Circulating enterolactone concentrations and prognosis of postmenopausal breast cancer: assessment of mediation by inflammatory markers

Jaskulski, Stefanie; Jung, Audrey; Behrens, Sabine; Johnson, Theron; Kaaks, Rudolf; Thöne, Kathrin; Flesch-Janys, Dieter; Sookthai, Disorn; Chang‐Claude, Jenny

doi:10.1002/ijc.31647

Cited by 18 publications

(18 citation statements)

References 48 publications

(92 reference statements)

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“…Therefore, non-detectable values for IL-6 were set to missing, while non-detectable values for the remaining inflammatory markers were set to half the detection limit due to highly skewed distributions [ 24 ]. Missing values above fit curve range as well as extreme outliers were set to missing, resulting in available biomarker concentrations for between 2729 (e.g., IL-6) and 2761 patients (e.g., TNF-α) [ 25 ] ( Supplementary Tables 1A and 1B ).…”

Section: Methodsmentioning

confidence: 99%

Tired of feeling tired – The role of circulating inflammatory biomarkers and long-term cancer related fatigue in breast cancer survivors

et al. 2021

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Background Low-grade inflammation has been associated with cancer related fatigue (CRF). However, most studies focused on CRF during or shortly after treatment. Longitudinal studies are rare with inconsistent results. We assessed the association of inflammatory biomarkers with total CRF and all subdomains (physical, cognitive, affective) in long-term breast cancer survivors. Method Patients recruited between 2002 and 2005 provided information on CRF at first follow-up (FU1) (N = 1292) and second follow-up (FU2) (N = 1205), after a median of 6.2 years and 11.7 years, respectively. Associations of 11 inflammatory biomarkers with CRF at FU1 and at FU2 were assessed using linear regression models. Logistic regression models were used to compare patients fatigued at both time-points and those never fatigued (N = 932). Results C-reactive protein (CRP) was significantly associated with total CRF at FU1 (β = 1.47, 95%CI = 0.62–2.31, p = 0.0007), at FU2 (β = 1.98, 95 %CI = 0.96–2.99, p = 0.0001) and with persistent CRF (OR = 1.29, 95%CI = 1.13–1.47, p < 0.0001). IL-6 levels were associated with total CRF at FU1 (β = 1.01, 95%CI = 0.43–1.59, p = 0.0006), but not with CRF at FU2 or persistent CRF. No association remained significant after adjustment for relevant covariates. Discussion CRP and Il-6 were associated with risk of CRF in long-term breast cancer survivors, but were not independent of other known risk factors, suggesting that currently studied inflammatory markers are not suitable to identify patients at risk of long-term CRF.

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Section: Methodsmentioning

confidence: 99%

Tired of feeling tired – The role of circulating inflammatory biomarkers and long-term cancer related fatigue in breast cancer survivors

et al. 2021

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“…Interviews were conducted by trained interviewers using standard questionnaires person to person at recruitment and by telephone in 2009 at follow-up for postdiagnosis physical activity and other lifestyle, personal, and clinical characteristics. Information on vital status was collected from population registries in 2009 [10] and 2015.…”

Section: Methodsmentioning

confidence: 99%

Pre- to postdiagnosis leisure-time physical activity and prognosis in postmenopausal breast cancer survivors

et al. 2019

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BackgroundPhysical activity (PA) before and after breast cancer diagnosis has been reported to be associated with lower mortality. However, whether changes in the activity after diagnosis impact prognosis is unclear and has not received much attention. This study aimed to examine pre- to postdiagnosis leisure-time PA and breast cancer prognosis.MethodsWe used data from the MARIE study, a prospective population-based patient cohort study of 3813 postmenopausal breast cancer patients, aged 50–74 at diagnosis, recruited from 2002 to 2005, re-interviewed in 2009, and followed up until June 2015. Prediagnosis PA was assessed at recruitment; postdiagnosis PA was assessed at re-interview in 2009. To examine pre- to postdiagnosis change in PA, women were categorized by pre- and postdiagnosis PA using a cut-off of 7.5 MET-h/week for meeting PA recommendations and combined into four groups: insufficiently active, increasingly active, decreasingly active, and sufficiently active. Cox regression models with delayed entry were used to assess associations between pre- to postdiagnosis patterns of PA and overall mortality (OM), breast cancer mortality (BCM), and recurrence-free survival (RFS). Additional analyses of pre- and postdiagnosis PA (no activity (reference), low activity, sufficient activity) with cancer outcomes, such as using a time-dependent model, were performed. In total, 2042 patients were included in the analyses.ResultsThere were 206 deaths (114 from breast cancer) after a median follow-up time of 6.0 years after the 2009 interview. Compared to insufficiently active women, increasingly active women were at lower risk of OM, BCM, and RFS (HR (95%CI) of 0.50 (0.31–0.82), 0.54 (0.30–1.00), 0.58 (0.40–0.84), respectively). In sufficiently active women, associations for OM (0.75 (0.48–1.15)), BCM (0.61 (0.33–1.13)), and RFS 0.80 (0.57–1.14)) were similar to increasingly active women but attenuated, and decreasingly active women were not at lower risk for OM (0.91 (0.61–1.36)), BCM (0.80 (0.45–1.42)), and RFS (1.04 (0.76–1.43)). In time-dependent analyses, sufficient activity vs. no activity was associated with better OM (0.73 (0.57–0.93)), BCM (0.64 (0.46–0.89)), and RFS (0.82 (0.68–0.99)). Low activity was not significantly associated with prognosis.ConclusionOur data support benefits for breast cancer prognosis in being physically active pre- and postdiagnosis particularly for women who were insufficiently active prediagnosis.

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“…Recent research suggests that much of the effect of lignans may be as a result of antiinflammatory influences, which we have not as yet adequately explored in our clinical trial specimens [55][56][57]. Indeed, our companion study in an immunocompetent mouse model of triple negative breast cancer suggested that SDG, in doses producing equivalent enterolactone and enterodiol blood levels as in our human pilot study, suppressed NFκB activation [14].…”

Section: Discussionmentioning

confidence: 79%

Randomized Phase IIB Trial of the Lignan Secoisolariciresinol Diglucoside in Premenopausal Women at Increased Risk for Development of Breast Cancer

Fabian

Khan

Garber

et al. 2020

Cancer Prevention Research

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We conducted a multi-institutional, placebo-controlled Phase IIB trial of the lignan secoisolariciresinol diglucoside (SDG) found in flaxseed. Benign breast tissue was acquired by random periareolar fine needle aspiration (RPFNA) from pre-menopausal women at increased risk for breast cancer. Those with hyperplasia and ≥2% Ki-67 positive cells were eligible for randomization 2:1 to 50 mg SDG/day (Brevail®) vs placebo for 12 months with repeat biospecimen acquisition. The primary endpoint was difference in change in Ki-67 between randomization groups. 180 women were randomized, with 152 ultimately evaluable for the primary endpoint. Median baseline Ki-67 was 4.1% with no difference between arms. Median Ki-67 change was-1.8% in the SDG arm (P=0.001) and-1.2% for placebo (P=0.034); with no significant difference between arms. As menstrual cycle phase affects proliferation, secondary analysis was performed for 117 women who by progesterone levels were in the same phase of the menstrual cycle at baseline and off-study tissue sampling. The significant Ki-67 decrease persisted for SDG (median-2.2%; P=0.002) but not placebo (median-1.0%). RT-qPCR was performed on 77 pairs of tissue specimens. 22 had significant ERα gene expression changes (<0.5 or >2.0) with 7/10 increases in placebo and 10/12 decreases for SDG (P=0.028), and a difference between arms (P =0.017). Adverse event incidence was similar in both groups, with no evidence that 50 mg/day SDG is harmful. Although the proliferation biomarker analysis showed no difference between the treatment group and the placebo, the trial demonstrated use of SDG is tolerable and safe.

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Circulating enterolactone concentrations and prognosis of postmenopausal breast cancer: assessment of mediation by inflammatory markers

Cited by 18 publications

References 48 publications

Tired of feeling tired – The role of circulating inflammatory biomarkers and long-term cancer related fatigue in breast cancer survivors

Tired of feeling tired – The role of circulating inflammatory biomarkers and long-term cancer related fatigue in breast cancer survivors

Pre- to postdiagnosis leisure-time physical activity and prognosis in postmenopausal breast cancer survivors

Randomized Phase IIB Trial of the Lignan Secoisolariciresinol Diglucoside in Premenopausal Women at Increased Risk for Development of Breast Cancer

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