Pathway-based signatures predict patient outcome, chemotherapy benefit and synthetic lethal dependencies in invasive lobular breast cancer.

BACKGROUND: Invasive Lobular Carcinoma (ILC) is a morphologically distinct breast cancer subtype that represents up to 15% of all breast cancers. Compared to Invasive Breast Carcinoma of No Special Type (IBC-NST), ILCs exhibit poorer long-term outcome and a unique pattern of metastasis. Despite these differences, the systematic discovery of robust prognostic biomarkers and therapeutically actionable molecular pathways in ILC remains limited. METHODS: Pathway-centric multivariable models using statistical machine learning were developed and tested in seven retrospective clinico-genomic cohorts (n = 996). Further external validation was performed using a new RNA-Seq clinical cohort of aggressive ILCs (n = 48). RESULTS AND CONCLUSIONS: mRNA dysregulation scores of 25 pathways were strongly prognostic in ILC (FDR-adjusted P < 0.05). Of these, three pathways including Cell-cell communication, Innate immune system and Smooth muscle contraction were also independent predictors of chemotherapy response. To aggregate these findings, a multivariable machine learning predictor called PSILC was developed and successfully validated for predicting overall and metastasis-free survival in ILC. Integration of PSILC with CRISPR-Cas9 screening data from breast cancer cell lines revealed 16 candidate therapeutic targets that were synthetic lethal with high-risk ILCs. This study provides interpretable prognostic and predictive biomarkers of ILC which could serve as the starting points for targeted drug discovery for this disease.

Guideline-concordant breast cancer care by patient race and ethnicity accounting for individual-, facility- and area-level characteristics: a SEER-Medicare study.

PURPOSE: To examine racial-ethnic variation in adherence to established quality metrics (NCCN guidelines and ASCO quality metrics) for breast cancer, accounting for individual-, facility-, and area-level factors. METHODS: Data from women diagnosed with invasive breast cancer at 66+ years of age from 2000 to 2017 were examined using SEER-Medicare. Associations between race and ethnicity and guideline-concordant diagnostics, locoregional treatment, systemic therapy, documented stage, and oncologist encounters were estimated using multilevel logistic regression models to account for clustering within facilities or counties. RESULTS: Black and American Indian/Alaska Native (AIAN) women had consistently lower odds of guideline-recommended care than non-Hispanic White (NHW) women (Diagnostic workup: ORBlack 0.83 (0.79-0.88), ORAIAN 0.66 (0.54-0.81); known stage: ORBlack 0.87 (0.80-0.94), ORAIAN 0.63 (0.47-0.85); seeing an oncologist: ORBlack 0.75 (0.71-0.79), ORAIAN 0.60 (0.47-0.72); locoregional treatment: ORBlack 0.80 (0.76-0.84), ORAIAN 0.84 (0.68-1.02); systemic therapies: ORBlack 0.90 (0.83-0.98), ORAIAN 0.66 (0.48-0.91)). Commission on Cancer accreditation and facility volume were significantly associated with higher odds of guideline-concordant diagnostics, stage, oncologist visits, and systemic therapy. Black residential segregation was associated with significantly lower odds of guideline-concordant locoregional treatment and systemic therapy. Rurality and area SES were associated with significantly lower odds of guideline-concordant diagnostics and oncologist visits. CONCLUSIONS: This is the first study to examine guideline-concordance across the continuum of breast cancer care from diagnosis to treatment initiation. Disparities were present from the diagnostic phase and persisted throughout the clinical course. Facility and area characteristics may facilitate or pose barriers to guideline-adherent treatment and warrant future investigation as mediators of racial-ethnic disparities in breast cancer care.

LGBTQ+ cancer: priority or lip service? A qualitative content analysis of LGBTQ+ considerations in U.S. state, jurisdiction, and tribal comprehensive cancer control plans.

The National Comprehensive Cancer Control Program, a Centers for Disease Control and Prevention funded program, supports cancer coalitions across the United States (US) in efforts to prevent and control cancer including development of comprehensive cancer control (CCC) plans. CCC plans often focus health equity within their priorities, but it is unclear to what extent lesbian, gay, bisexual, transgender, queer/questioning, plus (LGBTQ+) populations are considered in CCC plans. We qualitatively examined to what extent LGBTQ+ populations were referenced in 64 U.S. state, jurisdiction, tribes, and tribal organization CCC plans. A total of 55% of CCC plans mentioned LGBTQ+ populations, however, only one in three CCC plans mentioned any kind of LGBTQ+ inequity or LGBTQ+ specific recommendations. Even fewer plans included mention of LGBTQ+ specific resources, organizations, or citations. At the same time almost three fourths of plans conflated sex and gender throughout their CCC plans. The findings of this study highlight the lack of prioritization of LGBTQ+ populations in CCC plans broadly while highlighting exemplar plans that can serve as a roadmap to more inclusive future CCC plans. Comprehensive cancer control plans can serve as a key policy and advocacy structure to promote a focus on LGBTQ+ cancer prevention and control.

Clinical Outcomes from the Alaska Native Tribal Health Consortium Colorectal Cancer Control Program: 2009-2015.

The Alaska Native Tribal Health Consortium (ANTHC) participated in the United States Centers for Disease Control and Prevention Colorectal Cancer Control Program (CRCCP) from 2009 to 2015. We conducted a descriptive evaluation of ANTHC CRCCP demographics, quality measures, and clinical outcomes, including screening methods employed within the program and screening outcomes. There were 6981 program screenings completed, with the majority (81.3%) of people screened in the 50-75 year age group. Colonoscopy was the primary screening test used, accounting for 6704 (96.9%) of the screening tests. Quality of colonoscopy was high: adequate bowel preparation was reported in 98.2% of colonoscopies, cecal intubation rate was 98.9%, and the adenoma detection rate was 38.9%. A high proportion (58.9%) of colonoscopies had an initial finding of polyps or lesions suspicious for cancer; 41.2% of all colonoscopies had histological confirmation of either adenomatous polyps (40.6%) or cancer (0.5%). The ANTHC CRCCP successfully increased CRC screening among American Indian and Alaska Native peoples living in Alaska; this was achieved primarily through high-quality colonoscopy metrics. These data support a continued focus by the Alaska Native Tribal Health Consortium and its tribal health partners on increasing CRC screening and reducing cancer mortality among Alaska Native peoples.

Patient perspectives of weight stigma across the cancer continuum: A scoping review.

BACKGROUND: Weight stigma has been defined as the social devaluation and denigration of individuals because of their weight. The purpose of this scoping systematic review was to assess and understand patient experiences with weight stigma in the cancer care setting. METHODS: We conducted a systematic scoping review of studies examining shame, prejudice, bias, and stigma in relation to weight and cancer-related care using five databases: PubMed, CINAHL Plus Full Text (ProQuest), Cochrane Library, PsycINFO (EBSCO), and Scopus. Articles were uploaded into Covidence for de-duplication and screening. Included studies were peer reviewed, reported adult patient experiences in cancer-related care, and were published in English between October 2012 and February 2023. Study characteristics and key findings were abstracted and qualitatively synthesized. RESULTS: Publications meeting inclusion criteria yielded five studies (n = 113 participants). Most focused on the experiences of women (n = 4) and cancers which predominantly impact women (i.e., breast, cervical, endometrial; n = 4). All stages of the cancer continuum were included with studies examining screening (n = 2), treatment (n = 1), and post-treatment survivorship (n = 2). Weight discrimination was discussed in four studies and weight-biased stereotypes were discussed in three studies. Experiences of weight bias internalization were reported in four studies. One study described an instance of implicit weight bias. CONCLUSIONS: Limited studies examine patient experiences of weight stigma in cancer care; however, current evidence suggests that patients do experience weight stigma in cancer-related care. This review highlights critical gaps and a need for more research on the prevalence and impact of weight stigma in cancer screening and care.

Perspectives on Referring for Rectal Cancer Surgery: a Survey Study of Gastroenterologist and General Surgeons in Iowa.

PURPOSE: To understand referral practices for rectal cancer surgical care and to secondarily determine differences in referral practices by two main hypothesized drivers of referral: the rurality of the community endoscopists' practice and their affiliation with a colorectal surgeon. METHODS: Community gastroenterologists and general surgeons in Iowa completed a mailed questionnaire on practice demographics, volume, and referral practices for rectal cancer patients. Rurality was operationalized with RUCA codes. RESULTS: Twenty-two of 53 gastroenterologists (42%) and 120 of 188 general surgeons (64%) (total 144/241, 60%) in Iowa responded. Most performed colonoscopies, including 22 gastroenterologists (100%) and 96 general surgeons (80%). Regular referral of rectal cancer patients to colorectal surgeons was reported for 57% of urban physicians affiliated with a colorectal surgeon, 33% of urban physicians not affiliated with a colorectal surgeon, and 57% and 72% of physicians in large and small rural areas, respectively, who were not affiliated with a colorectal surgeon. High surgeon volume, high hospital volume, and colorectal surgeon specialty were important factors in the referral decisions for over half the physicians. 69% of diagnosing urban general surgeons reported performing rectal cancer surgery about half the time or more, while 85% of small rural and 60% of large rural diagnosing general surgeons reported never or rarely performing rectal cancer surgery. CONCLUSIONS: Diagnosing physicians have variable rectal cancer referral practices, including consistency in referred to surgeon and prioritization of volume and specialization. Prioritizing specialized or high-volume rectal cancer surgical care would require changing existing referring patterns.

The Carbon Stable Isotope Ratio as an Objective Biomarker of Added Sugar Intake: A Scoping Review of Current Evidence in Human Nutrition.

Objective biomarkers of dietary intake are needed to advance nutrition research. The carbon stable isotope ratio (C13/C12; CIR) holds promise as an objective biomarker of added sugar (AS) and sugar-sweetened beverage (SSB) intake. This systematic scoping review presents the current evidence on CIRs from human studies. Search results (through April 12, 2024) yielded 6297 studies and 24 final articles. Studies were observational (n = 12), controlled feeding (n = 10), or dietary interventions (n = 2). CIRs were sampled from blood (n = 23), hair (n = 5), breath (n = 2), and/or adipose tissue (n = 1). Most (n = 17) conducted whole tissue (that is, bulk) analysis, 8 used compound specific isotope analysis (CSIA), and/or 2 studies used methods appropriate for analyzing breath. Studies were conducted in 3 concentrated geographic regions of the United States (n = 7 Virginia; n = 5 Arizona; n = 4 Alaska), with only 2 studies conducted in other countries. Studies that used CSIA to examine the CIR from the nonessential amino acid alanine (CIR-Ala; n = 4) and CIR analyzed from breath (n = 2) provided the most robust evidence for CIR as an objective biomarker of AS and SSBs (R2 range 0.36-0.91). Studies using bulk analysis of hair or blood showed positive, but modest and more variable associations with AS and SSBs (R2 range 0.05-0.48). Few studies showed no association, particularly in non-United States populations and those with low AS and SSB intakes. Two studies provided evidence for CIR to detect changes in SSB intake in response to dietary interventions. Overall, the most compelling evidence supports CIR-Ala as an objective indicator of AS intake and breath CIR as an indicator of short-term AS intake. Considering how to adjust for underlying dietary patterns remains an important area of future work and emerging methods using breath and CSIA warrant additional investigation. More evidence is needed to refine the utility and specificity of CIRs to measure AS and SSB intake.

Identifying predictors of COVID-related delays in cancer-specific medical care.

PURPOSE: Evidence of the impact of the COVID-19 pandemic on cancer prevention and control is growing, but little is known about patient-level factors associated with delayed care. We analyzed data from a survey focused on Iowan cancer patients' COVID-19 experiences in the early part of the pandemic. METHODS: Participants were recruited from the University of Iowa Holden Comprehensive Cancer Center's Patients Enhancing Research Collaborations at Holden (PERCH) program. We surveyed respondents on demographic characteristics, COVID-19 experiences and reactions, and delays in any cancer-related health care appointment, or cancer-related treatment appointments. Two-sided significance tests assessed differences in COVID-19 experiences and reactions between those who experienced delays and those who did not. RESULTS: There were 780 respondents (26% response), with breast, prostate, kidney, skin, and colorectal cancers representing the majority of respondents. Delays in cancer care were reported by 29% of respondents. In multivariable-adjusted models, rural residents (OR 1.47; 95% CI 1.03, 2.11) and those experiencing feelings of isolation (OR 2.18; 95% CI 1.37, 3.47) were more likely to report any delay, where experiencing financial difficulties predicted delays in treatment appointments (OR 5.72; 95% CI 1.96, 16.67). Health insurance coverage and concern about the pandemic were not statistically significantly associated with delays. CONCLUSION: These findings may inform cancer care delivery during periods of instability when treatment may be disrupted by informing clinicians about concerns that patients have during the treatment process. Future research should assess whether delays in cancer care impact long-term cancer outcomes and whether delays exacerbate existing disparities in cancer outcomes.

Evidence-based screening, clinical care and health education recommendations for Alaska Native peoples with prediabetes living in southcentral Alaska: findings from the Alaska EARTH follow-up study.

Pre-diabetes (pre-DM) is a strong predictor of diabetes (DM) over time. This study investigated how much of the recent increase in pre-DM identified among Alaska Native (AN) peoples living in urban southcentral Alaska may be due to changes in diagnostic methods. We used clinical and demographic data collected at baseline between 2004 and 2006 and at follow-up collected between 2015 and 2017 from the urban southcentral Alaska Education and Research Towards Health (EARTH) cohort. We used descriptive statistics and logistic regression to explore differences in demographic and clinical variables among the identified pre-DM groups. Of 388 participants in the follow-up study, 243 had A1c levels indicating pre-DM with only 20 demonstrating pre-DM also by fasting blood glucose (FBG). Current smoking was the sole predictor for pre-DM by A1c alone while abdominal obesity and elevated FBG-predicted pre-DM by A1c+FBG. No participants had an elevated FBG without an A1c elevation. A substantial portion of the rise in pre-DM found among urban southcentral AN peoples in the EARTH follow-up study was due to the addition of A1c testing. Pre-DM by A1c alone should be used to motivate behavioural changes that address modifiable risk factors, including smoking cessation, physical activity and weight management.