Prediagnostic Physical Activity Research Articles

WHO-recommended levels of physical activity in relation to mammographic breast density, mammographic tumor appearance, and mode of detection of breast cancer

BackgroundDespite known benefits of physical activity in reducing breast cancer risk, its impact on mammographic characteristics remain unclear and understudied. This study aimed to investigate associations between pre-diagnostic physical activity and mammographic features at breast cancer diagnosis, specifically mammographic breast density (MBD) and mammographic tumor appearance (MA), as well as mode of cancer detection (MoD).MethodsPhysical activity levels from study baseline (1991–1996) and mammographic information from the time of invasive breast cancer diagnosis (1991–2014) of 1116 women enrolled in the Malmö Diet and Cancer Study cohort were used. Duration and intensity of physical activity were assessed according to metabolic equivalent of task hours (MET-h) per week, or World Health Organization (WHO) guideline recommendations. MBD was dichotomized into low-moderate or high, MA into spiculated or non-spiculated tumors, and MoD into clinical or screening detection. Associations were investigated through logistic regression analyses providing odds ratios (OR) with 95% confidence intervals (CI) in crude and multivariable-adjusted models.ResultsIn total, 32% of participants had high MBD at diagnosis, 37% had non-spiculated MA and 50% had clinical MoD. Overall, no association between physical activity and MBD was found with increasing MET-h/week or when comparing women who exceeded WHO guidelines to those subceeding recommendations (ORadj 1.24, 95% CI 0.78–1.98). Likewise, no differences in MA or MoD were observed across categories of physical activity.ConclusionsNo associations were observed between pre-diagnostic physical activity and MBD, MA, or MoD at breast cancer diagnosis. While physical activity is an established breast cancer prevention strategy, it does not appear to modify mammographic characteristics or screening detection.

Associations between Pre-Diagnostic Physical Activity with Breast Cancer Characteristics and Survival.

Simple SummaryPhysical activity is known to reduce breast cancer risk and improve patient prognosis. However, the association between pre-diagnostic physical activity and the aggressiveness of breast cancer is unclear. Here, we assessed the effects of pre-diagnostic physical activity on breast cancer aggressiveness among breast cancer patients. Despite not improving overall survival, higher levels of pre-diagnostic physical activity contributed to less aggressive forms of breast tumours. These results underline the importance of physical activity in improving patient prognosis. Physical activity (PA) is known to reduce breast cancer (BC) risk and improve patient prognosis. However, the association between pre-diagnostic PA and the aggressiveness of BC is unclear. We investigated the associations between PA, BC tumour characteristics, and survival. This retrospective observational study included 7688 BC patients from the Singapore Breast Cancer Cohort (2010–2016). PA information from the questionnaire included intensity (light/moderate/vigorous) and duration (<1 h/1–2 h/>2 h per week). A PA score (1–5) incorporating intensity and duration was calculated. Associations between PA score and tumour characteristics such as stage, histological grade, nodal and hormone receptor status were examined using multinomial regression. Moreover, 10-year overall survival was estimated using Cox regression analysis in 6572 patients after excluding patients with invalid survival data and stage IV disease. Breast tumours associated with higher PA score were more likely to be non-invasive (ORinvasive vs. non-invasive(reference) [95% CI]: 0.71 [0.58–0.87], p-trend = 0.001), of lower grade (ORpoorly vs. well differentiated(reference): 0.69 [0.52–0.93], p = 0.014), ER-positive (ORER-negative vs. ER-positive(reference): 0.94 [0.89–1.00], p-trend = 0.049), PR-positive (ORPR-negative vs. PR-positive(reference): 0.82 [0.67–0.99], p = 0.041), HER2-negative (ORHER2-negative vs. HER2-positive(reference): 1.29 [1.02–1.62], p-trend = 0.002), and less likely to be of HER2-overexpressed subtype (ORHER2-overexpressed vs. Luminal A(reference): 0.89 [0.81–0.98], p-trend = 0.018). These associations (odds ratios) were more pronounced among post-menopausal patients. A higher PA score did not improve survival. Higher levels of pre-diagnostic PA were associated with less aggressive tumours in BC patients. This illustrated another benefit of PA in addition to its known role in BC risk reduction.

Density of CD3+ and CD8+ Cells in the Microenvironment of Colorectal Cancer according to Prediagnostic Physical Activity.

Physical activity is associated not only with a decreased risk of developing colorectal cancer but also with improved survival. One putative mechanism is the infiltration of immune cells in the tumor microenvironment. Experimental findings suggest that physical activity may mobilize immune cells to the tumor. We hypothesized that higher levels of physical activity prior to colorectal cancer diagnosis are associated with higher densities of tumor-infiltrating T-lymphocytes in colorectal cancer patients. The study setting was a northern Swedish population-based cohort, including 109,792 participants with prospectively collected health- and lifestyle-related data. For 592 participants who later developed colorectal cancer, archival tumor tissue samples were used to assess the density of CD3+ and CD8+ cytotoxic T cells by IHC. Odds ratios for associations between self-reported, prediagnostic recreational physical activity and immune cell infiltration were estimated by ordinal logistic regression. Recreational physical activity >3 times per week was associated with a higher density of CD8+ T cells in the tumor front and center compared with participants reporting no recreational physical activity. Odds ratios were 2.77 (95% CI, 1.21-6.35) and 2.85 (95% CI, 1.28-6.33) for the tumor front and center, respectively, after adjustment for sex, age at diagnosis, and tumor stage. The risk estimates were consistent after additional adjustment for several potential confounders. For CD3, no clear associations were found. Physical activity may promote the infiltration of CD8+ immune cells in the tumor microenvironment of colorectal cancer. The study provides some evidence on how physical activity may alter the prognosis in colorectal cancer.

Abstract B045: Gene expression pathways associated with vigorous physical activity in prostate cancer

Abstract Background: Epidemiologic studies have consistently shown that men engaged in high levels of physical activity have lower risks of advanced and fatal prostate cancer. The mechanisms underlying this association are not well understood but may include changes in hormonal and anti-inflammatory pathways. Our objective was to investigate the link between prediagnostic physical activity and gene expression alterations in prostate tumor and adjacent normal tissue. Methods: We performed whole-gene expression profiling on tumor (N=248) and adjacent normal tissue (N=117) among a subset of men diagnosed with indolent and lethal prostate cancer between 1986 and 2005 in the prospective Health Professionals Follow-up Study. Men were followed prospectively for prostate cancer outcomes through 2011. Physical activity was ascertained by self-report of the average number of hours per week spent engaged in various forms of recreational physical activity at baseline and every two years thereafter. We examined cumulative average physical activity of vigorous intensity in units of metabolic equivalent of task (MET)-hours/week updated from baseline to the time prostate cancer diagnosis. Gene set enrichment analysis was performed among KEGG and hallmark gene sets to identify pathways with differential expression by vigorous activity. Results: We identified 33 KEGG and four Hallmark gene sets enriched in the adjacent normal tissue comparing men in the highest compared to the lowest quintile of vigorous activity (false-discovery rate &amp;lt; 0.25). Among the significant gene sets identified were cancer-related pathways as well as vascular smooth muscle contraction, angiogenesis, and insulin-signaling pathways. No gene sets were significantly enriched in the tumor tissue. Conclusions: These findings suggest that physical activity may influence prostate cancer development through epigenetic alterations in the prostate tissue. Future studies are needed to confirm these findings and further investigate potential mechanisms linking physical activity to risk of lethal prostate cancer. Citation Format: Claire H. Pernar, Giovanni Parmigiani, Edward L. Giovannucci, Eric B. Rimm, Stephen Finn, Michelangelo Fiorentino, Ericka M. Ebot, Lorelei A. Mucci. Gene expression pathways associated with vigorous physical activity in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B045.

Abstract 5254: The associations of habitual physical inactivity with cancer outcomes: Evidence from the Roswell Park Cancer Institute Data Bank and BioRepository

Abstract Despite recent position statements asserting that a physically active lifestyle reduces cancer mortality, inverse associations of physical activity (PA) with cancer outcomes are only well established for breast, colorectal, and prostate cancers. Further, the independent associations of physical inactivity with cancer outcomes are rarely reported. Given the prevalence of physical inactivity at the population level and among cancer survivors, we examined the associations of habitual physical inactivity with clinical outcomes in a large patient cohort at Roswell Park Cancer Institute (RPCI). We utilized data from 7,827 patients enrolled in the Data Bank and BioRepository (DBBR) at RPCI between 2003 and 2016. Pre-diagnostic PA, spanning the decade prior to diagnosis, and post-diagnostic PA, representing PA at study enrollment, were assessed by self-administered questionnaire. Patients reporting no regular PA in the decade prior to diagnosis (i.e., walking for exercise, moderate or vigorous PA, or weight training) and no PA after diagnosis were categorized as habitually inactive, our primary analytic exposure of interest. Multivariable Cox proportional hazards models adjusted for age, sex, stage, and tumor site were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) representing associations of habitual inactivity with all-cause mortality, cancer mortality, and disease recurrence. Additional variables (e.g., race, education, smoking, BMI, diabetes, tumor grade, treatment, occupational PA, etc.) were assessed for confounding utilizing the 10% change-in-estimate method. During the follow-up period, median time to follow-up was 54 months and 2,504 (32%) patients died. Collectively, 1,372 patients (17.5%) self-reported habitual inactivity. In comparison to patients who engaged in regular PA before and after diagnosis, habitually inactive patients experienced increased hazards of all-cause mortality (HR=1.41, 95% CI: 1.27-1.56, p&amp;lt;0.001), cancer mortality (HR=1.34, 95% CI: 1.19-1.52, p&amp;lt;0.001) and cancer recurrence (HR=1.15, 95% CI: 1.05-1.26, p=0.004). Associations remained robust and consistent in subgroup analyses by sex, stage and BMI. In sensitivity analyses, associations were strengthened when excluding patients with &amp;lt;3 years of follow-up and remained significant when excluding breast, colorectal and prostate cancer patients for all-cause mortality (HR=1.33, 95% CI: 1.18-1.50, p&amp;lt;0.001), cancer-specific mortality (HR=1.32, 95% CI: 1.14-1.52, p&amp;lt;0.001) and disease recurrence (HR =1.17, 95% CI: 1.04-1.30, p=0.007). We observed consistent evidence that habitual inactivity associates with increased hazards of cancer recurrence and mortality across multiple tumor types. Well-designed survivorship studies are needed to confirm how much mortality can be reduced among regularly active cancer patients. Citation Format: Rikki A. Cannioto, Shruti Dighe, Karen Hulme, Alexandra Drake, Susan E. McCann, Christine B. Ambrosone. The associations of habitual physical inactivity with cancer outcomes: Evidence from the Roswell Park Cancer Institute Data Bank and BioRepository [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5254.

Physical activity and survival of colorectal cancer patients: Population-based study from Germany.

Increasing evidence shows physical activity to be associated with improved colorectal cancer (CRC) prognosis. However, large-scale prospective patient cohorts, comprehensively ascertaining physical activity, comprehensively considering potential variation by CRC stage and considering specific outcome measures, are sparse. Therefore, we aimed to evaluate the association of lifetime and latest prediagnostic leisure time physical activity with relevant prognostic outcomes in a large population-based cohort of CRC patients. 3,121 patients, diagnosed with CRC in 2003-2010 (median age: 69 years), were interviewed on sociodemographic and lifestyle factors, medication and comorbidities. Cancer recurrence, vital status and cause of death were documented over a median follow-up time of 4.8 years. Associations between lifetime and latest prediagnostic leisure time physical activity and overall, CRC-specific, recurrence-free and disease-free survival were evaluated with Cox regression. Latest but not lifetime leisure time physical activity [in metabolic task hours per week (MET-h/wk)] was associated with decreased overall and CRC-specific mortality (>56.2 vs. ≤13.2 MET-h/wk: adjusted hazard ratio (aHR)Overall/latest = 0.75; 95% confidence interval (CI) = 0.61-0.91; aHRCRC-specific/latest = 0.81; 95% CI = 0.64-1.02). In particular lifetime and latest walking were associated with decreased mortality (>20 vs. 0-10 MET-h/wk of walking: aHROverall/latest = 0.66; 95% CI = 0.56-0.77; aHRCRC-specific/latest = 0.72; 95% CI = 0.60-0.87; aHROverall/lifetime = 0.78; 95% CI = 0.66-0.93; aHRCRC-specific/lifetime = 0.71; 95% CI = 0.58-0.86). Associations were particularly pronounced for lifetime walking in metastatic (stage IV) and for latest walking in nonmetastatic disease patients. Prediagnostic physical activity was associated with improved CRC prognosis. Associations might be restricted to certain activities or depend on (non)metastatic disease state. Further optimization of activity recommendations and increase of recommendation adherence may help to improve patients' prognosis.

Prediagnostic Physical Activity and Colorectal Cancer Survival: Overall and Stratified by Tumor Characteristics

Physical activity is associated with a lower incidence of colorectal cancer; however, the relationship of physical activity with colorectal cancer survival is not yet clear. We evaluated the association between prediagnostic physical activity and colorectal cancer survival, overall and accounting for tumor markers associated with colorectal cancer survival: BRAF and KRAS mutation status and microsatellite instability (MSI) status. Participants were 20- to 74-year-old colorectal cancer patients diagnosed between 1998 and 2007 from the population-based Seattle Colon Cancer Family Registry (S-CCFR). Self-reported physical activity in the years preceding colorectal cancer diagnosis was summarized as average metabolic equivalent task hours per week (MET-h/wk; n = 1,309). Somatic BRAF and KRAS mutations and MSI status were evaluated on a subset of patients (n = 1043). Cox regression was used to estimate HRs and 95% confidence intervals (CI) for overall and disease-specific survival after adjusting for relevant confounders. Stratified analyses were conducted across categories of BRAF, KRAS, and MSI, as well as tumor stage and site. Higher prediagnostic recreational physical activity was associated with significantly more favorable overall survival (HR for highest vs. lowest category, 0.70; 95% CI, 0.52-0.96); associations were similar for colorectal cancer-specific survival. Results consistently indicated a favorable association with physical activity across strata defined by tumor characteristics. Individuals who were physically active before colorectal cancer diagnosis experienced better survival than those who were inactive or minimally active. Our results support existing physical activity recommendations for colorectal cancer patients and suggest that the beneficial effect of activity is not specific to a particular molecular phenotype of colorectal cancer.

Abstract 2172: Physical activity in relation to overall and colorectal cancer specific survival in the Seattle Colon Cancer Family Registry

Abstract Background Previous studies have suggested that physical activity is associated with a reduced risk of colon cancer. The association of physical activity with colorectal cancer (CRC) survival, however, is less clear. Studies evaluating the association between post-diagnostic physical activity and CRC survival suggest a favorable survival among those who engage in regular physical activity after diagnosis. However, such studies are limited by the possibility of reverse causality since individuals engaging in regular physical activity after diagnosis may have had a better prognosis to begin with. Methods We evaluated the association between pre-diagnostic physical activity and survival, both overall and CRC-specific, within the Seattle Colon Cancer Family Registry (SCCFR), a prospective cohort of persons diagnosed with CRC between 1997 and 2002. All cases completed a risk-factor questionnaire including information on medical history, demographic and lifestyle factors, such as obesity and decade-specific recreational physical activity. Vital status and cause of death was determined through linkage to a regional cancer registry and National Death Index. Tumor markers (BRAF and KRAS mutation status) were evaluated for a subset of cases. Physical activity was summarized as average weekly metabolic equivalent-task hours (MET-h/week). Adjusted hazard ratios (HR) and 95% confidence limits (95%CI) were estimated using Cox regression. Results Primary analyses included 1171 persons who self-reported their physical activity status, of whom 471 died (292 deaths attributable to CRC; median follow-up 6.3 years). After adjusting for age at diagnosis, sex, body mass index and smoking status, those who engaged in physical activity had a significantly lower risk of dying from any cause compared to those who did not engage in any physical activity (HR 0.72, 95%CI 0.51-0.99; HR 0.62, 95%CI 0.44-0.87; and HR 0.60, 95%CI 0.43-0.85 for &amp;gt;0-6.4, 6.4-19.2, and &amp;gt;19.2 MET-h/wk, respectively; P for trend=0.035). Results for CRC-specific survival were similar and suggested improved survival among physically active individuals compared to those that were inactive, although no trend was evident (HR 0.81, 95%CI 0.51-1.28; HR 0.72, 95%CI 0.45-1.15; and HR 0.72, 95% CI 0.44-1.14 for &amp;gt;0-6.4, 6.4-19.2, &amp;gt;19.2 MET-h/wk respectively; P for trend= 0.52). Further adjustment for stage at diagnosis or BRAF and KRAS mutation status did not alter the results. Conclusion Our results suggest that individuals who are physically active prior to CRC diagnosis experience more favorable survival than those who are inactive. Increased physical activity was also associated with better CRC-specific survival, but this trend was not statistically significant. Continued follow-up of this and other larger cohorts is needed to further clarify the role of physical activity in CRC prognosis. Citation Format: Sheetal S. Hardikar, Polly A. Newcomb, Michael N. Passarelli, Peter T. Campbell, Amanda I. Phipps. Physical activity in relation to overall and colorectal cancer specific survival in the Seattle Colon Cancer Family Registry. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2172. doi:10.1158/1538-7445.AM2014-2172

Association of prediagnostic physical activity with survival following breast cancer diagnosis: influence of TP53 mutation status

Physical activity both before and after breast cancer diagnosis has been associated with improved survival. However, it is not clear whether this association differs by molecular features of the tumor or by recency of the physical activity to the time of diagnosis. We examined the association of prediagnostic physical activity with survival in a cohort of 1,170 women with primary, incident, and histologically confirmed breast cancer, examining tumor molecular subtypes. Cox regression models were used to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI). Mean follow-up time was 87.4 months after breast cancer diagnosis; there were 170 deaths identified. Compared with inactive patients (<3 h/week), women with higher average lifetime physical activity (>6 h/week) had reduced risk of all-cause mortality (adjusted HR = 0.61, 95 % CI 0.40-0.95; p trend =0.04). There were no clear differences in the associations for lifetime and more recent physical activity. Lifetime physical activity was also weakly associated with decreased risk of breast cancer-specific mortality. Higher lifetime physical activity was associated with reduced risk of all-cause mortality among women with ER-positive tumors (HR = 0.52, 95 % CI 0.29-0.93) and mutant TP53 tumors (HR = 0.22, 95 % CI 0.06-0.72); however, no statistically significant interactions were observed for ER or TP53 status. Our study further supports that prediagnostic physical activity improves overall survival following breast cancer and suggests that the associations of prediagnostic physical activity with survival following breast cancer may vary by molecular features of the tumor, particularly ER and TP53 status.

Higher levels of physical activity significantly increase survival in women with colorectal cancer

Higher levels of physical activity significantly increase survival in women with colorectal cancer