Background There is a paucity of information on the prevalence of dietary supplement use in breast cancer survivors. Only a few studies have examined the impact of dietary supplements, particularly antioxidants, on breast cancer prognosis and the results are inconclusive. Objective We examined pre- and postdiagnosis use of supplements in postmenopausal breast cancer survivors in Germany and investigated associations between postdiagnosis use of antioxidants and other supplements, and prognosis (total and breast cancer mortality, and recurrence-free survival) both overall and in women who received chemotherapy and radiation therapy. Design Data from 2223 postmenopausal women diagnosed with nonmetastatic breast cancer from the population-based Mamma Carcinoma Risk Factor Investigation (MARIE) study were used. Women were interviewed at recruitment in 2002–2005 and again in 2009 and followed-up until 30 June 2015. Multivariate Cox regression analysis was used to estimate HRs and corresponding 95% CIs. Results Pre- and postdiagnosis supplement use was reported by 36% and 45% of the women, respectively. There were 240 deaths (134 from breast cancer) and 200 breast cancer recurrences after a median follow-up time of 6.0 y after the 2009 re-interview. After adjusting for relevant confounders, concurrent antioxidant use with chemotherapy or radiation therapy among 1940 women was associated with increased risk of total mortality (HR: 1.64; 95% CI: 1.01, 2.66) and worsened recurrence-free survival (HR: 1.84; 95% CI: 1.26, 2.68). Overall postdiagnosis supplement use was not associated with breast cancer prognosis. Conclusions Antioxidant use during chemotherapy or radiation therapy was associated with worsened breast cancer prognosis in postmenopausal women. There was no overall association between postdiagnosis supplement use and breast cancer prognosis. Results from our study align with the current recommendation to possibly avoid the use of antioxidants during chemotherapy or radiation therapy.

Higher lignan exposure has been associated with lower all-cause mortality (ACM) and breast cancer-specific mortality (BCSM) for postmenopausal breast cancer patients. However, the biological mechanisms underpinning these associations are still unclear. We investigated for the first time whether and to what extent the association between enterolactone (ENL), the major lignan metabolite, and postmenopausal breast cancer prognosis is mediated by inflammatory biomarkers. Circulating concentrations of ENL and inflammatory markers were measured in a population-based prospective cohort of 1,743 breast cancer patients recruited between 2002 and 2005 and followed-up until 2009. Hazard ratios (HR) and 95% CIs were estimated using multivariable Cox regression. Mediation analysis was performed to estimate the percentage association between ENL (log2) and ACM, BCSM and distant disease-free survival (DDFS), which is mediated by C-reactive protein (CRP) (log2), as the strongest potential mediator, and also interleukin (IL)-10. Median serum/plasma ENL and CRP concentrations for all patients, including 180 deceased patients, were 23.2 and 17.5 nmol/L, and 3.2 and 6.5 mg/l, respectively. ENL concentrations were significantly inversely associated with ACM, BCSM and DDFS (per doubling of ENL concentrations: HRs 0.93 [0.87, 0.99], 0.91 [0.84, 0.99] and 0.92 [0.87, 0.99]), after adjusting for prognostic factors and BMI. Estimated 18, 14 and 12% of the effects of ENL on ACM, BCSM and DDFS, respectively, were mediated through CRP. No mediational effect of IL-10 was found. We provide first evidence that the proinflammatory marker CRP may partially mediate the association of ENL with postmenopausal breast cancer survival, which supports hormone-independent mechanisms.

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.