Background Breast cancer has distinct causes, prognoses, and outcomes and effects in patients at premenopausal and postmenopausal ages. We sought to assess the global burden and trends in breast cancer by menopausal status. MethodsWe did a population-based analysis of global breast cancer incidence and mortality among premenopausal and postmenopausal women. Menopausal status was defined using age as a proxy, whereby breast cancer cases or deaths at age 50 years or older were regarded as postmenopausal. Age-standardised breast cancer incidence and mortality in 2018 were calculated using GLOBOCAN data. Incidence trends for 1998-2012 were assessed in 44 populations from 41 countries using the Cancer in Five Continents plus database, by calculating the annual average percent change.Findings Approximately 645 000 premenopausal and 1•4 million postmenopausal breast cancer cases were diagnosed worldwide in 2018, with more than 130 000 and 490 000 deaths occurring in each menopausal group, respectively. Proportionally, countries with a low UNDP human development index (HDI) faced a greater burden of premenopausal breast cancer for both new cases and deaths compared with higher income countries. Countries with a very high HDI had the highest premenopausal and postmenopausal breast cancer incidence (30•6 and 253•6 cases per 100 000, respectively), whereas countries with low and medium HDI had the highest premenopausal and postmenopausal mortality, respectively (8•5 and 53•3 deaths per 100 000, respectively). When examining breast cancer trends, we noted significantly increasing age-standardised incidence rates (ASIRs) for premenopausal breast cancer in 20 of 44 populations and significantly increasing ASIRs for postmenopausal breast cancer in 24 of 44 populations. The growth exclusively at premenopausal ages largely occurred in high-income countries, whereas the increasing postmenopausal breast cancer burden was most notable in countries under transition.Interpretation We provide evidence of a rising burden of both premenopausal and postmenopausal breast cancer worldwide. Although early diagnosis and access to treatment remain crucial in low-income and middle-income countries, primary prevention efforts seeking to decrease exposure to known breast cancer risk factors are warranted in all world regions to curb the future breast cancer burden.

Key Points Question Is the incidence of colorectal cancer among younger adults still increasing in Canada? Findings This cohort study used data from comprehensive Canadian national cancer registries and included all 688 515 incident colorectal cancers diagnosed from 1969 to 2015. The incidence of colorectal cancer among younger adults increased from 2006 to 2015 among men with an annual percentage change of 3.47% and from 2010 to 2015 among women with an annual percentage change of 4.45%. Meaning These results provide evidence that the increased incidence of colorectal cancer among younger adults in Canada is continuing and possibly accelerating.

BACKGROUND: Recent studies have identified increases in cancer incidence among younger adults for some cancers. This study examined incidence trends for 28 cancers in Canada by age and birth cohort from 1983 to 2012. METHODS: Canadian incidence data for 20 to 84 year-olds were obtained from the Cancer Incidence in Five Continents Plus database. Age-period-cohort modeling was used to estimate the average annual percentage changes (AAPCs) and incidence rate ratios (IRRs) for 10-year birth cohorts (reference cohort, 1943) for 28 cancer types. RESULTS: Incidence increased for 13 cancer sites among adults younger than 50 years (1983-2012), with the largest increase occurring for rectal cancer (

xamination of historical data in Canada suggests that overall age-standardized incidence rates of cancer have decreased in males, but have increased in females. 1 Among both males and females between 1992 and 2013, the annual percent change (APC) in age-standardized incidence rates varied considerably among cancer sites, with the largest proportional increases seen in thyroid and liver cancers, and the largest decreases seen in stomach and laryngeal cancers. 1 However, analysis of age-standardized overall cancer rates may mask important epidemiologic trends for a given cancer site. For example, while overall rates of colorectal cancer are decreasing in Canada, we have previously shown that incidence is increasing substantially among adults younger than 50 years of age. 2 This discrepancy highlights the importance of examining the long-term trends in age-standardized incidence by individual cancer sites, which may be missed in overall trends. Age-standardized trends may provide insights that are of clinical or epidemiologic value, such as how previous primaryand secondary-prevention interventions affected the health of a population. Analysis by birth cohort can also help to inform hypotheses about potential early-life risk factors that have changed over generations. Finally, understanding cancerincidence trends specific to age and birth cohort can help guide future health-resource planning, as they may suggest health care needs of subpopulations. Although trends in cancer incidence have been well characterized in Canada for all ages combined, age-and birth cohort-specific trends have not been investigated for most cancer sites. In this study, we examined age-and birth cohort-specific incidence trends in Canada between 1971 and 2015 for 16 major cancer sites and all cancers combined.

We systematically reviewed and synthesized evidence on the impact of physical activity/exercise on cancer treatment efficacy. We included six preclinical and seven clinical studies. Exercise significantly enhanced the efficacy of chemotherapy and tamoxifen in seven of eight rodent models in either an additive, sensitizing, or synergistic manner. In clinical studies, preliminary evidence indicates that exercise during neoadjuvant, primary, and adjuvant treatment may enhance efficacy of cancer therapies; however, no clinical study was designed for this purpose.Here we discuss the biological mechanisms of exercise-associated enhancement of therapeutic efficacy and propose future research directions to definitively examine the effects of exercise on cancer treatment and patient outcomes.

There is epidemiologic and biologic evidence for a role of stress in breast cancer etiology and physical activity mitigates the negative effects of stress. We examined the potential for a dose-response relationship between two volumes of aerobic exercise and biomarkers of chronic stress in post-menopausal women. The Breast Cancer and Exercise Trial in Alberta is a randomized controlled trial with post-menopausal women randomized to either a MODERATE (150 min per week) or HIGH (300 min per week) volume of exercise over a one year intervention period. Fasting serum concentrations of cortisol, cortisone, corticosterone and 11-deoxycortisol at baseline, 12 months (the end of the intervention), and 24 months. Intention-to-treat analyses were performed using general linear models, adjusted for baseline biomarker concentrations. There were modest but non-statistically significant decreases in cortisol (HIGH: −4%, 95% CI: −7%, 2%; MODERATE: −1%, 95%: CI: −14%, 4%) and corticosterone (HIGH: −4%, 95% CI: −12%, 6%; MODERATE: −5%, 95% CI: −14%, 4%) concentrations for both exercise groups between baseline and 12 months, and no difference in cortisone concentrations. Intention-to-treat analysis of 386 (97%) participants showed no statistically significant group differences for changes in biomarker levels at 12 months. Between baseline and 12 months, there were no differences in cortisol or cortisone and, at 24 months all stress hormone levels increased to near-baseline levels with no significant differences between the two intervention groups.

Background Factors that are prognostic of early discontinuation of adjuvant chemotherapy among stage III colon cancer patients have yet to be described. To address this gap, a survey of medical oncologists and a systematic review and meta‐analysis were conducted. Methods A survey was distributed in March 2019 to medical oncologists who treat colon cancer within Alberta, Canada. Clinicians were asked to rank the prognostic importance of a set of variables using a Likert scale and agreement was quantified using a weighted Cohen's kappa. In addition, we systematically searched four databases up to July 2019. Meta‐analyses were conducted using a random‐effects model. Results Of the 25 clinicians who were sent the survey, 14 responded. Overall, there was no agreement regarding which variables were prognostic of early discontinuation (weighted Cohen's kappa = 0.12; 95% CI = 0.05‐0.18). From an initial 3927 articles, 18 investigations were identified for inclusion in our review. Based upon evidence from both the survey and the systematic review, the following four variables were identified as being prognostic of early discontinuation: (a) comorbidity (OR2+ vs 0 = 1.53; 95% CI = 1.30‐1.79); (b) performance status (ORECOG 2+ vs 0‐1 = 1.33; 95%CI = 1.07‐1.65); (c) T stage (ORT4 vs T1‐2 = 1.57; 95% CI = 0.99‐2.50); and (d) chemotherapy regimen (estimates not pooled due to heterogeneity). In addition to these factors, there was some suggestion that age, marital status/social support, muscle mass, N stage, and tumor grade had prognostic value. Conclusions Current evidence is heterogeneous and limited. Additional research is needed to confirm our findings and to explore additional prognostic factors.

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