Circadian rhythm disrupting behaviours and cancer outcomes in breast cancer survivors: A systematic review

PURPOSE: Circadian rhythm disruptors (e.g., night-shift work) are risk factors for breast cancer, however studies on their association with prognosis is limited. A small but growing body of research suggests that altered sleep patterns and eating behaviours are potential mechanistic links between circadian rhythm disruptors and breast cancer. We therefore systematically summarised literature examining the influence of circadian rhythm disrupting behaviours on cancer outcomes in women with breast cancer. METHODS: A systematic search of five databases from inception to January 2021 was conducted. Original research published in English, assessing the relationship between post-diagnosis sleep patters and eating behaviours, and breast cancer outcomes were considered. Risk of bias was assessed using the Newcastle-Ottawa Assessment Scale for Cohort Studies. RESULTS: Eight studies published original evidence addressing sleep duration and/or quality (k = 7) and, eating time and frequency (k = 1). Longer sleep duration (≥ 9 h versus [referent range] 6-8 h) was consistently associated with increased risk of all outcomes of interest (HR range: 1.37-2.33). There was limited evidence to suggest that measures of better sleep quality are associated with lower risk of all-cause mortality (HR range: 0.29-0.97). Shorter nightly fasting duration (\u3c 13 h versus ≥ 13 h) was associated with higher risk of all breast cancer outcomes (HR range: 1.21-1.36). CONCLUSION: Our review suggests that circadian rhythm disrupting behaviours may influence cancer outcomes in women with breast cancer. While causality remains unclear, to further understand these associations future research directions have been identified. Additional well-designed studies, examining other exposures (e.g., light exposure, temporal eating patterns), biomarkers, and patient-reported outcomes, in diverse populations (e.g., breast cancer subtype-specific, socio-demographic diversity) are warranted

Weight Loss and Mortality in Overweight and Obese Cancer Survivors: A Systematic Review

Background Excess adiposity is a risk factor for poorer cancer survival, but there is uncertainty over whether losing weight reduces the risk. We conducted a critical review of the literature examining weight loss and mortality in overweight or obese cancer survivors. Methods We systematically searched PubMed and EMBASE for articles reporting associations between weight loss and mortality (cancer-specific or all-cause) in overweight/obese patients with obesity-related cancers. Where available, data from the same studies on non-overweight patients were compared. Results Five articles describing observational studies in breast cancer survivors were included. Four studies reported a positive association between weight loss and mortality in overweight/obese survivors, and the remaining study observed no significant association. Results were similar for non-overweight survivors. Quality assessment indicated high risk of bias across studies. Conclusions There is currently a lack of observational evidence that weight loss improves survival for overweight and obese cancer survivors. However, the potential for bias in these studies is considerable and the results likely reflect the consequences of disease-related rather than intentional weight loss. There is a need for stronger study designs, incorporating measures of intentionality of weight loss, and extended to other cancers

Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis

IntroductionObesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification.MethodsWe performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003–02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype.ResultsMultivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype.ConclusionsSeverely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes

Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients

Abstract Background Postmenopausal obesity is associated with increased circulating levels of androgens and estrogens and elevated breast cancer risk. Crown-like structures (CLS; microscopic foci of dying adipocytes surrounded by macrophages) are proposed to represent sites of increased aromatization of androgens to estrogens. Accordingly, we examined relationships between CLS and sex-steroid hormones in breast adipose tissue and serum from postmenopausal breast cancer patients. Methods Formalin-fixed paraffin embedded benign breast tissues collected for research from postmenopausal women ( n \u2009=\u200983) diagnosed with invasive breast cancer in the Polish Breast Cancer Study (PBCS) were evaluated. Tissues were immunohistochemically stained for CD68 to determine the presence of CLS per unit area of adipose tissue. Relationships were assessed between CD68 density and CLS and previously reported sex-steroid hormones quantified using radioimmunoassays in serum taken at the time of diagnosis and in fresh frozen adipose tissue taken at the time of surgery. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relationships between hormones (in tertiles) and CLS. Results CLS were observed in 36% of benign breast tissues, with a higher frequency among obese versus lean women (54% versus 17%, p \u2009=\u20090.03). Detection of CLS was not related to individual hormone levels or breast tumor pathology characteristics. However, detection of CLS was associated with hormone ratios. Compared with women in the highest tertile of estrone:androstenedione ratio in fat, those in the lowest tertile were less likely to have CLS (OR 0.12, 95% CI 0.03\u20130.59). A similar pattern was observed with estradiol:testosterone ratio in serum and CLS (lowest versus highest tertile, OR 0.18, 95% CI 0.04\u20130.72). Conclusions CLS were more frequently identified in the breast fat of obese women and were associated with increased ..

Obesity promotes the expansion of metastasis-initiating cells in breast cancer

Obesity is a strong predictor of poor prognosis in breast cancer, especially in postmenopausal women. In particular, tumors in obese patients tend to seed more distant metastases, although the biology behind this observation remains poorly understood.Methods: To elucidate the effects of the obese microenvironment on metastatic spread, we ovariectomized C57BL/6 J female mice and fed them either a regular diet (RD) or a high-fat diet (HFD) to generate a postmenopausal diet-induced obesity model. We then studied tumor progression to metastasis of Py230 and EO771 grafts. We analyzed and phenotyped the RD and HFD tumors and the surrounding adipose tissue by flow cytometry, qPCR, immunohistochemistry (IHC) and western blot. The influence of the microenvironment on tumor cells was assessed by performing cross-transplantation of RD and HFD tumor cells into other RD and HFD mice. The results were analyzed using the unpaired Student t test when comparing two variables, otherwise we used one-way or two-way analysis of variance. The relationship between two variables was calculated using correlation coefficients.Results: Our results show that tumors in obese mice grow faster, are also less vascularized, more hypoxic, of higher grade and enriched in CD11b+Ly6G+ neutrophils. Collectively, this favors induction of the epithelial-to-mesenchymal transition and progression to claudin-low breast cancer, a subtype of triple-negative breast cancer that is enriched in cancer stem cells. Interestingly, transplanting HFD- derived tumor cells in RD mice transfers enhanced tumor growth and lung metastasis formation.Conclusions: These data indicate that a pro-metastatic effect of obesity is acquired by the tumor cells in the primary tumor independently of the microenvironment of the secondary site