tbuckley/cabot-search huggingface dataset:
Uptake of risk-reduction, surveillance, and therapeutic interventions among patients with breast cancer with pathogenic germline variants.
Authors: Allison W. Kurian, Sarah M. Nielsen Young, Emily M. Russell, Flavia Facio, Chad Moretz, Brandie Heald, Rachel Ellsworth, Daniel Pineda-Alvarez, Ed Esplin, W. Michael Korn, Nadine M. Tung
Journal: Journal of Clinical Oncology (2024)

10579 Background: Management of breast cancer (BC) patients with pathogenic germline variants (PGVs) can include risk-reducing bilateral mastectomy (BLM), PARP inhibitors (PARPi), enhanced breast imaging (MRI/tomosynthesis), risk-reducing salpingo-oophorectomy (RRSO) and pancreatic cancer surveillance (endoscopic ultrasound, EUS/MR cholangiopancreatography, MRCP). We assessed intervention uptake in &gt;1,400 PGV-positive BC patients. Methods: Germline genetic testing (GGT) data (Invitae Corp.) and insurance claims data (Komodo Healthcare Map) were assembled for female patients with BC or DCIS diagnosed 2015-23, GGT &lt;120 days from diagnosis, and &gt;1 year of claims post-GGT. Inclusion/exclusion criteria followed prior work (PMID 32027353). Genes analyzed were those conferring high (&gt;50%; BRCA1, BRCA2, CDH1, PALB2, PTEN, STK11, TP53) or moderate (20-50%; ATM, BARD1, CHEK2, NF1, RAD51C, RAD51D) BC risk. Multivariable logistic regression models of intervention use included PGV risk, race/ethnicity, age, family cancer history, local metastasis, type of insurance, geographic region and time from diagnosis to GGT. Chi-square tests were used to compare intervention uptake rates by PGV risk (Table). Results: 1,432 patients had &gt;1 PGV in a high- (51%) or moderate-risk (49%) gene: 68% White, 32% lymph node involvement, 69% BC family history, 28% Medicare/Medicaid, mean (SD) age at testing: 51 (12) and mean (SD) days from diagnosis to GGT: 40 (26). The intervention with the highest uptake was BLM (60% in all PGV carriers). BLM, RRSO, and PARPi were significantly more frequent in high- vs. moderate-risk PGV carriers. In the multivariable model, patients with BLM uptake were younger (odds ratio, OR 0.9, 95% confidence interval, CI 0.9-1), more often had family cancer history reported (OR 2, 95% CI 1-3) and had high-risk PGV (OR 5, 95% CI 3-7). Patients with RRSO uptake had higher odds of pancreatic (OR 2, 95% CI 1-2) or ovarian (OR 2, 95% CI 1-3) cancer family history and high-risk PGV (OR 6, 95% CI 4-8) and lower odds of Medicare (OR 0.4, 95% CI 0.2-0.8). Conclusions: Overall, the uptake of interventions was higher in patients with high- compared to moderate-risk PGV. More research, however, is needed on the shared decision-making process, as uptake of BLM was relatively high in those with moderate-risk PGV, and uptake of surveillance measures was relatively low.[Table: see text]
Association of germline <i>HSD3B1</i> (c.1100) genotype with tumoral and clinical outcomes in breast and endometrial cancers.
Authors: Justin Hwang, Shayan Nazari, Andrew Elliott, Ari M. Vanderwalde, Carol A Lange, Melissa Ann Geller, Charles J. Ryan, Chadi Nabhan, Nima Sharifi, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2024)

10587 Background: A germline single-nucleotide polymorphism in HSD3B1 results in adrenal-permissive (c.1100 C) and adrenal-restrictive (c.1100 A) phenotypes with respect to androgen synthesis. In pre- and post-menopausal patients with breast cancer (n=3548 and 7871) and endometrial cancer (n=1588 and 8439), we annotated samples as adrenal permissive (CC/AC) or restrictive (AA) based on HSD3B1 variant status and then examined tumoral characteristics and clinical outcomes. Methods: We utilized tumors from the Caris Life Sciences Precision Oncology Alliance database and inferred germline HSD3B1 c.1100 genotype using variant allele frequencies (VAFs): c.1100 C VAF of 0% defined the AA genotype, VAF of 40-60% defined the AC genotype, and VAF of 100% defined the CC genotype. We explored associations of each HSD3B1genotypes with other genomic (WES) and transcriptomic (RNA-seq) features, as well as with survival outcomes. To performed consider menopausal status we used the patient’s age at the time of biopsy (&gt;55 indicating post-menopausal). Results: In breast cancer (BC) and endometrial cancer (EC), the permissive HSD3B1genotype had greater mRNA expression of the estrogen receptor ( ESR1) and co-alterations of the TP53 (p&lt;0.0001). In post-menopausal ECs, the permissive genotype was associated with increased alterations in the PI-3-kinase pathway ( PTEN, PIK3CA, PIK3R1, p&lt;0.0001). In pre-menopausal HER2+ BCs, the restrictive genotype was associated with worse survival (HR=1.40, 95% CI = 1.05-1.85, p=0.027) and exhibited increases in hallmark GSEA signatures including epithelial-to-mesenchymal transition. Post-menopausal basal BCs with the permissive genotype had numerically higher PD-L1 protein expression (50% vs 13%) and less PI-3-kinase alterations ( PTEN, PIK3R1, p&lt;0.01). Post-menopausal clear cell ECs with the restrictive genotype exhibited worse survival (HR=1.60, 95% CI=1.07-2.38, p=0.03) and were 3-fold more likely to be TMB-high or MSI-high (p&lt;0.05). Distinctly, post-menopausal endometrioid ECs of the restrictive genotype were less likely to be TMB- or MSI-high (p&lt;0.05). Conclusions: Breast and endometrial cancers can be classified as adrenal-permissive or -restrictive based on HSD3B1 c.1100 genotype. This classification distinguishes clinical outcomes and tumoral features, particularly when stratifying by menopausal status. Importantly, these genotypes are differentially associated with druggable pathways (PI-3-kinase) and markers of immune sensitivity (PD-L1, TMB, MSI). [Table: see text]
Impact of the oral contraceptive pill on the rate of ovarian cancer incidence in different races of women.
Authors: Tosha Hedin, Poorvi Kirit Desai, Faiza Manji
Journal: Journal of Clinical Oncology (2024)

10521 Background: The rate of ovarian cancer incidence has drastically decreased over the years, though it is the fifth most leading cause of cancer death in women. Oral contraceptive pills (OCP) are a major cause for the decline due to decreasing the number of ovulations in a woman’s lifetime. In fact, women who have ever used OCPs have a 30-50% lower risk of ovarian cancer incidence compared to women who have never used OCP. This study compares the use of OCP in different races of women and its effect on the decline in incidence of ovarian cancer. Methods: The average rate of incidence per 100,000 cases per year for ovarian cancer in White, Asian and Black females was obtained from the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program SEER*Stat Database: NPCR and SEER Incidence – U.S. Cancer Statistics 2001–2019 Public Use Research Database. The National Center for Health Statistics, National Survey of Family Growth was used to find ever use of OCP among sexually experienced women ages 15–49 in the United States for 2002 and 2015-2019. Results: White women, in the year 2002 and 2019 had a rate of ever OCP use of 87% and 87.5% respectively. During that same time period, they had the most drastic decrease in ovarian cancer incidence of 43%, compared to Black and Asian female population. In 2002, the incidence rate of ovarian cancer for White women was 14.6 per 100,000. 17 years later, in 2019, it dropped to 10.2 per 100,000. Black women had the second highest ever use of OCP and the second highest rate of change for ovarian cancer incidence. In 2002, 79.1% of Black women had ever used OCPs compared to 73% in 2019. In 17 years, the incidence rate per 100,00 decreased 39% for Black women. Incidence rate per 100,000 in 2002 was 10.4 and incidence rate in 2019 was 7.5 per 100,000. Asian women comparatively had the lowest ever use of OCP and the lowest rate of change for ovarian cancer incidence. Data was not available for 2002, but in 2019, Asian women’s ever use of OCP was 65.6%. Incidence of ovarian cancer for Asian women decreased by 21% between the years 2002 to 2019. Rate per 100,000 was 10.8 in 2002 and decreased to 8.9 per 100,000 in 2019. Conclusions: The oral contraceptive pill was made available in the year 1960. Since then, it has been a large factor as to why ovarian cancer incidence has declined. Healthcare disparities and cultural differences play a part in the rate of OCP use across different races of women. This, in turn, leads to varying levels of ovarian cancer incidence decline with White women having the highest rate, followed by Black, then Asian women. Ovarian cancer has a high mortality due to inadequate screening techniques and late diagnosis which is perpetuated by cultural barriers to receiving care. A decreased risk of ovarian cancer should be considered as a benefit when prescribing OCPs and a protective factor among all studied races.
The effects of oral nutritional supplements on functional outcomes and body composition in patients with solid cancer undergoing systemic chemotherapy: A pilot study.
Authors: sora kang, Jeong Suk Koh, Myungwon Lee, Ik-Chan Song, Hyo Jin Lee, Hwan-Jung Yun, Deog Yeon Jo, Hyewon Ryu
Journal: Journal of Clinical Oncology (2024)

10074 Background: Cancer cachexia is a complex syndrome characterized by significant weight loss and depletion of skeletal muscle mass. Despite its profound impact on the well-being of cancer patients, the effective management of cancer cachexia remains a challenging and underexplored aspect of oncology. This study aims to investigate the potential benefits of oral nutritional supplements (ONS) to cancer patients undergoing chemotherapy. Methods: This is single-arm, prospective pilot study. Patients with cancer cachexia undergoing chemotherapy were included. Patients received ONS twice a day for 8 weeks. The ONS contained 200 kcal, 22.5 gram of carbohydrates, 7.5 gram of fat, and 12.5 gram of protein per 200 mL. Primary endpoints were improvements of lean body mass and physical performance. The secondary endpoints were changes of health-care related quality-of-life (HRQoL), nutritional status, and gut microbiomes profiles. EORTC-QLQ-C30 questionnaire, body composition analysis, 4-meter-walk test, hand grip strength test, and fecal microbiome analysis were conducted at baseline and after 8 weeks. The bacterial 16S rRNA gene (V3 and V4 region) was amplified using PCR and sequenced on the Illumina MiSeq platform. The QIIME 2 pipelines were used to analyze the raw data. Results: From January 2023 to October 2023, total of 10 patients were included. There were no significant differences of the mean daily energy intake (p=0.62) and calf-circumferences (p=0.2) between baseline and after 8 weeks. However, participants exhibited a statistically significant improvement in hand-grip strength (p=0.002) and 4-meter walk test (p=0.021) after 8 weeks. In the body composition analysis using dual-energy X-ray absorptiometry, no differences were observed in body weight (p=0.43), fat mass (p=0.62), fat-free mass (p=0.27), and fat-free mass index (p=0.38). Also, no significant differences were detected in the results of HRQoL survey (p=0.85). In the microbiome analysis, no differences of microbiome composition at phylum and genus levels, α-diversity, and β-diversity were observed between baseline and after 8 weeks. Conclusions: While ONS have shown potential in enhancing physical functions of patients with cancer cachexia undergoing chemotherapy, this did not correlate with the anticipated microbiome changes or improvements in body composition. The absence of expected microbiome alterations, despite enriched protein and dietary fiber, underscores the complexity of cachexia and indicates that its management may extend beyond nutritional supplementation alone. Further research should explore the broader context of cachexia, including nutrition, metabolic processes, and the impact of chemotherapy.
In-utero and newborn factors and thyroid cancer incidence in adult women in the Sister Study cohort.
Authors: Thi Van Trinh Tran, Katie O'Brien, Rebecca Troisi, Dale Sandler, Cari Kitahara
Journal: Journal of Clinical Oncology (2024)

10560 Background: Thyroid cancer ranks as the fifth most common cancer in women globally, with 90% of cases classified as differentiated thyroid cancer (DTC). Currently, thyroid cancer etiology remains largely unknown, with childhood exposure to ionizing radiation and obesity among the few established modifiable risk factors. Considering that DTC is diagnosed at relatively younger ages compared to many other cancers, with higher incidence in females versus males, the current study aimed to investigate in-utero and newborn exposures in relation to adult female DTC incidence. Methods: From the Sister Study, a cohort of sisters of women with breast cancer living in the U.S. (including Puerto Rico), we included 47810 women who were cancer-free at baseline (2003–2009). At baseline, participants provided information on their birth and newborn characteristics, and characteristics of their parents before and during pregnancy. Using Cox proportional hazards regression models, we assessed the association between in-utero and newborn factors and self-reported DTC incidence during follow-up. The models were adjusted for attained age (timescale), race/ethnicity, BMI, smoking status, personal history of benign thyroid disease, educational level, household annual income, and Area Deprivation Index. Results: The median age at baseline of the study population was 55.4 (interquartile range [IQR]: 48.9-62.1). During follow-up (median: 13.1 years, IQR: 11.5-15), 233 women were diagnosed with DTC, with medical records available for 72% of cases. Factors associated with a higher incidence of DTC included gestational hypertension or hypertension-related disorders (15 exposed cases, HR= 1.87, 95%CI 1.10-3.16), and higher birth weight (for every additional kilogram HR=1.13, 95%CI 1.00-1.27). The HR for maternal pre-pregnancy or gestational diabetes was 2.33 (5 exposed cases, 95%CI 0.96-5.67). Conversely, being born at least two weeks before the due date was associated with a lower incidence (6 exposed cases, HR=0.35, 95%CI 0.15-0.79). These associations remained consistent when restricting to advanced-stage and large-sized DTCs. We observed no associations for participants’ birth order, time since last pregnancy of the participants' mother, multiple versus singleton birth, ever having been breastfed, parental smoking during pregnancy or age at delivery, maternal morning sickness, or paternal diabetes. Conclusions: In this study, maternal diabetes, maternal hypertension, and birth weight were associated with higher female DTC incidence while being born at least two weeks before the due date was associated with lower DTC incidence. These findings provide evidence that in-utero and newborn exposures may have a long-term influence on thyroid cancer development.
T cell-mediated rejection and cancer risk in 579,905 organ transplant recipients.
Authors: Hye Sung Kim, Wongi Woo, Hyun Joon Shin, Young-Geun Choi, Ankit Bharat, Young Kwang Chae
Journal: Journal of Clinical Oncology (2024)

10552 Background: Prolonged immunosuppression following organ transplant raises post-transplant malignancy (PTM) risk without affecting chronic rejection graft failure (CRGF) rates. Our study investigated if T cell responses during rejection could protect against cancer, whereas T cell suppression in PTM might prevent rejection. Methods: Data from 1987 to 2023 on adult first-time single-organ transplant recipients were collected from the UNOS-OPTN database, excluding those with a history of malignancy. Time-dependent Cox regression and landmark analyses (at 1, 2, 3, 5, 10, 15, and 20 years) were used to explore the link between rejection-induced graft failure (RGF) and PTM. Results: The study included 579,905 recipients (kidney 386,878, liver 108,390, heart 45,046, lung 37,643, pancreas 1,948), with a mean follow-up of 7.3 years. RGF occurred in 9.5% of recipients (kidney 12.1%, liver 1.8%, heart 3.9%, lung 12.0%, pancreas 10.2%; p&lt;0.001), with 2.1% experiencing acute rejection graft failure (ARGF) and 7.4%, CRGF. PTM occurred in 12.0% of recipients (kidney 9.9%, liver 12.4%. heart 20.9%, lung 22.6%, pancreas 11.3%; p&lt;0.001), including breast (0.5%), digestive (1.2%), genitourinary (1.7%), gynecologic (0.1%), head and neck (0.3%), hematologic (1.4%), musculoskeletal (0.1%), neurologic (0.0%), respiratory (1.1%), and skin/Kaposi sarcoma (6.4%). In recipients with RGF, PTM risk significantly decreased (HR 0.21 [0.19-0.24]; p&lt;0.001), with consistent trends observed across seven time landmarks (HR 0.20-0.07; p&lt;0.001). Both ARGF and CRGF were associated with lower PTM risk (HR 0.23 [0.18-0.29], 0.21 [0.19-0.24]; p&lt;0.001). In organ-specific analyses, kidney transplants showed similar outcomes for RGF, ARGF, and CRGF (HR 0.21-0.22; p&lt;0.001). Lung transplants exhibited significant risk reductions with RGF (HR 0.44 [0.22-0.89]; p=0.02) and CRGF (HR 0.47 [0.24-0.94]; p=0.03), with no significant results in other organs. All findings remained consistent even after excluding re-transplantations and deaths due to rejection. Excluding PTM-related deaths from PTM cases significantly lowered RGF risk (HR 0.69 [0.65-0.73]; p&lt;0.001), a trend that was consistent across all time landmarks (HR 0.51-0.80; p&lt;0.001). This inverse pattern was seen in kidney, liver, heart, and lung transplants (HR 0.90 [0.84-0.95], 0.21 [0.11-0.38], 0.21 [0.14-0.31], 0.18 [0.14-0.23]; p&lt;0.001) but not in pancreas transplants (HR 1.62 [0.69-3.77]; p=0.27). Conclusions: This study shows that rejection lowers cancer risk in kidney and lung transplants and that PTM reduces rejection risk in kidney, liver, heart, and lung transplants. Implementing enhanced cancer screening for those who have not experienced rejection may be considered. Further research is needed to elucidate the underlying T cell biology specific to each type of transplant.
Germline variation and risk of immune-related adverse events (irAEs): A real-world BioVU study.
Authors: Justin M. Balko, Lydia Yao, Siwei Zhang, Catherine Fahey, Alexandra Haugh, Andrea Davis, Eric Mukherjee, Christian Hammer, Elizabeth J Phillips, Cosmin A Bejan, Yaomin Xu, Douglas Buckner Johnson
Journal: Journal of Clinical Oncology (2024)

10582 Background: IrAEs are prevalent in patients treated with immune checkpoint inhibitors (ICI) and mimic classical autoimmune diseases. IrAE risk prediction could improve clinical decision making and patient safety for ICI-treated patients. Classical autoimmune diseases show strong associations with germline polymorphisms and with Human Leukocyte Antigen (HLA) variants, though it is unclear if these same genetic risk factors predispose to irAEs. To identify both tolerant and irAE patients, we mined Vanderbilt University Medical Center (VUMC) BioVU, a biorepository of &gt;300K DNA samples linked to de-identified medical records and evaluated genome-wide and imputed HLA class I and II associations with irAE risk. Methods: We identified 1,472 ICI-treated BioVU subjects: 428 with ≥ 1 irAE, and 1044 with no irAEs ≤ 6 months from last ICI treatment. Genotyping was performed by Illumina MEGA EX array. Records were screened for use of irAE therapies ( e.g. systemic corticosteroids, infliximab, levothyroxine) after ICI treatment, with chart adjudication. Association tests were performed using Firth’s logistic regression adjusting for age, sex, ICI regimen, and 3 principal components to assess 1) HLA Class I and II alleles; 2) HLA evolutionary divergence; and 3) GWAS to evaluate total irAEs, organ-specific irAEs, or other specific irAEs (sample size permitting). Endocrine irAEs were excluded to be presented in a separate focused study. Results: In GWAS analyses, 53 SNPs and 23 SNPs were identified significantly (nominal p ≤ 5e-8) associated with GI and neuro-toxicity, respectively. We did not identify any significant HLA class I or II associations with irAE or organ-grouped irAEs, including most evolutionary divergence association tests. We noted marginal association (FDR=0.12, OR=6.85) of rheumatic irAEs with HLA-DRB1*10:01, an HLA class II allele with RA-specific epitope motif. Patients experiencing lung irAEs were more likely to have a high HLA class I and II evolutionary divergence sum (p = 0.013 and p=0.046, respectively). Assessment of associations with specific irAEs, validation of known associations with irAEs or autoimmune disorders, including polygenic risk scores, are underway. Conclusions: We had several SNP-irAE associations, though appropriate classification schemas to maximize power and detect genetic variation remain challenging. We will soon expand with 1,800 additional ICI-treated patients (n=~3,300 in toto), creating a robust resource for irAE genetic associations. [Table: see text]
The global burden of primary liver cancer and underlying etiologies from 1990 to 2021.
Authors: Jonathan M Kocarnik, Miranda May, Alistair Acheson, Kayleigh Bhangdia, Kelly Compton, Frances Dean, Weijia Fu, Louise Penberthy, Natalie Pritchett, Rixing Xu, Nickhill Bhakta, Lisa Force
Journal: Journal of Clinical Oncology (2024)

10573 Background: Liver cancer is a leading cause of global health burden, and was the seventh leading cause of cancer death in 2021. The most common type of liver cancer in adults is hepatocellular carcinoma, which can be due to alcohol, hepatitis B, hepatitis C, non-alcoholic steatohepatitis (NASH), or other causes. In children the most common type of liver cancer is hepatoblastoma. Comprehensive and comparative estimation of liver cancer burden can inform policy decisions and public health interventions to reduce incidence, morbidity, and mortality. This study provides updated liver cancer estimates from 1990 to 2021, and for the first time includes hepatoblastoma. Methods: Using estimation methods from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) we comprehensively estimated total liver cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability adjusted life-years (DALYs). Etiologic proportions from meta-analyses of literature review data were applied to the total. Liver cancers under age 10 were attributed to hepatoblastoma. YLLs were calculated using life expectancy estimates. Prevalence and YLDs were calculated from expected survival, disease sequelae, and disability weights. DALYs were the sum of YLLs and YLDs. Results are presented with 95% Uncertainty Intervals (95% UI). Results: Globally, there were an estimated 529,000 (95% UI 480,000 – 594,000) liver cancer cases and 484,000 (437,000 – 538,000) deaths in 2021, contributing to 12,900,000 (11,600,000 – 14,400,000) DALYs. Since 1990, these represented increases of 114.3% (87.0 – 145.3%) in cases, 102.5% (76.4 – 132.0%) in deaths, and 70.6% (48.7 – 96.8%) in DALYs. For liver cancer etiologies (excluding hepatoblastoma), 37.4% (32.6 – 42.6%) of deaths were due to hepatitis B, 30.3% (26.3 – 34.8%) hepatitis C, 19.1% (15.8 – 22.8%) alcohol, 8.5% (6.9 – 10.3%) NASH, and 4.3% (3.6 – 5.1%) other causes in 2021. Conclusions: These GBD 2021 estimates provide comprehensive estimates of the substantial health burden of liver cancer, highlighting a continued need for public health efforts targeting prevention, vaccination, treatment, or behavioral change.[Table: see text]