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There is growing awareness of the unique etiology, biology, and clinical presentation of invasive lobular breast cancer (ILC), but additional research is needed to ensure translation of findings into management and treatment guidelines. We conducted a survey with input from breast cancer physicians, laboratory-based researchers, and patients to analyze the current understanding of ILC, and identify consensus research questions. 1774 participants from 66 countries respondents self-identified as clinicians (N = 413), researchers (N = 376), and breast cancer patients and advocates (N = 1120), with some belonging to more than one category. The majority of physicians reported being very/extremely (41%) to moderately (42%) confident in describing the differences between ILC and invasive breast cancer of no special type (NST). Knowledge of histology was seen as important (73%) and as affecting treatment decisions (51%), and most agreed that refining treatment guidelines would be valuable (76%). 85% of clinicians have never powered a clinical trial to allow subset analysis for histological subtypes, but the majority would consider it, and would participate in an ILC clinical trials consortium. The majority of laboratory researchers, reported being and very/extremely (48%) to moderately (29%) confident in describing differences between ILC and NST. They reported that ILCs are inadequately presented in large genomic data sets, and that ILC models are insufficient. The majority have adequate access to tissue or blood from patients with ILC. The majority of patients and advocates (52%) thought that their health care providers did not sufficiently explain the unique features of ILC. They identified improvement of ILC screening/early detection, and identification of better imaging tools as top research priorities. In contrast, both researchers and clinicians identified understanding of endocrine resistance and identifying novel drugs that can be tested in clinical trials as top research priority. In summary, we have gathered information from an international community of physicians, researchers, and patients/advocates that we expect will lay the foundation for a community-informed collaborative research agenda, with the goal of improving management and personalizing treatment for patients with ILC.

The roles of sex hormones such as estradiol, testosterone, and sex hormone-binding globulin (SHBG) in the etiology of lung and colorectal cancers in women, among the most common cancers after breast cancer, are unclear. This Mendelian randomization (MR) study evaluated such potential causal associations in women of European ancestry. We used summary statistics data from genome-wide association studies on sex hormones and from the Trøndelag Health Study (HUNT) and large consortia on cancers. There was suggestive evidence of 1-standard deviation increase in total testosterone levels being associated with a lower risk of lung non-adenocarcinoma (hazard ratio 0.60, 95% confidence interval 0.37–0.98) in the HUNT Study. However, this was not confirmed by using data from a larger consortium. In general, we did not find convincing evidence to support a causal role of sex hormones on risk of lung and colorectal cancers in women of European ancestry. [ABSTRACT FROM AUTHOR]

Background: Preclinical evidence suggests improved breast cancer survival associated with statin use, but findings from observational studies are conflicting and remain inconclusive. The objective of this study was to assess the association between statin use after cancer diagnosis and cancer outcomes among breast cancer patients. Methods: In this retrospective cohort study, 38,858 women aged ≥66 years who were diagnosed with localized and regional stage breast cancer from 2008 through 2017 were identified from the linked Surveillance, Epidemiology, and End Results Medicare database. Statin use was ascertained from Medicare Part D pharmacy claims data. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post‐diagnosis statin use and risks of breast cancer recurrence and breast cancer–specific mortality. Results: Over a median follow‐up of 2.9 years for recurrence and 3.7 years for mortality, 1446 women experienced a recurrence, and 2215 died from breast cancer. The mean duration of post‐diagnosis statin use was 2.2 years. Statin use post‐diagnosis was not associated with recurrence risk (HR, 1.05; 95% CI, 0.91–1.21), but was associated with a reduced risk of cancer‐specific mortality (HR, 0.85; 95% CI, 0.75–0.96). The reduction was more pronounced in women with hormone receptor–positive/human epidermal growth factor receptor 2–negative breast cancer (HR, 0.71; 95% CI, 0.57–0.88). Conclusions: These findings suggest that post‐diagnosis statin use is associated with improved cancer‐specific survival in women with breast cancer and should be confirmed in randomized trials of statin therapy in breast cancer patients. Statin use after cancer diagnosis is associated with improved cancer survival in a large cohort of elderly women with breast cancer, highlighting the potential of statins as anticancer agents in improving breast cancer outcomes. [ABSTRACT FROM AUTHOR]

Background Lack of diversity in the cancer research workforce persists, which the new requirement for all National Cancer Institute (NCI)–designated cancer centers to have a Plan to Enhance Diversity (PED) seeks to address. However, it is not well understood how different cancer centers are approaching the development and execution of these plans. Our objective was to assess how cancer centers are establishing and pursuing their PED. Methods We conducted a cross-sectional survey of members of the Cancer Center Diversity, Equity and Inclusion Network, which includes all NCI-designated cancer centers and several emerging centers. A total of 62 cancer centers (75% of those invited), including 58 NCI-designated cancer centers (81% of those with this designation), participated and completed a questionnaire that assessed PED leadership, major challenges, implementation strategies, and approach to evaluate PED progress. Results The most common PED challenge identified is recruiting diverse faculty (68% of centers), and the most common strategy currently used to address this is reviewing and revising faculty recruitment practices (67%). The most common approach centers are using to measure PED progress is shifts in demographics (68%), and data on the demographics of faculty, leadership, and trainees are available at 79%, 81%, and 75% of centers, respectively. Conclusions Almost all centers have established a PED leadership structure, however, there is considerable variation in the approaches used to realize PED goals and in the resources provided to support PED work. Realizing opportunities to share and implement common best practices and exemplar programs has the potential to elevate the impact of PED efforts nationally. [ABSTRACT FROM AUTHOR]

African-ancestry (AA) participants are underrepresented in genetics research. Here, we conducted a transcriptome-wide association study (TWAS) in AA female participants to identify putative breast cancer susceptibility genes. We built genetic models to predict levels of gene expression, exon junction, and 3′ UTR alternative polyadenylation using genomic and transcriptomic data generated in normal breast tissues from 150 AA participants and then used these models to perform association analyses using genomic data from 18,034 cases and 22,104 controls. At Bonferroni-corrected P < 0.05, we identified six genes associated with breast cancer risk, including four genes not previously reported (CTD-3080P12.3, EN1, LINC01956 and NUP210L). Most of these genes showed a stronger association with risk of estrogen-receptor (ER) negative or triple-negative than ER-positive breast cancer. We also replicated the associations with 29 genes reported in previous TWAS at P < 0.05 (one-sided), providing further support for an association of these genes with breast cancer risk. Our study sheds new light on the genetic basis of breast cancer and highlights the value of conducting research in AA populations. Here, the authors integrate genomic and transcriptomic data obtained from African-ancestry female participants and identify six genes associated with breast cancer risk which provides biological insights into this common cancer in an underrepresented population. [ABSTRACT FROM AUTHOR]

Background Risk factors for cancer-related fatigue are understudied in colorectal cancer. Purpose This study aimed to address this critical gap in the literature by (a) describing changes in colorectal cancer-related fatigue and health behavior (physical activity, sleep problems) and (b) examining if physical activity and sleep problems predict fatigue trajectories from baseline (approximately at the time of diagnosis), to 6- and 12 months after enrollment. Methods Patients participating in the international ColoCare Study completed self-report measures at baseline (approximately time of diagnosis), 6-, and 12 months assessing physical activity using the International Physical Activity Questionnaire (IPAQ) and fatigue and sleep using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). Mixed-effect models examined changes in physical activity, sleep problems, and fatigue. Cross-lagged panel models examined bidirectional relationships between physical activity or sleep and fatigue across time. Results Colorectal cancer patients (n = 649) had a mean age of 61 ± 13 years. Most were male (59%), non-Hispanic White (91%), diagnosed with Stages III–IV (56%) colon cancer (58%), and treated with surgery (98%). Within-person cross-lagged models indicated higher physical activity at Month 6 was associated with higher fatigue at Month 12 (β = 0.26, p =.016). When stratified by cancer stage (I–II vs. III–IV), the relationship between physical activity at Month 6 and fatigue at Month 12 existed only for patients with advanced cancer (Stages III and IV, β = 0.43, p =.035). Cross-lagged associations for sleep and fatigue from baseline to Month 6 were only observed in patients with Stages III or IV cancer, however, there was a clear cross-sectional association between sleep problems and fatigue at baseline and Month 6. Conclusions Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced colorectal cancer the first year after diagnosis. In addition, sleep problems were consistently associated with higher fatigue in the first year, regardless of cancer stage. Trial registration The international ColoCare Study was registered on clinicaltrials.gov, NCT02328677, in December 2014. [ABSTRACT FROM AUTHOR]

Background: This study evaluates the relationship between smoking, alcohol, and breast cancer outcomes according to molecular subtype. Methods: This population-based prospective cohort consisted of 3,876 women ages 20 to 69 diagnosed with a first primary invasive breast cancer from 2004 to 2015 in the Seattle-Puget Sound region. Breast cancer was categorized into three subtypes based on estrogen receptor (ER), progesterone receptor (PR), and HER2 expressions: luminal (ER+), triple-negative (TN; ER-/PR-/HER2-), and HER2-overexpressing (H2E; ER-/HER2+). We fit Cox proportional hazards models to assess the association between alcohol consumption and smoking status at diagnosis and risks of recurrence, breast cancer-specific mortality, and all-cause mortality. Results: Histories of ever smoking [HR, 1.33; 95% confidence interval (CI), 1.01-1.74] and current smoking (HR, 1.59; 95% CI, 1.07-2.35) were associated with greater risk of breast cancer recurrence among TN cases. Smoking was also associated with greater risk of recurrence to bone among all cases and among luminal cases. Elevated risks of breast cancer-specific and all-cause mortality were observed among current smokers across all subtypes. Alcohol use was not positively associated with risk of recurrence or mortality overall; however, TN patients who drank four or more drinks per week had a decreased risk of recurrence (HR, 0.71; 95% CI, 0.51-0.98) and breast cancer-specific mortality (HR, 0.73; 95% CI, 0.55-0.97) compared with non-current drinkers. Conclusions: Patients with breast cancer with a history of smoking at diagnosis have elevated risks of recurrence and mortality. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Despite increased recognition that structural racism contributes to poorer health outcomes for racial and ethnic minorities, there are knowledge gaps about how current patterns of racial residential segregation are associated with cancer screening uptake. The authors examined associations between Black residential segregation and screening for colorectal cancer (CRC) and cervical cancer among non‐Hispanic Black and non‐Hispanic White adults.This was a retrospective study of CRC and cervical cancer screening‐eligible adults from five health care systems within the Population‐Based Research to Optimize the Screening Process (PROSPR II) Consortium (cohort entry, 2010–2012). Residential segregation was measured using site‐specific quartiles of the Black local isolation score (LIS). The outcome was receipt of CRC or cervical cancer screening within 3 years of cohort entry (2010–2015). Logistic regression was used to calculate associations between the LIS and screening completion, adjusting for patient‐level covariates.Among CRC (n = 642,661) and cervical cancer (n = 163,340) screening‐eligible patients, 456,526 (71.0%) and 106,124 (65.0%), respectively, received screening. Across PROSPR sites, living in neighborhoods with higher LIS tended to be associated with lower odds of CRC screening (Kaiser Permanente Northern California: adjusted odds ratio [aOR] LIS trend in Black patients, 0.95 [p < .001]; aOR LIS trend in White patients, 0.98 [p < .001]; Kaiser Permanente Southern California: aOR LIS trend in Black patients, 0.98 [p = .026]; aOR LIS trend in White patients, 1.01 [p = .023]; Kaiser Permanente Washington: aOR LIS trend in White patients, 0.97 [p = .002]. However, for cervical cancer screening, associations with the LIS varied by site and race (Kaiser Permanente Washington: aOR LIS trend in White patients, 0.95 [p < .001]; Mass General Brigham: aOR LIS trend in Black patients, 1.12 [p < .001]; aOR LIS trend in White patients, 1.03 [p < .001]).Across five diverse health care systems, the direction of the association between Black residential segregation and screening varied by PROSPR site, race, and screening type. Additional research, including studies that examine multiple dimensions of segregation and structural racism using intersectional approaches, are needed to further disentangle these relationships. [ABSTRACT FROM AUTHOR]

Background: We evaluated the association between metabolic syndrome (obesity plus two metabolic risk factors) and breast cancer outcomes according to molecular subtype., Methods: This population-based prospective cohort consisted of 3,267 women aged 20-69 diagnosed with a first primary invasive breast cancer from 2004-2015 in the Seattle-Puget Sound region. Breast cancer was categorized into three subtypes based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression: luminal (ER+), triple-negative (ER-/PR-/HER2-), and HER2-overexpressing (H2E) (ER-/HER2+). We used time-varying Cox models to assess the association between prevalent and incident metabolic syndrome and risks of recurrence, breast cancer-specific mortality, and all-cause mortality., Results: Metabolic syndrome was associated with a greater risk of recurrence (HR:3.24; 95% CI:1.13-9.33) and breast cancer-specific mortality (HR:5.34; 95% CI:2.32-12.31) only for the H2E subtype, and greater risks of all-cause mortality for luminal (HR:1.92; 95% CI:1.37-2.68), H2E (HR:5.09; 95% CI:2.51-10.32), and all cases combined (HR:1.90; 95% CI:1.42,2.53). We also observed heterogeneity in recurrence and mortality outcomes across specific components of metabolic syndrome and molecular subtypes., Conclusions: Metabolic syndrome is associated with all-cause mortality among women with breast cancer and with breast cancer-specific mortality among women with the H2E subtype., Impact: These results highlight the importance of managing comorbidities to decrease the risk for adverse outcomes among breast cancer survivors.

Cancer is pervasive across multicellular species, but what explains the differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades of tetrapods (amphibians, sauropsids, and mammals), we found that neoplasia and malignancy prevalence increases with adult mass (contrary to Peto's paradox) and somatic mutation rate but decreases with gestation time. The relationship between adult mass and malignancy prevalence was only apparent when we controlled for gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%), the black-footed penguin (<0.4%), ferrets (63%), and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer. Significance: Evolution has discovered mechanisms for suppressing cancer in a wide variety of species. By analyzing veterinary necropsy records, we can identify species with exceptionally high or low cancer prevalence. Discovering the mechanisms of cancer susceptibility and resistance may help improve cancer prevention and explain cancer syndromes., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Findings from studies investigating the impacts of alcohol use and smoking on colorectal cancer (CRC) outcomes are inconclusive. This study aimed to investigate associations between alcohol use and smoking status at the time of diagnosis on recurrence and overall mortality among patients with CRC., Methods: The present study included 2,216 stage I-IV patients with CRC from the longitudinal multi-center ColoCare study, with available data on recurrence and CRC-specific mortality. Cox proportional hazards models adjusted for age, sex, race, ethnicity, stage, tumor site, treatment, comorbidities, body mass index, and study site were fit, with imputations for missing data., Results: We observed 235 recurrences and 308 CRC-specific deaths over an average of 3 years of follow-up. After adjusting for confounders, current alcohol consumption and ever smoking, relative to not current consumption and never smoking, respectively, were not statistically significantly associated with CRC recurrence (Alcohol - HR: 0.95. 95% CI: 0.71-1.29; Ever smoking - HR: 0.98, 95% CI: 0.75-1.29) or CRC-specific mortality (Alcohol - HR: 0.95. 95% CI: 0.74-1.22; Ever smoking - HR: 0.98, 95% CI: 0.77-1.24)., Conclusions: No associations were observed between alcohol and smoking at diagnosis and clinical outcomes in this well-annotated longitudinal cohort., Impact: Our cohort study reports no significant associations; however, limiting alcohol use and avoiding smoking are health behaviors recommended for CRC survivors for prevention of other cancers and chronic conditions.

Alterations within the tryptophan-kynurenine metabolic pathway have been linked to the etiology of colorectal cancer (CRC), but the relevance of this pathway for prognostic outcomes in CRC patients needs further elucidation. Therefore, we investigated associations between circulating concentrations of tryptophan-kynurenine pathway metabolites and all-cause mortality among CRC patients. This study utilizes data from 2102 stage I-III CRC patients participating in six prospective cohorts involved in the international FOCUS Consortium. Preoperative circulating concentrations of tryptophan, kynurenine, kynurenic acid (KA), 3-hydroxykynurenine (HK), xanthurenic acid (XA), 3-hydroxyanthranilic acid (HAA), anthranilic acid (AA), picolinic acid (PA), and quinolinic acid (QA) were measured by liquid chromatography-tandem mass spectrometry. Using Cox proportional hazards regression, we examined associations of above-mentioned metabolites with all-cause mortality, adjusted for potential confounders. During a median follow-up of 3.2 years (interquartile range: 2.2-4.9), 290 patients (13.8%) deceased. Higher blood concentrations of tryptophan, XA, and PA were associated with a lower risk of all-cause mortality (per doubling in concentrations: tryptophan: HR = 0.56; 95%CI:0.41,0.76, XA: HR = 0.74; 95%CI:0.64,0.85, PA: HR = 0.76; 95%CI:0.64,0.92), while higher concentrations of HK and QA were associated with an increased risk of death (per doubling in concentrations: HK: HR = 1.80; 95%CI:1.47,2.21, QA: HR = 1.31; 95%CI:1.05,1.63). A higher kynurenine-to-tryptophan ratio, a marker of cell-mediated immune activation, was associated with an increased risk of death (per doubling: HR = 2.07; 95%CI:1.52,2.83). In conclusion, tryptophan-kynurenine pathway metabolites may be prognostic markers of survival in CRC patients., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)