Prior History Of Cancer Research Articles

Comparing the resource implications of old and new colorectal adenoma surveillance guidelines in Australia.

The latest update to the Australian adenoma surveillance guideline in 2018 introduced a novel risk stratification system with updated surveillance recommendations. The resource implications of adopting this new system are unclear. To quanitfy the resource demands of adopting new over old adenoma surveillance guidelines. We studied data from 2443 patients undergoing colonoscopies, in which a clinically significant lesion was identified in their latest, or previous procedure(s) across five Australian hospitals. We excluded procedures with inflammatory bowel disease, new or prior history of colorectal cancer or resection, inadequate bowel preparation and incomplete procedures. Old and new Australian surveillance intervals were calculated according to the number, size and histological characteristics of lesions identified. We used these data to compare the rate of procedures according to each guideline. Based on the procedures for 766 patients, the new surveillance guidelines significantly increased the number of procedures allocated an interval of 1 year (relative risk (RR): 1.57, P = 0.009) and 10 years (RR: 3.83, P < 0.00001) and reduced those allocated to half a year (RR: 0.08, P = 0.00219), 3 years (RR: 0.51, P < 0.00001) and 5 years (RR: 0.59, P < 0.00001). Overall, this reduced the relative number of surveillance procedures by 21% over 10 years (25.92 vs 32.78 procedures/100 patient-years), which increased to 22% after excluding patients 75 or older at the time of surveillance (19.9 vs 25.65 procedures/100 patient-years). The adoption of the latest Australian adenoma surveillance guidelines can reduce demand for surveillance colonoscopy by more than a fifth (21-22%) over 10 years.

Association of tamoxifen and raloxifene therapy with cognitive performance, odds of mild cognitive impairment, and neuroimaging markers of neurodegeneration

AbstractBackgroundTamoxifen is used as a selective estrogen receptor modifier (SERM) to treat hormone receptor‐positive breast cancer. Raloxifene, another SERM, has been used for the treatment of osteoporosis in post‐menopausal women. The aim of this cross‐sectional study was to examine whether a history of tamoxifen or raloxifene use was associated with cognitive performance, odds of mild cognitive impairment (MCI), or structural neurodegenerative MRI markers.MethodThe study included women with and without a personal history of breast cancer enrolled in the Mayo Clinic Study of Aging (MCSA). A history of breast cancer and use of SERMs before the MCSA enrollment visit was abstracted using the Rochester Epidemiology Project medical‐linkage system. Participants had a diagnosis of MCI (prevalent) at the time of enrollment into the MCSA. Logistic regression was used to examine associations of SERMs with odds of MCI. Linear regression models were used to examine associations of SERMs with cognitive measures z‐scores (Memory, Executive Function, Language, Visuospatial Skills, Global Cognition), hippocampal volume, and Alzheimer’s disease signature cortical thickness.ResultAmong the women aged ≥ 50 at enrollment in the MCSA, 151 had a history of breast cancer, and 2235 had no prior history of any cancer. Of the 151 women with a history of breast cancer, 42 (28%) had taken tamoxifen and 109 (72%) had not at enrollment in the MCSA; 54 had neuroimaging data (tamoxifen = 16; no tamoxifen = 38). Among the women without prior history of cancer at enrollment in the MCSA, 76 (3%) had taken raloxifene and 2159 (97%) had not; 755 had neuroimaging data (raloxifene = 25; no raloxifene = 730). No significant associations between tamoxifen with global or domain‐specific cognition or odds of MCI were observed among women with a history of breast cancer after adjusting for confounders (Table 1). Likewise raloxifene was not significantly associated with global or domain‐specific cognition or odds of MCI in women without a history of cancer after adjusting for confounders (Table 2). We did not find significant associations between SERMs and any neuroimaging outcome (Table 3).ConclusionOur results suggest use of tamoxifen or raloxifene is not significantly associated with cognition in postmenopausal women.

Clinical evaluation of cancer signal origin prediction and diagnostic resolution following multi-cancer early detection testing.

10520 Background: PATHFINDER (NCT04241796) was a prospective, interventional return of results study that enrolled 6,662 participants (pts) from 7 US institutions to assess clinical implementation of a blood-based multi-cancer early detection (MCED) test. Test results for those with a cancer signal detected also included a cancer signal origin prediction designed to help guide diagnostic evaluations. We analyzed whether the diagnostic evaluations in PATHFINDER were appropriately directed by cancer signal origin predictions, assessed the residual risk of cancer after negative initial evaluation, and examined the role of whole-body imaging (WBI, defined as PET/CT or CT chest/abdomen/pelvis) in diagnostic evaluation. Methods: Analysis included pts with a cancer signal detected result from the two different versions of an MCED test evaluated in PATHFINDER. Prespecified criteria blinded to study results were used to define expected diagnostic evaluations by cancer signal origin prediction. These criteria were then used to judge concordance between cancer signal origin predictions and the diagnostic evaluation actually performed. Definitive cancer or no cancer diagnosis (cancer status at end of study [EOS]) was assessed at 12 months after enrollment (EOS). Results: 39 pts had cancer signal detected results by both test versions. Diagnostic evaluations were consistent with cancer signal origin in 30/39 (77%) cases. Diagnostic resolution was achieved in 32/39 (82%) pts after initial evaluation, while 7/39 (18%) required additional workup. 25 of the 32 (78%) pts who achieved diagnostic resolution after initial evaluation had a cancer signal origin-guided workup. Additional evaluation of the 7 pts not achieving initial diagnostic resolution was based on persistent clinical suspicion of cancer due to prior cancer history (n = 1) or abnormal/equivocal findings on initial evaluation (n = 6). Additional workup led to diagnostic resolution in all 7 cases (3 with cancer and 4 with no cancer confirmed at EOS). WBI was ordered in 27 cases, of whom 9 had a prior cancer history, 10 had non-localizing cancer signal origin (hematologic or indeterminate), and 1 had both. WBI was equivocal or had no impact on diagnostic resolution in 8/27 (30%) cases. Conclusions: Most cases resulted in diagnostic resolution after cancer signal origin-directed diagnostic workup. In pts with a cancer history and negative initial evaluations, and those with equivocal initial evaluations, there was still a risk of cancer, suggesting the need for additional evaluation. WBI was used mostly in those with a cancer history or non-localizing cancer signal origins, and had no impact on diagnosis in almost one-third of pts. Clinical trial information: NCT04241796 .

Barriers to breast cancer screening in a developing middle eastern country: A nationwide survey.

e22517 Background: Breast cancer imposes a significant global health burden not only due to being constantly ranked as the leading malignancy in females, but also due to the immense resulting morbidity and mortality. Despite the presence of screening modalities, the uptake is relatively low due to unidentified barriers in many countries and regions. The Identification of these barriers towards screening is of paramount importance to tackle the health burden imposed by breast cancer, especially in countries like Jordan, a developing middle eastern country. Methods: A self-reporting survey consisting of comprehensive questions regarding the participant’s demographics, medical history, knowledge about breast cancer and the screening modalities was distributed to females aged 25 years and above with no prior history of breast cancer who are residing across the different regions of Jordan. The first consecutive 790 participants were enrolled, and data analysis was performed to identify the key barriers. Results: The mean age of the enrolled study population was 41 ± 9 years old with the majority being married (82.8%), have underwent a higher level of education (86.5%), are non-smokers (75.2%), and are medically insured (72.4%). 209 participants (26.5%) had reported a family history of breast cancer, while 83.4% of the participants reported awareness about breast cancer screening modalities with breast self-examination being the most commonly known modality of screening in 39.2% of the participants. Only 22.4% of the participants were aware of the 3 available screening methods. The majority of the participants (57.1%) did not undergo previous screening. When the participants who did not undergo previous breast cancer screening were compared with those who did, the participants without prior screening were more likely to report the lack of knowledge towards screening modalities (27.7% vs 8.0%) (p-value &lt; 0.001), fear of the results (22.6% vs 13.9%) (p-value = 0.002), fear of pain during or after from the test (10.4% vs 5.9%) (p-value = 0.024), and feeling of embarrassment provoked by the screening test (15.7% vs 6.5%) (p-value &lt; 0.001) as key barriers. On the contrary, there was no statistically significant difference between the two groups when assessing financial aspect of screening uptake as a potential barrier (p-value = 0.860). Conclusions: Despite the considerably high percentage of participants being aware of breast cancer screening modalities, an alarmingly low rate of screening uptake was witnessed due to several barriers. The collective identification of lack of knowledge towards screening modalities and the nature of the available tests, in addition to the fear of the results and pain following the test, and feeling of embarrassment undoubtedly mandates the formulation of comprehensive awareness campaigns that effectively tackle these barriers.

Barriers to cervical cancer screening in a developing Middle Eastern country: A nationwide survey.

10545 Background: In addition to being ranked as the 4th leading malignancy worldwide, cervical cancer is associated with considerable morbidity and mortality resulting in significant burden. However, cervical cancer screening is available and has been proven to significantly minimize the associated morbidity and mortality through early detection. The identification of the barriers towards cervical cancer screening in Jordan, a developing middle eastern country, is of outstanding significance towards effective intervention and minimizing the collective health and socioeconomic burden imposed. Methods: The first consecutive 695 females aged 25 years and above with no prior history of cervical cancer and residing in Jordan across the different regions were enrolled via random probability sampling through a self-reporting survey that comprises of extensive questions regarding the participant’s demographics, medical history, awareness about cervical cancer and its screening methods. Single females were not included in the study due to culture unacceptability of performing pap smears on unmarried females. Statistical analysis was performed to identify the key barriers towards cervical cancer screening in Jordan. Results: The mean age of the enrolled participants was 42 ± 9 years with the majority of the participants having a higher level of education (84.5%), are medically insured (72.4%), and are non-smokers (74.7%). The majority of the participants, 77.7%, did not report a family history of cervical cancer. 472 participants (67.9%) were aware of the availability of a screening modality for cervical cancer, with the majority being informed through awareness campaigns (64.7%). Nonetheless, only 30.1% of the participants previously underwent pap smear for screening purposes. When the participants who did not undergo previous cervical cancer screening were compared with those who did, the participants who did not undergo any prior screening were more likely to identify the lack of information and knowledge towards screening (49.0% vs 9.6%) (p-value &lt; 0.001), fear of the results (81.5% vs 7.2%) (p-value = 0.016), lack of belief in screening and its efficacy (2.1% vs 0.0%) (p-value = 0.037) as crucial and leading barriers. Additionally, the presence of a positive family history for cervical cancer was identified as a statistically significant promoter for screening uptake (p-value = 0.004). Nonetheless, there was no statistically significant difference between the two groups when evaluating the financial aspects of screening or embarrassment from the test as potential barriers, p-value = 0.159 and 0.738, respectively. Conclusions: Lack of knowledge towards screening and belief in its efficacy, and fear of the results were identified as driving barriers towards screening. Effective formulation of comprehensive awareness campaigns is pivotal towards successful intervention to the reported barriers.

Vitamin D deficiency as a risk factor for breast cancer development.

10559 Background: Previous studies and meta-analyses have suggested that women with low levels of vitamin D may be at increased risk of breast cancer development and recurrence. The relationship is suspected to be inverse, nonlinear, and predominantly present in postmenopausal women. The purpose of this study was to use the TriNetX platform to determine the magnitude of breast cancer risk increase for women with significant vitamin D deficiency and evaluate the significance of menopause on vitamin D-associated breast cancer risk. Methods: The TriNetX platform was used to generate patient cohorts via International Classification of Disease-10 (ICD-10) codes. All patients were females over 40, had no prior history of breast cancer (C50), and had been diagnosed with menopause (Z78.0). One cohort had less than 20 ng/mL of vitamin D while the other had greater than 30 ng/mL. The cohorts were balanced for age, race, and ethnicity, resulting in 73,659 patients in each arm. They were then evaluated for the future development of breast cancer (C50). Two additional cohorts were created of premenopausal patients aged 40-55 using the same vitamin D parameters and cohort balancing. Results: Postmenopausal women with vitamin D levels below 20 ng/mL had a 45% greater risk of developing breast cancer (risk ratio 1.45, 95% CI (1.38,1.52), p-value &lt;0.0001). (Table) Deficient premenopausal women were also found to be at significantly increased risk although the absolute risk difference was small (relative risk 1.18, 95% CI (1.10,1.27), p-value &lt;0.0001). Conclusions: These results confirm and also quantify the previously-suspected increased breast cancer risk for women who are deficient in vitamin D. The impact of low vitamin D levels on breast cancer risk in premenopausal patients was statistically significant but small in magnitude, while postmenopausal women were found to have approximately 45% higher risk as compared to women who were not deficient. Vitamin D supplementation for all deficient postmenopausal women should be considered. [Table: see text]

Clinical implications of receptor conversions in breast cancer patients who have undergone neoadjuvant chemotherapy.

In this study, we aimed to determine the incidence of receptor conversions after neoadjuvant chemotherapy (NAC) for breast cancer and assess the rate at which receptor conversion leads to changes in adjuvant therapy regimens. We performed a retrospective review of female breast cancer patients treated with NAC at an academic breast center between January 2017 and October 2021. Patients with residual disease on surgical pathology and complete receptor status information for both pre-NAC and post-NAC specimens were included. Incidence of receptor conversions, defined as a change in at least one hormone receptor (HR) or HER2 status compared to preoperative specimens, was tabulated, and adjuvant therapy modalities were reviewed. Factors associated with receptor conversion were analyzed using chi-square tests and a binary logistic regression. Of the 240 patients with residual disease after NAC, 126 (52.5%) had receptor testing repeated. After NAC, 37 specimens (29%) had a receptor conversion. Receptor conversion resulted in the addition or removal of an adjuvant therapy in 8 patients (6%), indicating a number needed to screen of 16. Prior history of cancer, receipt of initial biopsy at an outside site, HR-positive tumors, and a pathologic stage of II or lower were factors associated with receptor conversions. HR and HER2 expression profiles frequently change after NAC and drive adjustments in adjuvant therapy regimens. Repeat testing of HR and HER2 expression should be considered in patients who receive NAC, especially in patients with early stage, HR-positive tumors whose initial biopsies were performed externally.

Validation of an Eastern Armenian breast cancer health belief survey.

With the fourth highest breast cancer mortality rate in the world, breast cancer prevention and early detection is a priority for Armenia. The Ministry of Health recently initiated efforts to expand access to breast cancer screening. However, little is known about the population's understanding and perception of breast cancer screening programs. This cross-sectional telephone-based study sought to develop and validate an Eastern Armenian language version of the Champion's Health Belief Model Scale (CHBMS) for future use. The English-language CHBMS survey was first rigorously translated by two Armenian nationals and evaluated for face validity. Telephone surveys were then administered to randomly-selected women of approximately screening age (35-65 years) with no prior history of breast cancer living in Armenia's capital between 2019-2020 (n = 103). The translated survey's psychometric properties were evaluated, examining (1) content equivalence, (2) test-retest reliability and (3) internal consistency. Content equivalence and test-retest reliability of the Armenian CHBMS were characterized using correlational analysis with Pearson's coefficient ranging from 0.76-0.97 (p<0.001) and 0.72-0.97 (p<0.001), respectively, for all five CHBMS domains. The translated survey's internal consistency was comparable to the original English-language CHBMS with a Cronbach's alpha greater than 0.7 for all five domains (0.75-0.94 (p<0.001). The translated Eastern Armenian version of CHBMS is a valid, internally-consistent, and reliable research tool that is ready for imminent use among screening-age women to investigate breast cancer perceptions and beliefs as the Armenian government seeks to expand screening access.

The influence of different previous cancer histories on the diagnostic efficacy of Lung Imaging Reporting and Data System.

For lung cancer screening in patients with previous malignant tumors, Lung Imaging Reporting and Data System (Lung-RADS) and other lung cancer screening tools are controversial in terms of requirements for the previous cancer history. This study investigated the effect of the length and type of malignancy history on the diagnostic efficacy of Lung Imaging Reporting and Data System (Lung-RADS) 2022 in pulmonary nodules (PNs). Chest computed tomography and clinical data of PNs in patients with a history of cancer who underwent surgical resection in The First Affiliated Hospital of Chongqing Medical University from January 1, 2018, to November 30, 2021, were retrospectively collected and evaluated based on Lung-RADS. All PNs were divided into 2 groups: the prior lung cancer (PLC) and the prior extrapulmonary cancer (PEPC) groups. Each group was divided into the ≥5 years and <5 years groups based on the duration of cancer history. The diagnostic agreement of Lung-RADS was evaluated based on the pathological diagnosis of nodules after operation. The diagnostic agreement rate (AR) of Lung-RADS and the composition ratios of different types between different groups were calculated and compared. A total of 451 patients with 565 PNs were included in this study. These patients were divided into the PLC group (<5 years: 135 cases, 175 PNs; ≥5 years: 9 cases, 12 PNs) and the PEPC group (<5 years: 219 cases, 278 PNs; ≥5 years: 88 cases, 100 PNs). The diagnostic AR of partial solid nodules (93.0%; 95% CI: 88.7-97.2%) and solid nodules (88.1%; 95% CI: 84.1-92.1%) was close (P=0.13), while both were higher than that of the pure ground-glass nodules (24.0%; 95% CI: 17.5-30.4%; all P values <0.001). Within 5 years, the composition ratio of PNs and the diagnostic AR (PLC: 58.9%, 95% CI: 51.5-66.2%; PEPC: 76.6%, 95% CI: 71.6-81.6%) between the PLC and PEPC groups were all different (all P values <0.001), and the others [composition ratio of PNs & the diagnostic AR: PLC (≥5 years) vs. PEPC (≥5 years); PLC (<5 years) vs. PLC (≥5 years); PEPC (<5 years) vs. PEPC (≥5 years)] were similar (all P values >0.05; range: 0.10-0.93). The length of prior cancer history may affect the diagnostic agreement of Lung-RADS, especially for patients with prior lung cancer within 5 years.

Predictive value of prostate calcification for future cancer occurrence: a retrospective long-term follow-up cohort study.

Although prostate calcification is often identified on pelvic CT images, calcification itself is usually not considered clinically significant. A recent histological study proposed an association between prostate calcification and prostate cancer occurrence. Our aim was to determine the predictive value of prostate calcifications for future prostate cancer occurrence. We retrospectively analysed male patients (≥50 years old) without prior prostate cancer history, who underwent unenhanced pelvic CT between April 2010 and March 2011, and followed-up until December 2021. Cox proportional hazards models were used to assess prostate cancer risk with prostate calcification (defined as a high-density area larger than 3 mm with CT attenuation values ≥ 130 HU), controlling for age, body mass index (BMI), hypertension and diabetes mellitus. A total of 636 male patients (mean age, 68 years ± 9 [standard deviation]) were evaluated. At the end of follow-up, prostate cancer had been more frequently diagnosed in patients with prostate calcification than those without prostate calcification (6.5% vs 2.6%). Multivariate analysis revealed that prostate calcification on CT was a significant predictor of future prostate cancer occurrence (hazard ratio [HR], 2.7; 95% CI: 1.20, 5.91; p = 0.016). No statistical differences were observed in any other factors. Prostate calcification may be a significant predictor of future prostate cancer occurrence, and may be used for risk stratification and to guide screening protocols. Presence of prostate calcification on unenhanced CT scan was associated with increased incidence of prostate cancer occurrence on long term follow-up.

Abstract 1509: Longitudinal profiling of high-risk pediatric malignancies using a multiomics approach

Abstract For many pediatric cancer patients, commonly used gene-panel sequencing tests yield few actionable results, partly due to the complex genomic alterations present. We hypothesized that an unbiased approach, combining whole-genome (WGS) and RNA sequencing (RNAseq), could overcome this and lead to a more comprehensive understanding of these diseases. While prior studies have evaluated WGS and RNAseq in pediatric cancers, few focused primarily on metastatic or relapsed disease. We also placed special focus on longitudinal profiling of patients, including with additional deep sequencing, to capture tumor evolution at the primary and metastatic sites, and to quantify the utility of resampling. We assembled a cohort of 191 high-risk pediatric oncology patients, including solid tumors, CNS tumors, and leukemias/lymphomas. We have representation of patients with relapsed/refractory disease (68), metastatic disease at diagnosis (10), rare diagnoses (19), prior cancer history, and estimated overall survival &amp;lt;50%. We characterized 280 samples with WGS (tumor ~60X; germline ~30X) and/or RNAseq (tumor, polyA selected, ≥20 million reads), including multiple samples taken from 85 patients at different time points (diagnosis, resection, relapse, etc.). Variants (SNVs), structural rearrangements (SVs), mutational signatures, and copy-number alterations (CNAs) were identified using WGS. RNAseq was used to profile gene expression outliers, gene fusions, and expression of variants identified by WGS. The integrated results were used to prioritize potentially actionable variants for each patient. For 20 patients (44 samples), we performed targeted deep sequencing of the DNA (~500X) to profile tumor evolution that cannot be captured by WGS. Multiple sampling from the same patient identified drastic spatial and temporal differences in the genomes and transcriptomes of these tumors. Using the Jaccard index as a measure of concordance between samples shows dynamic changes between samples collected at different time points across multiple modalities (range 0-1, 1 is identical); SNVs ranged from 0.01-0.79, SVs 0.01-0.73, major CNAs 0.07-0.99, minor CNAs 0.38-0.99, up expression outliers 0.12-0.56, down expression outliers 0.04-0.54, and fusions 0-1. Potentially biologically significant differences in therapy-induced mutations by platinum agents were also observed, highlighting the impact of therapy on tumor evolution. Clonal architectures were extracted from deep resequencing and show extensive spatial, temporal, and metastatic heterogeneity in these rare and highly aggressive malignancies that is not captured by WGS alone. Identifying clinically relevant evolution remains a challenge in most patients, but our results suggest that resampling of pediatric tumors at relapse or metastasis will be important for the effectiveness of targeted therapies in the future. Citation Format: Henry J. Martell, Avanthi T. Shah, Alex G. Lee, Bogdan Tanasa, Stanley G. Leung, Aviv Spillinger, Heng-Yi Liu, Inge Behroozfard, Phuong Dinh, María V. Pons Ventura, Florette K. Hazard, Arun Rangaswami, Sheri L. Spunt, Norman J. Lacayo, Tabitha Cooney, Jennifer G. Michlitsch, Anurag K. Agrawal, Marcus R. Breese, Alejandro Sweet-Cordero. Longitudinal profiling of high-risk pediatric malignancies using a multiomics approach [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 1509.

Abstract 1899: Breast density comparison of Hispanic versus Non-Hispanic patients undergoing screening mammograms: Influence of age, parity and breast-feeding

Abstract Background: Higher mammographic breast density is associated with a 4 to 6-fold increased risk of breast cancer. Some single institution retrospective studies show higher breast densities in Hispanic patients (Oppong et al. Breast J. 2018). The prevalence of breast density based on Hispanic ethnicity has not been studied in large database studies. Methods: We performed a retrospective review of women &amp;gt; 40 years undergoing screening mammograms from 2016-2022. Patients with prior history of breast cancer were excluded. We reviewed demographic variables such as race, self-reported ethnicity, body mass index (BMI), parity, breastfeeding and menopausal status. Breast density was characterized as predominantly fatty (PF), scattered fibroglandular (SF), heterogeneously dense (HD) and extremely dense (ED). We used Chi-square and Kruskal-Wallace tests to compare breast density across measured variables, and Ordinal Logistic Regression to compare breast density levels between self-declared ethnicity while adjusting for other variables. Results: 15946 patients were studied; 7317 (46%) identified as Hispanic, the rest non-Hispanic (NH). 6131 (83%) of Hispanics identified as white. Mean age on 1st screening mammogram was 57.64 (SD 7.21). Compared to NH, Hispanics had mean earlier age of 1st mammogram (56.8 vs. 58.3 years), higher BMI (30.5 vs. 28.6) and higher parity (2.53 vs. 1.71). There were significant differences in BI-RADS density categories by Hispanic vs. NH (p&amp;lt;0.001), with differences in PF (20.2% vs. 18.5%), SF (41.7% vs. 39.0%), HD (35.8% vs. 37.2%), and ED (2.3% vs. 5.3%). The ordinal logistic regression model suggests that Hispanics have 17% lower odds than NH of 1 category higher density (OR, 95% CI: 0.83, 0.78-0.88). There were also significant ethnicity differences in age at first exam, BMI, parity, and number of children breast-fed (P&amp;lt;0.001). Adjusting for these ethnicity-associated differences explained the observed differences in density between Hispanic and NH individuals (ORadj, 95% CI: 0.98, 0.92-1.04); adjusting only for BMI served to explain the observed differences in density (ORadj, 95% CI: 0.99, 0.94-1.05). Conclusions: Hispanics were observed to have a lower age of first screening mammogram, higher BMI, higher parity, and breast-fed children compared to non-Hispanics. On univariate analysis, Hispanics were noted to have lower breast density compared to non-Hispanics, these differences do not persist on multivariate analysis. This suggests that BMI likely plays a predominant role in driving the ethnicity-related differences in breast density noted here. Further research efforts should focus on the influence of BMI and other individual-level factors on mammographic density, with a view towards understanding their potential roles in describing differential ethnicity-specific breast cancer risk. Citation Format: Sangeetha Prabhakaran, Vernon S. Pankratz, Jennifer L. Saline, Emily J. Reese. Breast density comparison of Hispanic versus Non-Hispanic patients undergoing screening mammograms: Influence of age, parity and breast-feeding [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 1899.

Mismatch repair-deficient glioma with spatially distinct IDH-mutant and IDH-wild type components arising in the setting of Lynch syndrome.

Pathogenic mutations in MLH1, MSH2, PMS2, and MSH6 compromise DNA mismatch repair mechanisms and in the heterozygous state result in Lynch syndrome, which is typified by a predisposition to endometrial, ovarian, colorectal, gastric, breast, hematologic, and soft tissue cancers. Rarely, germline pathogenic aberrations in these genes are associated with the development of primary central nervous system tumors. We present a report of an adult female with no prior cancer history who presented with a multicentric, infiltrative supratentorial glioma involving both the left anterior temporal horn and left precentral gyrus. Surgical treatment and neuropathological/molecular evaluation of these lesions revealed discordant isocitrate dehydrogenase (IDH) status and histologic grade at these spatially distinct disease sites. A frameshift alteration within the MLH1 gene (p.R217fs*12, c.648delT) was identified in both lesions and subsequently identified in germline testing of a blood sample, consistent with Lynch syndrome. Despite distinct histopathologic features and divergent IDH status of the patient's tumors, the molecular findings suggest that both sites of intracranial neoplasia may have developed as a consequence of underlying monoallelic germline mismatch repair deficiency. This case illustrates the importance of characterizing the genetic profile of multicentric gliomas and highlights the oncogenic potential of germline mismatch repair gene pathogenic alterations within central nervous system gliomas.

MP39-09 RADICAL THERAPY FOR LOW-RISK UPPER TRACT UROTHELIAL CARCINOMA (ROBUUST COLLABORATIVE GROUP)

MP39-09 RADICAL THERAPY FOR LOW-RISK UPPER TRACT UROTHELIAL CARCINOMA (ROBUUST COLLABORATIVE GROUP)

MP13-19 PROSTATE HEALTH INDEX IS ASSOCIATED WITH INCIDENTAL PROSTATE CANCER DETECTION AT TIME OF HOLMIUM LASER ENUCLEATION OF THE PROSTATE

You have accessJournal of UrologyCME1 Apr 2023MP13-19 PROSTATE HEALTH INDEX IS ASSOCIATED WITH INCIDENTAL PROSTATE CANCER DETECTION AT TIME OF HOLMIUM LASER ENUCLEATION OF THE PROSTATE Eric Li, Jenny Guo, Nicholas Dean, Mark Assmus, Ruoji Zhou, Ashley Ross, Matthew Lee, and Amy Krambeck Eric LiEric Li More articles by this author , Jenny GuoJenny Guo More articles by this author , Nicholas DeanNicholas Dean More articles by this author , Mark AssmusMark Assmus More articles by this author , Ruoji ZhouRuoji Zhou More articles by this author , Ashley RossAshley Ross More articles by this author , Matthew LeeMatthew Lee More articles by this author , and Amy KrambeckAmy Krambeck More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003233.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Holmium laser enucleation of the prostate (HoLEP) is a size-independent treatment option for BPH. Unfortunately, despite an appropriate work up for elevated PSA, incidental prostate cancer (iPCa) is found in up to 20% of men undergoing HoLEP. HoLEP is not a therapeutic surgical treatment for prostate cancer, so we sought to identify risk factors for iPCa at the time of HoLEP for pre-operative risk stratification. METHODS: We retrospectively queried for men undergoing HoLEP from January 2021-July 2022, and obtained clinicopathologic data. Men with prior history of prostate cancer were excluded (n=55). T test, chi-squared, Fisher’s exact test, and multivariable logistic regression were performed. RESULTS: On univariable regression, PHI >55 was a significant predictor of iPCa (OR 7.27, 95% CI 1.97-27.5, p=0.003), which remained significant on multivariable adjustment for age (OR 6.76, 95% CI 1.81-25.7, p=0.004). On univariable regression, preoperative PSA (p=0.15), % Free PSA (p=0.12), MRI prostate volume (p=0.69), PSA density (p=0.62), prior negative biopsy (p=0.31), and MRI PIRADS were not significantly associated with iPCa. Of the 39 patients who had pre-operative PIRADS 4 or 5 lesions, 36 patients had pre-operative negative biopsy, and only one patient was ultimately found to have iPCa. 66% (68/103) of iPCa was Gleason Grade Group 1 with a median of 1% of tissue positive. CONCLUSIONS: PHI>55 is an independent predictor of iPCa at time of HoLEP. To our knowledge, this is the first report of the association of PHI and iPCa. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e180 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eric Li More articles by this author Jenny Guo More articles by this author Nicholas Dean More articles by this author Mark Assmus More articles by this author Ruoji Zhou More articles by this author Ashley Ross More articles by this author Matthew Lee More articles by this author Amy Krambeck More articles by this author Expand All Advertisement PDF downloadLoading ...

V08-10 ENDOSCOPIC URETHROPLASTY FOR MANAGEMENT OF MALE MEMBRANOUS URETHRAL STRICTURE

You have accessJournal of UrologyCME1 Apr 2023V08-10 ENDOSCOPIC URETHROPLASTY FOR MANAGEMENT OF MALE MEMBRANOUS URETHRAL STRICTURE Garrett Ungerer, Jayson Kemble, and Jonathan Warner Garrett UngererGarrett Ungerer More articles by this author , Jayson KembleJayson Kemble More articles by this author , and Jonathan WarnerJonathan Warner More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003306.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urethral stricture disease remains a challenging urologic problem, often requiring open repair using grafts or tissue flaps. While endoscopic management offers advantages including minimizing additional surgical trauma to the already scarred urethra and pelvic floor, urethral dilation and/or urethrotomy have been shown to have less durable outcomes compared to other urethroplasty techniques (end-to-end, graft, flap, or two-stage urethroplasty). In this video, we demonstrate a minimally invasive endoscopic approach to urethroplasty using buccal grafting for management of male membranous urethral stricture disease. METHODS: The procedure was performed for management of an 8mm flow limiting stricture within the membranous urethra in a male patient with prior history of prostate cancer managed by radiation who subsequently developed an 8mm flow limiting membranous stricture. The patient is prepped in dorsal lithotomy position. Under direct visualization via cystoscopy, the stricture is first balloon dilated. Next, a posterior strip of the superficial mucosa is resected from the bladder neck to just distal to the area of stricture, creating a 1cm wide bed for the graft to lay. After the defect is measured, a buccal mucosa graft is harvested in standard fashion. Two sutures are placed through the distal corners of the graft with the graft still outside the urethra, and the proximal end of the graft is then secured to the bladder neck using the RD 180 endoscopic suturing device. The proximal suture is cinched tight, pulling the graft to the bladder neck, and the distal end of the graft is pulled tight and flat along the defect using the two sutures attached to the distal graft. The graft is anchored to the posterior urethra using endoscopic Secure Straps. Once the graft is secure, a wire is passed into the bladder under direct visualization and a catheter is passed over wire to hold the graft flat during the subsequent 4 weeks. RESULTS: The procedure lasted 2.5 hours without any complications. Estimated blood loss was 50cc. Following the procedure, the patient was discharged home with a catheter in place. Catheter was removed at 4 weeks. At 10 weeks post-op, cystoscopy showed good graft viability, and peak flow was 20 ml/sec compared to 4 ml/sec pre-operatively. At six months, he continues to do well without evidence of recurrent urethral stricture. CONCLUSIONS: Endoscopic urethroplasty using buccal graft appears to offer a safe and effective repair option that could be considered for management of ureteral strictures. Source of Funding: none to report © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e751 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Garrett Ungerer More articles by this author Jayson Kemble More articles by this author Jonathan Warner More articles by this author Expand All Advertisement PDF downloadLoading ...

407 Moving from observational studies to a clinical trial: the impact of obesity and surgical weight loss on breast imaging, tissue, and cancer screening experience: the B-BRITE study

OBJECTIVES/GOALS: Obesity is associated with increased incidence of breast cancer (BC), yet is not included in many lifetime-risk calculators. Obesity may impact breast cancer screening sensitivity. Retrospective studies show that bariatric surgery is associated with a lower risk of BC, but the effects of surgical weight loss on breast tissue are poorly understood. METHODS/STUDY POPULATION: We proposed a mixed-methods before and after study design to investigate the effects of surgical weight loss on breast tissue via pre- and post-weight loss breast tissue biopsies and imaging. In addition, we aimed to better understand barriers to BC screening for patients with obesity by conducting qualitative interviews. With institutional review board approval, we have begun recruiting 14 cisgender women who plan to undergo Roux-en-Y gastric bypass or sleeve gastrectomy. Participants must be at least 40 years old, with no prior history of breast biopsies or breast cancer and will undergo comprehensive breast cancer screening including mammography with quantitative density assessment, breast MRI, as well as breast core biopsies. RESULTS/ANTICIPATED RESULTS: We hypothesize that obesity and its associated metabolic changes lead to altered breast stroma, including increased inflammation, and tissue stiffness, with subsequent risk of carcinogenesis. If true, we expect to find obese women will have measurably increased inflammatory markers in their breast tissue, which are reduced after bariatric surgery. We expect that change in mammographic density may correlate with fibroglandular volume change on MRI; there are little data on change in background parenchymal enhancement in the setting of obesity and weight change and quantifying this will provide preliminary data for future work. Last, we expect that undergoing BC screening will be easier for patients after weight loss due to constraints of imaging equipment and potential bias in the screening process. DISCUSSION/SIGNIFICANCE: Screening for BC is paramount to improving outcomes yet people with obesity are screened less with worse outcomes. Studying the effects of weight loss on the breast may improve interpretation of breast imaging in the setting of obesity and identify markers of risk. Understanding barriers to screening may help us develop strategies to improve screening.

Patient Cost-Sharing and Utilization of Breast Cancer Diagnostic Imaging by Patients Undergoing Subsequent Testing After a Screening Mammogram

Out-of-pocket costs (OOPCs) have been largely eliminated for screening mammography. However, patients still face OOPCs when undergoing subsequent diagnostic tests after the initial screening, which represents a potential barrier to those who require follow-up testing after initial testing. To examine the association between the degree of patient cost-sharing and the use of diagnostic breast cancer imaging after undergoing a screening mammogram. This retrospective cohort study used medical claims from Optum's deidentified Clinformatics Data Mart Database, a commercial claims database derived from a database of administrative health claims for members of large commercial and Medicare Advantage health plans. The large commercially insured cohort included female patients aged 40 years or older with no prior history of breast cancer undergoing a screening mammogram examination. Data were collected from January 1, 2015, to December 31, 2017, and analysis was conducted from January 2021 to September 2022. A k-means clustering machine learning algorithm was used to classify patient insurance plans by dominant cost-sharing mechanism. Plan types were then ranked by OOPCs. A multivariable 2-part hurdle regression model was used to examine the association between patient OOPCs and the number and type of diagnostic breast services undergone by patients observed to undergo subsequent testing. In our sample, 230 845 women (220 023 [95.3%] aged 40 to 64 years; 16 810 [7.3%] Black, 16 398 [7.1%] Hispanic, and 164 702 [71.3%] White) underwent a screening mammogram in 2016. These patients were covered by 22 828 distinct insurance plans associated with 6 025 741 enrollees and 44 911 473 distinct medical claims. Plans dominated by coinsurance were found to have the lowest mean (SD) OOPCs ($945 [$1456]), followed by balanced plans ($1017 [$1386]), plans dominated by copays ($1020 [$1408]), and plans dominated by deductibles ($1186 [$1522]). Women underwent significantly fewer subsequent breast imaging procedures in dominantly copay (24 [95% CI, 11-37] procedures per 1000 women) and dominantly deductible (16 [95% CI, 5-28] procedures per 1000 women) plans compared with coinsurance plans. Patients from all plan types underwent fewer breast magnetic resonance imaging (MRI) scans than patients in the lowest OOPC plan (balanced, 5 [95% CI, 2-12] MRIs per 1000 women; copay, 6 [95% CI, 3-6] MRI per 100 women; deductible, 6 [95% CI, 3-9] MRIs per 1000 women. Despite policies designed to remove financial barriers to access for breast cancer screening, significant financial barriers remain for women at risk of breast cancer.

How Does Dietary Intake Relate to Dispositional Optimism and Health-Related Quality of Life in Germline BRCA1/2 Mutation Carriers?

Background: The Mediterranean diet (MD) is an anti-inflammatory diet linked to improved health-related quality of life (HRQoL). Germline (g)BRCA1/2 mutation carriers have an increased risk of developing breast cancer and are often exposed to severe cancer treatments, thus the improvement of HRQoL is important. Little is known about the associations between dietary intake and HRQoL in this population. Methods: We included 312 gBRCA1/2 mutation carriers from an ongoing prospective randomized controlled lifestyle intervention trial. Baseline data from the EPIC food frequency questionnaire was used to calculate the dietary inflammatory index (DII), and adherence to MD was captured by the 14-item PREDIMED questionnaire. HRQoL was measured by the EORTC QLQ-C30 and LOT-R questionnaires. The presence of metabolic syndrome (MetS) was determined using anthropometric measurements, blood samples and vital parameters. Linear and logistic regression models were performed to assess the possible impact of diet and metabolic syndrome on HRQoL. Results: Women with a prior history of cancer (59.6%) reported lower DIIs than women without it (p = 0.011). A greater adherence to MD was associated with lower DII scores (p < 0.001) and reduced odds for metabolic syndrome (MetS) (p = 0.024). Women with a more optimistic outlook on life reported greater adherence to MD (p < 0.001), whereas a more pessimistic outlook on life increased the odds for MetS (OR = 1.15; p = 0.023). Conclusions: This is the first study in gBRCA1/2 mutation carriers that has linked MD, DII, and MetS to HRQoL. The long-term clinical implications of these findings are yet to be determined.

Comparison of Preoperative DOI Estimation in Oral Tongue Cancer With cN0 Disease.

To understand the accuracy of pre- and intraoperative estimation of tumor depth of invasion (DOI). A retrospective case-control study. Patients who presented at 1 institution with oral tongue squamous cell carcinoma that underwent oncologic resection between 2017 and 2019 were identified. Patients that met the inclusion criteria were included. Patients with nodal, distant, or recurrent disease, prior history of head and neck cancer, or preoperative tumor assessment and/or final histopathology that did not include DOI were excluded. Preoperative DOI estimation and technique and pathology reports were obtained. Our primary outcome was the sensitivity and specificity of DOI estimation modalities including full-thickness biopsy (FTB), manual palpation (MP), punch biopsy (PB), and intraoperative ultrasound (IOUS). Tumor DOI was assessed quantitatively preoperatively in 40 patients by FTB (n = 19, 48%), MP (n = 17, 42%), or PB (n = 4, 10%). Additionally, 19 patients underwent IOUS to assess DOI. The sensitivities of FTB, MP, and IOUS for DOI ≥ 4 mm were 83% (confidence interval [CI]: 44%-97%), 83% (CI: 55%-95%), and 90% (CI: 60%-98%), respectively, and the specificities were 85% (CI: 58%-96%), 60% (CI: 23%-88%), and 78% (CI: 45%-94%). Our study demonstrated that DOI assessment tools measured had similar sensitivity and specificity in stratifying patients with DOI ≥4 mm, with no statistically superior diagnostic test. Our results support the need for additional research into nodal disease prediction and continued refinement of ND decisions with respect to DOI.