Stage Shifting by Modifying the Determinants of Breast Cancer Stage at Diagnosis: A Simulation Study.

BACKGROUND: Breast cancer is the most common cancer in Canadian women; nearly 25% of women diagnosed with cancer have breast cancer. The early detection of breast cancer is a major challenge because tumours often grow without causing symptom. The diagnosis of breast cancer at an early stage (stages I and II) improves survival outcomes because treatments are more effective and better tolerated. To better inform the prevention of and screening for breast cancer, simulations using modifiable rather than non-modifiable risk factors may be helpful in shifting the stage at diagnosis downward. METHODS: Breast cancer stages were simulated using the data distributions from Alberta's Tomorrow Project participants who developed breast cancer. Using multivariable partial proportional odds regression models, modifiable lifestyle factors associated with the stage of cancer at diagnosis were evaluated. The proportions or mean levels of these lifestyle factors in the simulated population were systematically changed, then multiplied by their corresponding estimated odds ratios from the real data example. The effects of these changes were evaluated singly as well as cumulatively. RESULTS: Increasing total dietary protein (g/day) intake was the single most important lifestyle factor in shifting the breast cancer stage downwards followed by decreasing total dietary energy intake (kcal/day). Increasing the proportion of women who spend time in the sun between 11 am and 4 pm in the summer months, who have had a mammogram, who have been pregnant or reducing the proportion who are in stressful situations had much smaller effects. The percentage of Stage I diagnoses could be increased by approximately 12% with small modifications of these lifestyle factors. CONCLUSION: Shifting the breast cancer stage at diagnosis of a population may be achieved through changes to lifestyle factors. This proof of principle study that evaluated multiple factors associated with the stage at diagnosis in a population can be expanded to other cancers as well, providing opportunities for cancer prevention programs to target specific factors and identify populations at higher risk.

Creation of a Métis-Specific Instrument for Cancer Screening: A Scoping Review of Cancer-Screening Programs and Instruments.

Understanding the barriers to and facilitators of cancer screening programs among Indigenous populations remains limited. In the spirit of mutual respect, this co-led, collaborative project was carried out between the Métis Nation of Alberta and Screening Programs from Alberta Health Services (AHS). This scoping review assessed the cancer screening literature for available questionnaires and then identified themes and suitable questions for a Métis-specific cancer screening questionnaire. Literature searches on cervical, breast, and colorectal cancer screening programs and related concepts were conducted in electronic databases, including the Native Health Database, MEDLINE (Ovid), PsycINFO, PubMed, PubMed Central, CINAHL, MEDLINE (Ebsco), Psychology & Behavioral Sciences Collection, and Web of Science. Grey literature was collected from AHS Insite, Open Archives Initiative repository, American Society of Clinical Oncology, European Society of Medical Oncology, Google, and Google Scholar. 135 articles were screened based on the eligibility criteria with 114 articles selected, including 14 Indigenous-specific ones. Knowledge, attitude, belief, behaviour, barrier, and facilitator themes emerged from the review, but no Métis-specific cancer screening instruments were found. Thus, one was developed using existing cancer screening instruments, with additional questions created by the project team. A survey of the Métis population in Alberta will use this questionnaire and provide data to address the burden of cancer among Métis people.

Plasma hPG80 (Circulating Progastrin) as a Novel Prognostic Biomarker for early-stage breast cancer in a breast cancer cohort.

BACKGROUND: Recurrence and metastases are still frequent outcomes after initial tumour control in women diagnosed with breast cancer. Although therapies are selected based on tumour characteristics measured at baseline, prognostic biomarkers can identify those at risk of poor outcomes. Circulating progastrin or hPG80 was found to be associated with survival outcomes in renal and hepatocellular carcinomas and was a plausible prognostic biomarker for breast cancer. METHODS: Women with incident breast cancers from Calgary, Alberta, Canada enrolled in the Breast to Bone (B2B) study between 2010 to 2016 and provided blood samples prior to any treatment initiation. Plasma from these baseline samples were analysed for circulating progastrin or hPG80. Participant characteristics as well as tumour ones were evaluated for their association with hPG80 and survival outcomes (time to recurrence, recurrence - free survival, breast cancer specific survival and overall survival) in Cox proportional hazards regression models. RESULTS: The 464 participants with measurable hPG80 in this study had an average age of 57.03 years (standard deviation of 11.17 years) and were predominantly diagnosed with Stage I (52.2%) and Stage II (40.1%) disease. A total of 50 recurrences and 50 deaths were recorded as of June 2022. In Cox PH regression models adjusted for chemotherapy, radiation therapy, cancer stage and age at diagnosis, log hPG80 (pmol/L) significantly increased the risks for recurrence (Hazard Ratio (HR) = 1.330, 95% Confidence Interval (CI) = (0.995 - 1.777, p = 0.054)), recurrence-free survival (HR = 1.399, 95% CI = (1.106 - 1.770), p = 0.005) and overall survival (HR = 1.385, 95% CI = (1.046 - 1.834), = 0.023) but not for breast cancer specific survival (HR = 1.015, 95% CI = (0.684 - 1.505), p = 0.942). CONCLUSIONS: hPG80 levels measured at diagnosis were significantly associated with the risk of recurrence or death from any cause in women with breast cancer. Since the recurrence rates of breast cancer are still relatively high amongst women diagnosed at an early stage, identifying women at high risk of recurrence at their time of diagnosis is important. hPG80 is a promising new prognostic biomarker that could improve the identification of women at higher risk of poor outcomes.

Meta-analysis of NAD(P)(H) quantification results exhibits variability across mammalian tissues.

Nicotinamide Adenine Dinucleotide (NAD+) plays an important role in energy metabolism and signaling pathways controlling crucial cellular functions. The increased interest in NAD+ metabolism and NAD+-boosting therapies has reinforced the necessity for accurate NAD+ quantification. To examine the published NAD(P)(H) measures across mammalian tissues, we performed a meta-analysis of the existing data. An Ovid MEDLINE database search identified articles with NAD(P)(H) quantification results obtained from mammalian tissues published between 1961 and 2021. We screened 4890 records and extracted quantitative data, as well as the quantification methods, pre-analytical conditions, and subject characteristics. The extracted physiological NAD(P)(H) concentrations in various tissues from mice, rats, and humans, revealed an important inter- and intra-method variability that extended to recent publications. This highlights the relatively poor potential for cross-experimental analyses for NAD(P)(H) quantitative data and the importance of standardization for NAD(P)(H) quantification methods and pre-analytical procedures for future preclinical and clinical studies.