from-failure (FFF) at 5 years was 89% (95% CI: 83-95). None died from prostate cancer, 1 (1%) developed metastasis, 15 (16.5%) underwent WGST, and 15 (16.5%) underwent salvage focal therapy (FT). Only 3 of 91 (3.3%) eligible men were noncompliant with 5-year surveillance protocol. Very encouraging intermediate-term oncological outcomes following PPGCA were observed with very high compliance to a rigorous prospective protocol for identifying recurrent csPCa.

Abstract A081: Comprehensive examination of disparities in cancer incidences by race, gender, and age over 65 years in Alabama's Black belt counties, USA

Abstract In the United States, significant disparities persist in cancer incidence, mortality, and treatment outcomes, particularly among Black populations. Despite advances in medical care, disparities continue to challenge efforts to achieve health equity. Understanding and addressing these complex issues are imperative to ensure that all individuals, regardless of race or ethnicity, have equal access to effective cancer prevention, diagnosis, and treatment. Alabama stands out as the leading state among the top ten in terms of densely populated Black Belt counties in the United States. With 67 counties in total, Alabama is home to 24 designated Black Belt counties. Given this concentration, Alabama becomes a key focus for comprehending cancer disparities. The ongoing research seeks to examine the occurrence of various types of cancer among the predominant racial groups in the United States, focusing particularly on the Black Belt counties of Alabama. Data on cancer occurrences, obtained from the database of National Cancer Institute (NIH) and the Centers for Disease Control and Prevention (CDC), offer insights into cancer incidences among various demographic groups, age categories, and specific types of cancer spanning the last five years (2016-2020). Analysis of the data, focusing on patients aged 65 years and older, was performed using GraphPad Prism 5 software. Graphs were created to visually represent and interpret the data regarding incidences per 100,000 populations. We observe significantly elevated incidences of major cancer types such as prostate, colon, lung, stomach, pancreas, and liver among Black males, and similarly heightened rates of uterus, cervix, stomach, pancreas, and kidney cancers among Black females, when compared to white populations. Notably, within Alabama's Black Belt regions, only a small number of counties have reported incidences of cancer regardless of gender and cancer types, except for prostate cancer in males and breast cancer in females. Moreover, in certain Black Belt counties, rates of colon and lung cancer (in both males and females), as well as prostate cancer in males and breast cancer in females, are exceptionally elevated compared to both the statewide average in Alabama and even the national average in the United States. Generally, females tend to have lower rates of cancer across various types compared to males. In conclusion, factors contributing to these disparities include genetic predispositions, socioeconomic status, healthcare accessibility, systemic biases, and cultural influences. Further investigations, including molecular screening studies, are imperative to corroborate these health disparities and foster community-wide cancer awareness and public health initiatives. Citation Format: Faith Onomeh, Anathbandhu Chaudhuri. Comprehensive examination of disparities in cancer incidences by race, gender, and age over 65 years in Alabama's Black belt counties, USA [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A081.

Abstract B045: Colorectal cancer screening education intervention for Chamoru and Filipinos in Guam and Hawai‘i: Recommendations for culturally and age relevant education

Abstract Background. Pacific Islanders and Filipinos have low rates of colorectal cancer (CRC) screening. Filipinos in the US territory of Guam and the state of Hawai‘i comprise one of the largest ethnic racial groups in these locations, and CHamoru (Chamorro) in Guam constitute a majority of the population. The CRC age-adjusted mortality rate in Guam (17.3) is higher than the overall US (14.2) with a high rate among CHamoru (23.2). In Guam 45.6% of persons aged 45 and above have met USPSTF screening standards while in Hawai‘i Filipinos have the lowest CRC screening rates (69.9%) among Asian and Pacific Islander ethnic subgroups. Interventions to increase CRC screening in these populations are limited. This study explores recommendations for culturally relevant components of a CRC screening education intervention for CHamoru and Filipinos in Guam and Hawai‘i aged 40 and above. Methods. Qualitative methods employed focus groups (FG) and key informant interviews (KII) to facilitate storytelling, creating a familiar and safe space for knowledge, cultural beliefs, and screening education recommendations. Respective community councils advised on the study. A common FG and KII semi-structure guide was implemented. Purposive and snowball sampling was utilized. FGs were age and gender specific, e.g., men in their 40s, women aged 50+, etc. Three levels of thematic coding were performed using Dedoose and included input from community councils. Coding teams comprised of 3 coders compared for corroboration and recoding continued until coders reached agreement. Results: Five FGs and 12 KIIs (N=37) were conducted with persons aged 40 and above. Participants were CHamoru (46%), Filipino (59%), female (59%), and male (41%). In Guam CRC prevention preferences varied by age and gender; those in their 40s preferred culturally tailored video and less preference for an online module compared to groups age 50, and men identified the need for more awareness and outreach. Filipinos in Hawai‘i were not aware of CRC and prevention prioritizing economic obligations (job) over seeking health services. The preferred characteristics of culturally tailored CRC prevention education in Guam and Hawai‘i were trusted knowledge sources to deliver information, storytelling as a format, and involving families. Participants in Guam also preferred online sources while Hawai‘i preferred all types of media in Filipino languages. Conclusion. CHamoru and Filipinos in Guam and Hawai‘i are receptive to family as a source of information and support for CRC prevention, and hearing personal stories motivates CRC screening. Findings give insight toward age-and culturally-tailored CRC screening education with site specific preferences. Findings will be used to develop family-focused interventions for CHamoru and Filipinos to improve CRC screening. Citation Format: Tressa P. Diaz, Angela Sy, Jena Funakoshi, Elizabeth Elmore, Santino Camacho, Alisa Peralta, Marc Rollon. Colorectal cancer screening education intervention for Chamoru and Filipinos in Guam and Hawai‘i: Recommendations for culturally and age relevant education [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B045.

Abstract A150: Improving FIT and colonoscopy animated videos for colorectal cancer screening: An application of learner verification and revision

Abstract Latino adults in the U.S. have low rates of colorectal cancer (CRC) screening. Using at-home fecal immunochemical tests (FIT) can improve screening rates. This study builds upon three-minute instructional animated videos originally created by the Colorectal Cancer Prevention Network that our team previously translated into Spanish. In the current study, we employed a user-centered approach, known as learner verification and revision (LV&R), to elicit patients’ input on the videos. These videos will be used as part of a text-based intervention aimed at increasing FIT use among Latino adults aged 45-54. This study was part of a larger trial, Community Partnership for Telehealth Solutions to Counter Misinformation and Achieve Equity (PRIME), which aims to test an intervention that integrates the videos with social-needs navigation to boost CRC screening within Latino communities. LV&R integrates theories of health communication and qualitative research to tailor interventions to the needs of target populations. To solicit feedback on the two videos (one on FIT, one on colonoscopy), we interviewed 24 patients (46% male) from a large urban community clinic in Los Angeles. Patients were age-eligible for CRC screening, had been mailed a FIT, texted a link to the videos, and spoke English or Spanish (54% preferred Spanish). Interviews asked about acceptability, comprehension, actionability, and cultural relevance of the videos among our target audience. Interviews were recorded, transcribed, and summarized using rapid qualitative analysis techniques. Interviews revealed positive perceptions of both videos' accessibility, content, and appeal. Participants appreciated the videos’ straightforward language and clear instructions, which were found to be culturally and linguistically acceptable across English and Spanish-speakers. The videos were viewed as informative and persuasive, motivating participants to consider or complete CRC screening and share videos with others. The videos aided in dispelling misinformation related to screening with FIT and/or colonoscopy, particularly for those who had never screened for CRC. Participants liked the length of the videos along with use of appropriate humor to convey complex steps in the screening process. Participants suggested minor improvements such as adding language related to bowel prep, screening guidelines, communication of results, and reassuring language to help with fears to enhance the videos' effectiveness. Overall, these findings underscore the importance of culturally responsive, informative, and engaging materials in promoting CRC screening awareness and participation. Latino patients reported high acceptability, persuasiveness, helpfulness, and cultural appropriateness of animated videos sent via text to educate patients about FIT and colonoscopy. Suggestions for improvement centered on providing more facts about CRC, emphasizing that both men and women are at risk, adding reassuring language to encourage individuals to overcome any fears, and providing more resources for further information. Citation Format: Jennifer S. Rivelli, Jennifer L. Schneider, Blake W. Locher, Katherine A. Vaughn, Meagan C. Shaw, Gloria D. Coronado, Esmeralda Ruiz, Jamie H. Thompson, Anne Escaron. Improving FIT and colonoscopy animated videos for colorectal cancer screening: An application of learner verification and revision [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A150.

Contrast-enhanced mammography for surveillance in women with a personal history of breast cancer

PurposeWomen with a personal history of breast cancer have an increased risk of subsequent breast malignancy and may benefit from more sensitive surveillance than conventional mammography (MG). We previously reported outcomes for first surveillance episode using contrast-enhanced mammography (CEM), demonstrating higher sensitivity and comparable specificity to MG. We now report CEM performance for subsequent surveillance.MethodsA retrospective study of 1,190 women in an Australian hospital setting undergoing annual surveillance following initial surveillance CEM between June 2016 and December 2022. Outcome measures were recall rate, cancer detection rate, contribution of contrast to recalls, false positive rate, interval cancer rate and characteristics of surveillance detected and interval cancers.Results2,592 incident surveillance episodes were analysed, of which 93% involved contrast-based imaging. Of 116 (4.5%) recall episodes, 40/116 (34%) recalls were malignant (27 invasive; 13 ductal carcinoma in situ), totalling 15.4 cancers per 1000 surveillance episodes. 55/116 (47%) recalls were contrast-directed including 17/40 (43%) true positive recalls. Tumour features were similar for contrast-directed recalls and other diagnoses. 8/9 (89%) of contrast-directed invasive recalls were Grade 2–3, and 5/9 (56%) were triple negative breast cancers. There were two symptomatic interval cancers (0.8 per 1000 surveillance episodes, program sensitivity 96%).ConclusionRoutine use of CEM in surveillance of women with PHBC led to an increase in the detection of clinically significant malignant lesions, with a low interval cancer rate compared to previous published series. Compared to mammographic surveillance, contrast-enhanced mammography increases the sensitivity of surveillance programs for women with PHBC.

Machine learning techniques to identify risk factors of breast cancer among women in Mashhad, Iran.

Low survival rates of breast cancer in developing countries are mainly due to the lack of early detection plans and adequate diagnosis and treatment facilities. This study aimed to apply machine learning techniques to recognize the most important breast cancer risk factors. This case-control study included women aged 17-75 years who were referred to medical centers affiliated with Mashhad University of Medical Science between March 21, 2015, and March 19, 2016. The study had two datasets: one with 516 samples (258 cases and 258 controls) and another with 606 samples (303 cases and 303 controls). Written informed consent has been observed. Decision Tree (DT), Random Forest (RF), Logistic Regression (LR), and Principal Component Analysis (PCA) were applied using R studio software. Regarding the DT and RF, the most important features that impact breast cancer were family cancer, individual history of breast cancer, biopsy sampling, rarely consumption of a dairy, fruit, and vegetable meal, while in PCA and LR these features including family cancer, pregnancy number, pregnancy tendency, abortion, first menstruation, the age of first childbirth and childbirth number. Machine learning algorithms can be used to extract the most important factors in the diagnosis of breast cancer in developing countries such as Iran.

Walking Through Elephant Cancer Resistance: What it can teach us about elephants, genetics and disease defenses

Cancer is a disease that affects the whole animal kingdom, but it does not behave equally in all the species. Elephants are one of the animals that even though have a greater number of cells in their body they present a low cancer rate. This phenomenon is also known as the Peto’s Paradox. Scientists have concluded that elephants have greater immunity to cancer because their genome has extra copies of tumor suppressor genes: TP53 and LIF. Even though elephants have a big immunity to cancer, they still get the disease, for example Asian elephants are more susceptible of getting reproductive tract neoplasia. Exploring this information is essential to understand how cancer behaves and how our own genes could help us fight the disease. This paper is a review of the actual knowledge the scientific community has regarding how cancer works in elephants, with the final goal of exploring the meaning this has into our understanding of genomics and how it could help us to develop a cure for cancer. 

Low mutation rate in epaulette sharks is consistent with a slow rate of evolution in sharks

Sharks occupy diverse ecological niches and play critical roles in marine ecosystems, often acting as apex predators. They are considered a slow-evolving lineage and have been suggested to exhibit exceptionally low cancer rates. These two features could be explained by a low nuclear mutation rate. Here, we provide a direct estimate of the nuclear mutation rate in the epaulette shark (Hemiscyllium ocellatum). We generate a high-quality reference genome, and resequence the whole genomes of parents and nine offspring to detect de novo mutations. Using stringent criteria, we estimate a mutation rate of 7×10−10 per base pair, per generation. This represents one of the lowest directly estimated mutation rates for any vertebrate clade, indicating that this basal vertebrate group is indeed a slowly evolving lineage whose ability to restore genetic diversity following a sustained population bottleneck may be hampered by a low mutation rate.

Wild pedigrees inform mutation rates and historic abundance in baleen whales.

Phylogeny-based estimates suggesting a low germline mutation rate (μ) in baleen whales have influenced research ranging from assessments of whaling impacts to evolutionary cancer biology. We estimated μ directly from pedigrees in four baleen whale species for both the mitochondrial control region and nuclear genome. The results suggest values higher than those obtained through phylogeny-based estimates and similar to pedigree-based values for primates and toothed whales. Applying our estimate of μ reduces previous genetic-based estimates of preexploitation whale abundance by 86% and suggests that μ cannot explain low cancer rates in gigantic mammals. Our study shows that it is feasible to estimate μ directly from pedigrees in natural populations, with wide-ranging implications for ecological and evolutionary research.

#5810 SELECTED CARDIOVASCULAR (CV)/NON-CV EVENT RATES IN NON-DIALYSIS-DEPENDENT PATIENTS TREATED WITH ESAS IN US MEDICARE (2017–2019), BY CKD STAGE

Abstract Background and Aims The safety and efficacy of daprodustat in non-dialysis-dependent chronic kidney disease (CKD) patients have been reported in the ASCEND-ND trial [1]. However, CKD stage may affect both the need for anemia treatment as well as outcomes, including potential safety events for anemia treatment. This study describes cardiovascular (CV) and non-CV event rates by CKD stage among patients treated with erythropoietin-stimulating agents (ESAs) in the US Medicare population. Method Using Medicare data for all fee-for-service enrollees, we conducted a retrospective cohort study of patients who had diagnosis of CKD stages 3, 4, or 5 and a first use of ESA in 2017–2019. CKD stage was identified by ICD-10 codes; ESA use was derived using Healthcare Common Procedure Coding System (HCPCS) codes. The date of first ESA use was the index date and CKD stage was defined as the most recent diagnosis on or before index date. We further required patients to have at least 12 continuous months of Medicare Parts A and B coverage (also used as a washout period to identify new ESA users) prior to, and be aged ≥66 years on, the index date. Patients with a history of kidney transplant or who had cancer during the year prior, and those who had a hospitalization for heart failure (HF), myocardial infarction (MI), or stroke in the 4 weeks before, the index date were excluded. Patients were followed from index date to the earliest date of death, loss of Medicare coverage, kidney transplantation or dialysis, or December 31, 2019. Both CV (all-cause death, HF, MI, stroke, thromboembolic events [TEEs], MACE [death, stroke, MI], and MACE+HF) and non-CV (cancer, gastric erosions, ocular events, seizures, and serious infections) events were ascertained, derived from Medical claims using ICD-10 diagnosis, HCPCS, and Current Procedural Terminology codes in the follow-up period. HF, MI, stroke, and serious infection were defined as inpatient events. First event rates were calculated separately by CKD stage, expressed as number of events per 100 patient-years during the follow-up period. Results This study cohort included 50,206 patients; 22,332 had stage 3, 19,177 stage 4, and 8,697 stage 5 CKD at the index date. Median follow-up time was 11.5 months for patients with CKD stage 3, 8.9 months for patients with stage 4, and 3.7 months for patients with stage 5 CKD. Patients with higher (worse) CKD stages were slightly younger (mean ages for stages 3, 4, and 5 were 79.7, 79.1, and 76.8 years); with increasingly more males (42.9%, 45.1%, and 48.5%), increasingly more individuals of non-Hispanic Black race (14.2%, 15.7%, and 19.6%), with lower income (indicated by Medicare/Medicaid dual enrolment and Medicare Part D low-income subsidy), and lower proportion of comorbidities. Rates were higher for most CV events in patients with higher (worse) CKD stages (Table): death rates were 19.5, 22.1, and 28.1 per 100 patient-years for stages 3, 4, and 5, respectively; MI rates were 2.2, 2.9, and 3.2; HF rates were 12.5, 17.2, and 19.0; MACE rates were 22.0, 25.4, and 31.8; and MACE+HF rates were 31.0, 38.7 and 47.8, respectively. Rates of stroke were similar across CKD stages; but no pattern for TEE. For non-CV events, higher (worse) CKD stage had higher rates of first ocular events (17.2, 23.3, and 27.1) and seizures (2.3, 2.7, and 3.4), but lower rates of cancer (21.8, 14.2, and 10.2) and, within this, hematological malignancies (10.4, 4.11 and 2.3). Conclusion Medicare-covered ESA-treated patients with higher CKD stage had higher rates for most events assessed, while malignancy rates were lower. These findings may provide important context when assessing US event rates in non-dialysis-dependent CKD patients. Further investigation could clarify some of the differences between stages, such as rates of malignancy. Rates were reported as crude (unadjusted) and so should be interpreted with caution. Limiting the analysis to ESA-treated patients may have resulted in different event rates than would be expected to occur in the general CKD population. Funding: GSK (study 217316).

Incidence round screening performance among women with dense breasts undergoing abbreviated breast MRI and digital breast tomosynthesis (ECOG-ACRIN EA1141).

10502 Background: The sensitivity of mammography, including digital breast tomosynthesis (DBT), is limited by breast density. Abbreviated breast MRI (AB-MR) significantly increases breast cancer detection in women with dense breasts. In the prevalence (baseline) screening round of the EA1141 trial, AB-MR offered a 2.45-fold higher cancer detection rate (CDR) than DBT. Here we report the CDR and diagnostic accuracies of AB-MR and DBT during the EA1141 incidence screening round and the overall interval cancer rate. Methods: Informed consent was obtained from all participants. Asymptomatic average risk women aged 40-75 years with mammographically dense breasts scheduled for routine screening with DBT were enrolled. All women underwent DBT and AB-MR at baseline (prevalence) and year 1 (incidence) screens which were interpreted independently by 2 different radiologists blinded to the other modality. Women were contacted 11-13 months after the year 1 screen to assess for a subsequent breast cancer diagnosis. Pathology of biopsy was the reference standard for CDR and positive predictive value of biopsy (PPV3). Interval cancers reported during 11-13 months of follow-up until the next annual screening were included in the reference standard for sensitivity and specificity. A post hoc adjustment was made for multiple testing using the Bonferroni method; p-values are reported for comparisons which met the adjusted significance threshold (0.05/5 = 0.01). Reported 95% confidence intervals were not adjusted for multiplicity. Results: Of 1516 enrolled subjects, 1444 completed the baseline and 1291 also the incidence screen. During the latter, 9 women were diagnosed with breast cancer. DBT detected cancer in 5 women (3 DCIS, 2 invasive) for a CDR of 3.9/1000 (5/1291, CI 1.7, 9.0). AB-MR detected cancer in 6 women (0 DCIS, 6 invasive), 4 of which were not detected on DBT, for a CDR of 4.6/1000 (6/1291, CI 2.1, 10.1). The additional imaging (subject-level) rate for DBT was 7.9% (102/1291, CI 6.6%, 9.5%) vs 3.7% (48/1291, CI 2.8%, 4.9%) for AB-MR (p < 0.001). The PPV3 (lesion-level) for DBT was 29.4% (5/17, CI 13.5%, 52.6%) and 15.0% (6/40, CI 6.9%, 29.6%) for AB-MR. During the 2 years of study screening (baseline and year 1), there was 1 interval cancer (palpable lump 348 days after year 1 screen), for an overall interval cancer rate of 0.37/1000 person-years (1/2677 person-years, CI 0.05, 2.65). Sensitivity and specificity were 50.0% (5/10, CI 23.7%, 76.3%) and 98.5% (1261/1280, CI 97.7%, 99.0%) for DBT vs 60% (6/10, CI 31.3%, 83.2%) and 93.3% (1193/1278, CI 91.8%, 94.6%, p < 0.001) for AB-MR. Conclusions: On the incidence screening round, AB-MR detected additional invasive breast cancers not seen on DBT. In addition, a low overall interval cancer rate was observed with combined screening. Although the need for additional imaging was lower for AB-MR, specificity was higher for DBT. Clinical trial information: NCT02933489 .

Low risk of some common cancers in women with anorexia nervosa: Evidence from a national record-linkage study.

Some studies report that women with anorexia nervosa (AN) have lower risk than others of breast cancer, but increased risk of cancers of other sites. No work has been done to quantify the risk in the English population. Retrospective cohort study using a national linked dataset of Hospital Episode Statistics for 1999-2021. We selected individuals with a hospital admission for AN, and compared their relative risk (RR) of developing site-specific cancers, with that in a reference cohort. We identified 75 cancers in 15,029 women hospitalised with AN. There was a low RR of all cancers combined at 0.75 (95%CI 0.59-0.94), and, notably, low RR for breast cancer 0.43 (0.20-0.81), cancers of secondary and ill-defined sites 0.52 (0.26-0.93). The RR for parotid gland cancer was 4.4 (1.4-10.6) within a year of first recorded diagnosis of AN. In men, we found 12 cancers in 1413 individuals hospitalised with AN, but no increased risks beyond the first year of diagnosis of AN. This is the first report on the association between AN and cancers in the all-England population. The study showed low rates of breast cancer, and of all cancers combined, in women hospitalised with AN. It is possible that some of the metabolic or hormonal changes observed in AN could work as a protective factor for breast cancer. More experimental work is needed to identify and explain these factors. The new finding on the higher risk of salivary gland tumours could inform clinicians caring for patients with AN.

HPV-related oropharyngeal cancer early detection in gay and bisexual men is an "orphan" practice: A qualitative analysis among healthcare providers.

Among US men, oropharyngeal cancer (cancer of the back of the mouth and throat) is the 8th most common cancer. If detected early, human papillomavirus (HPV)-16-associated oropharyngeal cancer has a high 5-year survival rate. Risk factors such as high numbers of oral sex partners, disparities in smoking and drinking, and low rates of HPV vaccination may put gay and bisexual men at even higher risk for oropharyngeal cancer. We recruited 21 healthcare providers in Minneapolis-St. Paul, Minnesota and Houston, Texas to participate in semi-structured interviews. Nurses, physician assistants, dental hygienists, and dentists were asked about their clinical experiences serving gay and bisexual men and opinions on potential interventions for the early detection of oropharyngeal cancer. Providers typically did not tailor health screenings and examinations for gay and bisexual men. Participants lacked confidence in their ability to effectively implement routine screening for oropharyngeal cancer. The extent to which oropharyngeal cancer screening was incorporated into clinical practice varied by specialty, and practices necessary to detect it were scattered across clinical environments. HIV- and LGBTQ-focused healthcare providers were more aware of HPV-associated oropharyngeal cancer in gay and bisexual men, and appeared readier to act and lead on this issue. Further studies should (1) evaluate protocols for oropharyngeal cancer detection; (2) identify and assess the acceptability of screening in the community; and (3) study how to best close gaps in health services for gay and bisexual men which might contribute to low early detection rates of oropharyngeal cancer.

Abstract 45: Elephant p53 protects mice from carcinogen induced death

Abstract Elephants naturally have low rates of cancer, potentially due to evolved genetic changes in tumor suppressor elephant TP53 (EP53) and amplification of 19 TP53 retrogenes. A better understanding of the mechanisms of cancer suppression in elephants by EP53 and its retrogenes could lead to more effective human cancer therapeutics. EP53 induces a strong apoptotic response compared to human TP53, especially when combined with EP53-RETROGENE 9 (EP53-R9). EP53-R9 encodes a truncated p53 protein that induces apoptosis of human cancer cells independent of EP53 through a transcription-independent mechanism. To characterize EP53 and EP53-R9’s role in cancer suppression, transgenic mice were generated to replace mouse TRP53 with EP53. Additionally, a tetracycline inducible EP53-R9 gene was inserted into a safe harbor locus in mice. Carcinogenesis studies with 3-Methylcholanthene injection revealed that EP53 mice survived significantly longer compared to heterozygous or homozygousTRP53 mice (p <0.0001, 0.0102). Experiments to assess the protective role of EP53-R9 alone and combined with EP53 are ongoing. Several mouse embryonic fibroblast (MEF) cell lines were generated from these transgenic mice with 14 distinct genotypes with different combinations of TRP53, EP53, and EP53-R9. p53 target gene expression studies showed that MEFs with EP53 induce higher expression of MDM2 and p21 compared to TRP53-containing MEFs, suggesting that the cancer-protective effect observed in EP53 mice is due, in part, to greater activation of p53 signaling. These results support the need for future work to assess the potential of EP53-based therapeutics for human cancer. Citation Format: Lisa M. Abegglen, Jared S. Fowles, Aidan J. Preston, Aaron Rogers, Niraja Bhachech, Brayden B. Barney, Ryan Kennington, David H. Lum, Gareth Mitchell, Joshua D. Schiffman. Elephant p53 protects mice from carcinogen induced death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 45.

Quality of Life in Patients with Pancreatic Cancer—A Literature Review

Pancreatic cancer is the malignant disease with the highest mortality rate, and it ranks third in the world after lung and colon cancer. Identified factors that increase the risk of developing pancreatic cancer include chronic pancreatitis, radiation therapy to the pancreatic area due to another cancer, diabetes mellitus, obesity, smoking, and age. The objective of this study was to present the current state of knowledge on the quality of life of patients diagnosed with pancreatic cancer, factors that determine QoL, and ways of coping with the disease. The low curability and low survival rates of pancreatic cancer significantly affect the quality of life of patients, often in the form of significant deterioration, especially in terms of mental changes, cognitive functions, and coping with the disease. Cognitive decline with comorbid depression is also typical for patients with this type of cancer. Research has shown that the health-related quality of life of patients with pancreatic cancer is low, so further research is needed to improve the situation in this area.

Comprehensive systematic review and meta-analysis on physical health conditions in lesbian- and bisexual-identified women compared with heterosexual-identified women.

Sexual minority individuals experience discrimination, leading to mental health disparities. Physical health disparities have not been examined to the same extent in systematic reviews so far. To provide a systematic review and, where possible, meta-analyses on the prevalence of physical health conditions in sexual minority women (i.e. lesbian- and bisexual-identified women) compared to heterosexual-identified women. The study design is a systematic review with meta-analyses. A systematic literature search in MEDLINE, EMBASE, CENTRAL, CINAHL, and Web of Science databases was conducted on epidemiologic studies on physical health conditions, classified in the Global Burden of Disease project, published between 2000 and 2021. Meta-analyses pooling odds ratios were calculated. In total, 23,649 abstracts were screened and 44 studies were included in the systematic review. Meta-analyses were run for arthritis, asthma, back pain, cancer, chronic kidney diseases, diabetes, headache disorders, heart attacks, hepatitis, hypertension, and stroke. Most significant differences in prevalence by sexual identity were found for chronic respiratory conditions, especially asthma. Overall, sexual minority women were significantly 1.5-2 times more likely to have asthma than heterosexual women. Furthermore, evidence of higher prevalence in sexual minority compared to heterosexual women was found for back pain, headaches/migraines, hepatitis B/C, periodontitis, urinary tract infections, and acne. In contrast, bisexual women had lower cancer rates. Overall, sexual minority women had lower odds of heart attacks, diabetes, and hypertension than heterosexual women (in terms of diabetes and hypertension possibly due to non-consideration of pregnancy-related conditions). We found evidence for physical health disparities by sexual identity. Since some of these findings rely on few comparisons only, this review emphasizes the need for routinely including sexual identity assessment in health research and clinical practice. Providing a more detailed picture of the prevalence of physical health conditions in sexual minority women may ultimately contribute to reducing health disparities.

Abstract C122: Demographic and lifestyle characteristics of cancer survivors in the NIH-All of Us Research Program

Abstract Background: Cancer is the second leading cause of morbidity and mortality in the United States (U.S.), and minoritized ethnic and racial groups are disproportionately affected. Non-Hispanic Black (NHB) adults have the highest death rate among racial and ethnic groups in the U.S. for most cancers, with 73,680 cancer deaths projected in 2022. For U.S. Hispanic/Latino adults, cancer is the leading cause of death, accounting for 20% of deaths. Compared to Non-Hispanic White (NHW) adults, Non-Hispanic Asian (NHA) adults have lower cancer rates; however, cancer-specific disparities in morbidity and mortality exist. The National Institutes of Health All of Us Research Program has one of the largest and most nationally representative samples of adults in terms of socioeconomic status, race and ethnicity, age, and geography. Our study aims to describe the prevalence of cancer among the racially and ethnically diverse cohort of adults enrolled in All of Us. Methods: The All of Us tier five data release includes data from a convenience sample of 323,351 adults recruited and enrolled between May 6, 2018, and April 1, 2021, across 340 sites in the U.S. Using self-reported questionnaire data at the time of study enrollment, we identified 22,676 cancer survivors and described cancer site/types and associated cancer lifestyle characteristics (i.e., demographics, co-morbidities, lifestyle behaviors) by race and ethnicity. Descriptive statistics were calculated using Student’s T and Chi-squared tests for continuous and categorical variables, respectively. Results: Among 323,351 All of Us participants, 7.0% (n = 22,676) self-reported a history of cancer at enrollment. Overall, 88.6% of cancer survivors self-identified as NHW, 3.5% as NHB, 3.4% as Hispanic/Latino, 1.0% as NHA, and 3.6% as other race or ethnicity. Among all survivors, the mean ± standard deviation age was 69 ± 10 years, 56.3% were female, 55.3% had a college education or higher, 31.0% had a household income of $75,000-$150,000, 98.0% were insured, 66.9% were unemployed, 67.0% were partnered, and 93.1% were born in the U.S. The most prevalent cancer was skin cancer (34.5%), followed by cancers of the breast (16.8%) and prostate (10.1%). Breast cancer was the most prevalent cancer among NHA (36.1%), NHB (27.1%), and Hispanics/Latinos (20.1%). Skin cancer was the most common cancer among NHW (37.2%). Among all survivors, 38.8% had hypertension, 39.0 % had high cholesterol, 1.0% had type 1 diabetes, 10.8% had type 2 diabetes, 10.0% had obesity, 38.6% were never smokers, and 70.5% had a family history of cancer. All sociodemographic and lifestyle factors differed statistically (p < 0.05) by race and ethnicity. Conclusion: Approximately seven percent of All of Us adults were cancer survivors, a number that exceeds rates previously reported by diverse, prospective cohorts. Cancer prevalence, as well as lifestyle characteristics, varied across racial and ethnic groups, with breast cancer being the most reported cancer for minoritized groups compared to skin cancer for NHW participants. Citation Format: Tania Y. Peña-Ortiz, Umesh Narayan, Ana Velazquez Mañana, Linda Salgin, Catherine M. Pichardo, Sheila F. Castañeda, Humberto Parada Jr., Linda C. Gallo, Gregory A. Talavera, Margaret S. Pichardo. Demographic and lifestyle characteristics of cancer survivors in the NIH-All of Us Research Program [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C122.

Conditional gene regulation models demonstrate a pro-proliferative role for growth hormone receptor in prostate cancer.

Humans with inactivating mutations in growth hormone receptor (GHR) have lower rates of cancer, including prostate cancer. Similarly, mice with inactivating Ghr mutations are protected from prostatic intraepithelial neoplasia in the C3(1)/TAg prostate cancer model. However, gaps in clinical relevance in those models persist. The current study addresses these gaps and the ongoing role of Ghr in prostate cancer using loss-of-function and gain-of-function models. Conditional Ghr inactivation was achieved in the C3(1)/TAg model by employing a tamoxifen-inducible Cre and a prostate-specific Cre. In parallel, a transgenic GH antagonist was also used. Pathology, proliferation, and gene expression of 6-month old mouse prostates were assessed. Analysis of The Cancer Genome Atlas data was conducted to identify GHR overexpression in a subset of human prostate cancers. Ghr overexpression was modeled in PTEN-P2 and TRAMP-C2 mouse prostate cancer cells using stable transfectants. The growth, proliferation, and gene expression effects of Ghr overexpression was assessed in vitro and in vivo. Loss-of-function for Ghr globally or in prostatic epithelial cells reduced proliferation and stratification of the prostatic epithelium in the C3(1)/TAg model. Genes and gene sets involved in the immune system and tumorigenesis, for example, were dysregulated upon global Ghr disruption. Analysis of The Cancer Genome Atlas revealed higher GHR expression in human prostate cancers with ERG-fusion genes or ETV1-fusion genes. Modeling the GHR overexpression observed in these human prostate cancers by overexpressing Ghr in mouse prostate cancer cells with mutant Pten or T-antigen driver genes increased proliferation of prostate cancer cells in vitro and in vivo. Ghr overexpression regulated the expression of multiple genes oppositely to Ghr loss-of-function models. Loss-of-function and gain-of-function Ghr models, including prostatic epithelial cell specific alterations in Ghr, altered proliferation, and gene expression. These data suggest that changes in GHR activity in human prostatic epithelial cells play a role in proliferation and gene regulation in prostate cancer, suggesting the potential for disrupting GH signaling, for example by the FDA approved GH antagonist pegvisomant, may be beneficial in treating prostate cancer.

Beyond the Lab: What We Can Learn about Cancer from Wild and Domestic Animals.

Cancer research has benefited immensely from the use of animal models. Several genetic tools accessible in rodent models have provided valuable insight into cellular and molecular mechanisms linked to cancer development or metastasis and various lines are available. However, at the same time, it is important to accompany these findings with those from alternative or non-model animals to offer new perspectives into the understanding of tumor development, prevention, and treatment. In this review, we first discuss animals characterized by little or no tumor development. Cancer incidence in small animals, such as the naked mole rat, blind mole rat and bats have been reported as almost negligible and tumor development may be inhibited by increased defense and repair mechanisms, altered cell cycle signaling and reduced rates of cell migration to avoid tumor microenvironments. On the other end of the size spectrum, large animals such as elephants and whales also appear to have low overall cancer rates, possibly due to gene replicates that are involved in apoptosis and therefore can inhibit uncontrolled cell cycle progression. While it is important to determine the mechanisms that lead to cancer protection in these animals, we can also take advantage of other animals that are highly susceptible to cancer, especially those which develop tumors similar to humans, such as carnivores or poultry. The use of such animals does not require the transplantation of malignant cancer cells or use of oncogenic substances as they spontaneously develop tumors of similar presentation and pathophysiology to those found in humans. For example, some tumor suppressor genes are highly conserved between humans and domestic species, and various tumors develop in similar ways or because of a common environment. These animals are therefore of great interest for broadening perspectives and techniques and for gathering information on the tumor mechanisms of certain types of cancer. Here we present a detailed review of alternative and/or non-model vertebrates, that can be used at different levels of cancer research to open new perspectives and fields of action.