To develop and validate a histopathologic scoring system for measuring response to neoadjuvant chemotherapy in interval debulking surgery specimens of stage IIIC to IV tubo-ovarian high-grade serous ...carcinoma.
A six-tier histopathologic scoring system was proposed and applied to a test cohort (TC) of 62 patients treated with neoadjuvant chemotherapy and interval debulking surgery. Adnexal and omental sections were independently scored by three pathologists. On the basis of TC results, a three-tier chemotherapy response score (CRS) system was developed and applied to an independent validation cohort of 71 patients.
The initial system showed moderate interobserver reproducibility and prognostic stratification of TC patients when applied to the omentum but not to the adnexa. Condensed to a three-tier score, the system was highly reproducible (kappa, 0.75). When adjusted for age, stage, and debulking status, the score predicted progression-free survival (PFS; score 2 v 3; median PFS, 11.3 v 32.1 months; adjusted hazard ratio, 6.13; 95% CI, 2.13 to 17.68; P < .001). The three-tier CRS system applied to omental samples from the validation cohort showed high reproducibility (kappa, 0.67) and predicted PFS (CRS 1 and 2 v 3: median, 12 v 18 months; adjusted hazard ratio, 3.60; 95% CI, 1.69 to 7.66; P < .001). CRS 3 also predicted sensitivity to first-line platinum therapy (94.3% negative predictive value for progression < 6 months). A Web site was established to train pathologists to use the CRS system.
The CRS system is reproducible and shows prognostic significance for high-grade serous carcinoma. Implementation in international pathology reporting has been proposed by the International Collaboration on Cancer Reporting, and the system could potentially have an impact on patient care and research.
Gel-forming mucins, the primary macromolecular components of airway mucus, facilitate airway clearance by mucociliary transport. In cystic fibrosis (CF) altered mucus properties impair mucociliary ...transport. Airways primarily secrete two closely related gel-forming mucins, MUC5B and MUC5AC. However, their morphologic structures and associations in airways that contain abundant submucosal glands and goblet cells are uncertain. Moreover, there is limited knowledge about mucins in airways not affected by inflammation, infection, or remodeling or in CF airways. Therefore, we examined airways freshly excised from newborn non-CF pigs and CF pigs before secondary manifestations develop. We found that porcine submucosal glands produce MUC5B, whereas goblet cells produce predominantly MUC5AC plus some MUC5B. We found that MUC5B emerged from submucosal gland ducts in the form of strands composed of multiple MUC5B filaments. In contrast, MUC5AC emerged from goblet cells as wispy threads and sometimes formed mucin sheets. In addition, MUC5AC often partially coated the MUC5B strands. Compared with non-CF, MUC5B more often filled CF submucosal gland ducts. MUC5AC sheets also accumulated in CF airways overlying MUC5B strands. These results reveal distinct morphology and interactions for MUC5B and MUC5AC and suggest that the two mucins make distinct contributions to mucociliary transport. Thus, they provide a framework for understanding abnormalities in disease.
Research suggests pets foster affection, connection, and physical activity, yet has failed to address the challenges people diagnosed with cancer face in caring for their pets. The objective of this ...study was to better understand how pets serve as emotional buffers and/or stressors for people diagnosed with breast cancer, and how their ability to meet their pet's needs affects their well-being.
A cross-section study of people diagnosed with breast cancer in the United States was conducted. Adults diagnosed with stages 0 (in situ) -IV breast cancer and currently the primary guardian of at least one dog or cat and owned the animal(s) for at least 6 months, were recruited for the study. A total of 211 responses, obtained between July - November 2022 were analyzed. The survey included questions about participants' demographics; attachment to their pets; physical, emotional, and functional well-being; social support received from their pet; and 'pet parenting' concerns. Descriptive statistics were calculated to describe participants' demographics. Multiple regression analyses were conducted to determine predictors of pet attachment, well-being, support from pet, and 'pet parenting' concerns.
People diagnosed with breast cancer derive substantial support from their pets (80% feel their pet makes them feel loved, needed, and offers a positive presence in the home), yet only 50% of participants feel this relationship is supported by their medical team. Controlling for owner demographics, heightened levels of pet-related guilt and concerns, along with lower perceived support from their pet, are all significant predictors of a lower quality of life.
Findings highlight the benefits pets offer people diagnosed with breast cancer, yet also the distress they feel in trying to meet their pet's needs. Assessment conversations about pet ownership, including pet-related support systems, are needed to validate people's concerns and support the identification and development of pet support teams. Medical team facilitated discussions about pet care needs is suggested to demonstrate support for the pet-parent bond and help normalize feelings of guilt related to challenges in meeting their pet's needs. These discussions could be aided through the development of research-driven intervention strategies and online, freely accessible targeted tools.
The aim of this study was to evaluate associations between pre- and postdiagnosis physical activity and survival in survivors of endometrial cancer by physical activity domain, intensity, dose ...(metabolic-equivalent task MET-hours/week/year), and change from pre- to postdiagnosis.
We conducted a prospective cohort study in Alberta, Canada, of 425 women who were diagnosed with histologically confirmed invasive endometrial cancer between 2002 and 2006 and observed to 2019. The interviewer-administered Lifetime Total Physical Activity Questionnaire recorded prediagnosis (assessed at a median of 4.4 months after diagnosis) and postdiagnosis physical activity (assessed at a median of 3.4 years after diagnosis). Associations between physical activity and overall and disease-free survival were assessed using Cox proportional hazards models adjusted for age, stage, grade, treatments, body mass index, menopausal status, hormone therapy use, family history of cancer, and comorbidities.
After a median follow-up of 14.5 years, there were 60 deaths, including 18 endometrial cancer deaths, and 80 disease-free survival events. Higher prediagnosis recreational physical activity was statistically significantly associated with improved disease-free survival (> 14
≤ 8 MET-hours/week/year; hazard ratio HR, 0.54; 95% CI, 0.30 to 0.96;
= .04), but not overall survival (HR, 0.56; 95% CI, 0.29 to 1.07;
= .06). Higher postdiagnosis recreational physical activity (> 13
≤ 5 MET-hours/week/year) was strongly associated with both improved disease-free survival (HR, 0.33; 95% CI, 0.17 to 0.64;
= .001) and overall survival (HR, 0.33; 95% CI, 0.15 to 0.75;
= .007). Participants who maintained high recreational physical activity levels from pre- to postdiagnosis also had improved disease-free survival (HR, 0.35; 95% CI, 0.18 to 0.69) and overall survival (HR, 0.43; 95% CI, 0.20 to 0.94) compared with those who maintained low physical activity levels.
Recreational physical activity, especially postdiagnosis, is associated with improved survival in survivors of endometrial cancer.
Epithelial ovarian cancer (EOC) consists of 5 major histotypeshigh-grade serous carcinoma (HGSC), endometrioid carcinoma (EC), clear cell carcinoma (CCC), mucinous carcinoma (MC), and low-grade ...serous carcinoma (LGSC). Each can have a broad spectrum of morphologic appearances, and 1 histotype can closely mimic histopathologic features more typical of another. Historically, there has been a relatively high frequency of mixed, defined by 2 or more distinct histotypes present on the basis of routine histopathologic assessment, histotype carcinoma diagnoses (3% to 11%); however, recent immunohistochemical (IHC) studies identifying histotype-specific markers and allowing more refined histotype diagnoses suggest a much lower incidence. We reviewed hematoxylin and eosin–stained slides from 871 cases of EOC and found the frequency of mixed carcinomas to be 1.7% when modern diagnostic criteria are applied. Through international collaboration, we established a cohort totaling 22 mixed EOCs, consisting of 9 EC/CCC, 4 EC/LGSC, 3 HGSC/CCC, 2 CCC/MC, and 4 other combinations. We interrogated the molecular differences between the different components of each case using IHC, gene expression, and hotspot sequencing analyses. IHC data alone suggested that 9 of the 22 cases were not mixed tumors, as they presented a uniform immuno-phenotype throughout, and these cases most probably represent morphologic mimicry and variation within tumors of a single histotype. Synthesis of molecular data further reduces the incidence of mixed carcinomas. On the basis of these results, true mixed carcinomas with both morphologic and molecular support for the presence of >1 histotype within a given tumor represent <1% of EOCs.
Abstract
Background
Disease-free survival (DFS) and overall survival (OS) associations with anthropometric measures of obesity and changes in these exposures remain unknown among endometrial cancer ...survivors.
Methods
Endometrial cancer survivors diagnosed between 2002 and 2006 completed direct anthropometric measurements and self-reported lifetime weight history during in-person interviews approximately 4 months after diagnosis (peridiagnosis) and approximately 3 years after diagnosis (follow-up). Participants were followed-up until death or March 20, 2019. Cox proportional regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for body mass index (BMI), weight, waist circumference, and waist-hip ratio with DFS and OS. Statistical tests were 2-sided.
Results
A total of 540 and 425 cancer survivors were assessed peridiagnosis and follow-up, respectively. During the median 14.2 years of follow-up (range = 0.3-16.5 years), 132 participants had a recurrence and/or died (DFS), with 111 deaths overall (OS). Reduced DFS was noted with greater recalled weight 1 year before diagnosis (HR = 1.88, 95% CI = 1.15 to 3.07), BMI 1 year before diagnosis (HR = 1.88, 95% CI = 1.09 to 3.22), and measured peridiagnosis BMI (HR = 2.04, 95% CI = 1.18 to 3.53). Measured peridiagnosis waist circumference of at least 88 cm was associated with decreased DFS (HR = 1.94, 95% CI = 1.24 to 3.03) and OS (HR = 1.90, 95% CI = 1.16 to 3.13). A twofold decrease in DFS and OS was associated with a BMI of at least 5% or weight change from 1 year before diagnosis to peridiagnosis. No associations were observed for the assessment during follow-up.
Conclusions
One-year before- and peridiagnosis anthropometric measures of obesity were associated with reduced survival among endometrial cancer survivors. Anthropometric changes from 1 year before to peridiagnosis may provide an important indication of future survival in this population.
The prognostic relationship between diet and endometrial cancer survival remains largely unknown. We sought to determine pre- and post-diagnosis dietary composition, glycemic load (GL), inflammatory ...potential (dietary inflammatory index) and quality Canadian Healthy Eating Index (C-HEI) 2005 associations with disease-free (DFS) and overall survival (OS) among endometrial cancer survivors. In addition, we assessed associations between dietary changes with OS and explored obesity/physical activity effect modification.
Survivors, diagnosed in Alberta, Canada between 2002 and 2006, completed past-year, food-frequency questionnaires at-diagnosis (n = 503) and 3-year follow-up (n = 395). Participants were followed to death or January 2022. Cox proportional regression estimated HR 95% confidence intervals (CI) for dietary survival associations.
During 16.9 median years of follow-up, 138 participants had a DFS event and 120 died. Lower pre-diagnosis GL (HRT1vsT3, 0.49; 95% CI, 0.25-0.97) and greater post-diagnosis energy intakes (EI) from total- and monounsaturated-fat (HRT3vsT1, 0.48; 95% CI, 0.26-0.87) were associated with better OS. Higher pre-diagnosis C-HEI, less inflammatory diets and lower added sugar intakes were nonlinearly associated with better DFS. Consistently low pre- to post-diagnosis EI from carbohydrates and total-fats were associated with better (HR, 0.36; 95% CI, 0.18-0.72) and worse (HR, 2.26; 95% CI, 1.21-4.20) OS, respectively. Decreased pre- to post-diagnosis C-HEI was associated with worse OS. In stratified analysis, healthy diets were most beneficial for survivors with obesity and physical inactivity.
Adherence to higher quality dietary patterns were associated with better survival.
Our study provides novel evidence that both pre- and post-diagnosis diet are important prognostic factors for endometrial cancer survivors. Post-diagnosis survival associations with diet composition and quality highlight the potential for future interventions.
Type II diabetes and certain diabetes treatments have been observed to impact breast cancer risk. However, their associations with different breast cancer molecular subtype defined by estrogen ...receptor (ER)/progesterone receptor (PR)/HER2 status are unclear.
We conducted a retrospective multi-center population-based case-case study consisting of 4,557 breast cancer cases to evaluate the impact of type II diabetes and diabetes medications on the risk of different breast cancer molecular subtypes ER
/HER2
, ER
/HER2
, triple negative (ER
/PR
/HER2
), and HER2 overexpressing (H2E, ER
/PR
/HER2
). Using ER
/HER2
cases as the reference group, we estimated ORs and corresponding 95% confidence intervals (CI) for each subtype using polytomous logistic regression.
Compared with those without a diabetes history, women with type II diabetes had a 38% (95% CI, 1.01-1.89) increased odds of triple-negative breast cancer (TNBC). Current and longer term recent metformin use (13-24 months of treatment within the 24-month period prior to breast cancer diagnosis) was associated with elevated odds of TNBC (OR = 1.54; 95% CI, 1.07-2.22 and OR = 1.80; 95% CI, 1.13-2.85, respectively).
The odds of having a triple-negative rather than ER
/HER2
breast cancer is greater for women with type II diabetes, and particularly for those who were users of metformin. This finding is supported by some preclinical data suggesting that diabetes may be more strongly associated with risk of triple-negative disease.
Our study provides novel evidence regarding potential differential effects of type II diabetes and metformin use on risk of different molecular subtypes of breast cancer.
PDF
