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Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment.

ABSTRACT: The prognosis of early breast cancer (BC) relies on cell autonomous and immune parameters. The impact of the intestinal microbiome on clinical outcome has not yet been evaluated. Shotgun metagenomics was used to determine the composition of the fecal microbiota in 121 specimens from 76 early BC patients, 45 of whom were paired before and after chemotherapy. These patients were enrolled in the CANTO prospective study designed to record the side effects associated with the clinical management of BC. We analyzed associations between baseline or post-chemotherapy fecal microbiota and plasma metabolomics with BC prognosis, as well as with therapy-induced side effects. We examined the clinical relevance of these findings in immunocompetent mice colonized with BC patient microbiota that were subsequently challenged with histo-compatible mouse BC and chemotherapy. We conclude that specific gut commensals that are overabundant in BC patients compared with healthy individuals negatively impact BC prognosis, are modulated by chemotherapy, and may influence weight gain and neurological side effects of BC therapies. These findings obtained in adjuvant and neoadjuvant settings warrant prospective validation.

SUBMITTER: Terrisse S

PROVIDER: S-EPMC8408230 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment.

Terrisse Safae S Derosa Lisa L Iebba Valerio V Ghiringhelli François F Vaz-Luis Ines I Kroemer Guido G Fidelle Marine M Christodoulidis Stergios S Segata Nicola N Thomas Andrew Maltez AM Martin Anne-Laure AL Sirven Aude A Everhard Sibille S Aprahamian Fanny F Nirmalathasan Nitharsshini N Aarnoutse Romy R Smidt Marjolein M Ziemons Janine J Caldas Carlos C Loibl Sibylle S Denkert Carsten C Durand Sylvere S Iglesias Claudia C Pietrantonio Filippo F Routy Bertrand B André Fabrice F Pasolli Edoardo E Delaloge Suzette S Zitvogel Laurence L

Cell death and differentiation 20210507 9

The prognosis of early breast cancer (BC) relies on cell autonomous and immune parameters. The impact of the intestinal microbiome on clinical outcome has not yet been evaluated. Shotgun metagenomics was used to determine the composition of the fecal microbiota in 121 specimens from 76 early BC patients, 45 of whom were paired before and after chemotherapy. These patients were enrolled in the CANTO prospective study designed to record the side effects associated with the clinical management of B ...[more]

PMID: 33963313

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Project description:BackgroundIdentifying and understanding modifiable factors for the well-being of cancer patients is critical in survivorship research. We studied variables associated with the exercise habits of breast cancer patients and investigated if the achievement of exercise recommendations was associated with enhanced quality of life and/or psychological well-being. Material and Methods. 311 women from Finland, Portugal, Israel, and Italy receiving adjuvant therapy for stage I-III breast cancer answered questions about sociodemographic factors and physical exercise. Quality of life was assessed by the EORTC C30 and BR23 questionnaires. Anxiety and depression were evaluated using the HADS scale.ResultsAt the beginning of adjuvant therapy and after twelve months, 32% and 26% of participants were physically inactive, 27% and 30% exercised between 30 and 150 minutes per week, while 41% and 45% exercised the recommended 150 minutes or more per week. Relative to other countries, Finnish participants were more likely to be active at baseline and at twelve months (89% vs. 50%, p < 0.001 and 87% vs. 64%, p < 0.001). Participants with stage I cancer were more likely to be active at twelve months than those with a higher stage (80% vs. 70%,p < 0.05). The inactive participants reported more anxiety (p < 0.05) and depression (p < 0.001), lower global quality of life (p < 0.001), and more side effects (p < 0.05) than the others at twelve months. Accordingly, those who remained inactive or decreased their level of exercise from baseline to twelve months reported more anxiety (p < 0.01) and depression (p < 0.001), lower global quality of life (p < 0.001), and more side effects (p < 0.05) than those with the same or increased level of exercise.ConclusionFor women with early breast cancer, exercise was associated with a better quality of life, less depression and anxiety, and fewer adverse events of adjuvant therapy. Trial registration number: NCT05095675. Paula Poikonen-Saksela on behalf of Bounce consortium (https://www.bounce-project.eu/).

Project description:BackgroundThe acquisition and development of infant gut microbiota can be influenced by numerous factors, of which early antibiotic treatment is an important one. However, studies on the effects of antibiotic treatment in early life on clinical outcomes and establishment and development of the gut microbiota of term infants are limited. Disturbed microbiota composition is hypothesized to be an underlying mechanism of an aberrant development of the immune system. This study aims to investigate the potential clinical and microbial consequences of empiric antibiotic use in early life.Methods/design450 term born infants, of whom 150 are exposed to antibiotic treatment in early life and 300 are not (control group), are included in this observational cohort study with a one-year follow-up. Clinical outcomes, including coughing, wheezing, fever >38 °C, runny nose, glue ear, rash, diarrhea and >3 crying hours a day, are recorded daily by parents and examined by previously defined doctor's diagnosis. A blood sample is taken at closure to investigate the infant's vaccination response and sensitization for food and inhalant allergens. Fecal samples are obtained at eight time points during the first year of life. Potential differences in microbial profiles of infants treated with antibiotics versus healthy controls will be determined by use of 16S-23S rRNA gene analysis (IS-pro). Microbiota composition will be described by means of abundance, diversity and (dis)similarity. Diversity is calculated using the Shannon index. Dissimilarities between samples are calculated as the cosine distance between each pair of samples and analyzed with principal coordinate analysis. Clinical variables and possible associations are assessed by appropriate statistics.DiscussionBoth clinical quantitative and qualitative microbial effects of antibiotic treatment in early life may be demonstrated. These findings can be important, since there is evidence that manipulation of the infant microbiota by using pre- or probiotics can restore the ecological balance of the microbiota and may mitigate potential negative effects on the developing immune system, when use of antibiotics cannot be avoided.Trial registrationClinicalTrials.gov NCT02536560. Registered 28 August 2015.

Project description:ImportanceIn observational studies, patients' treatment outcome expectations have been associated with better outcomes (ie, a placebo response), whereas concerns about adverse side effects have been associated with an in increase in the negative effects of treatments (ie, a nocebo response). Some randomized trials have suggested that communication from clinicians could affect the treatment outcomes by changing patients' expectations.ObjectiveTo investigate whether treatment outcome expectations and reported adverse side effects could be affected by different briefing contents before a minimal acupuncture treatment in patients with chronic low back pain (CLBP).Design, setting, and participantsThis randomized single-blinded clinical trial was conducted among patients with CLBP at 1 outpatient clinic in Switzerland who had a pain intensity of at least 4 on a numeric rating scale from 0 to 10. Different recruitment channels were used to enroll patients. Data were collected from May 2016 to December 2017 and were analyzed from June to November 2018.InterventionsPatients were randomized to receive either a regular expectation briefing or a high expectation briefing (effectiveness) and either a regular adverse side effect briefing or an intense adverse side effect briefing (adverse side effect) in a 2 × 2 factorial design. The intervention (briefing sessions and written materials) was standardized and delivered before the acupuncture treatment, with additional booster informative emails provided during the 4-week, 8-session acupuncture course.Main outcomes and measuresThe primary end point was the patients' expectations regarding the effectiveness of the acupuncture treatment (Expectation for Treatment Scale [ETS]) after the briefing and the subsequent pain intensity (numeric rating scale). The primary end point for the adverse side effect briefing was the adverse side effect score at the end of the acupuncture treatment, derived from session-by-session assessments of adverse side effects.ResultsA total of 152 patients with CLBP (mean [SD] age, 39.54 [12.52] years; 100 [65.8%] women) were included. The estimated group difference (regular vs high) for the ETS was -0.16 (95% CI -0.81 to 0.50, P = .64), indicating no evidence for a difference between intervention groups. There was also no evidence for a difference in pain intensity at the end of the acupuncture treatment between the groups with different expectation briefings. The adverse side effects score in the group with the intense adverse side effect briefing were estimated to be 1.31 times higher (95% CI, 0.94 to 1.82; P = .11) than after a regular adverse side effect briefing, but the finding was not statistically significant.Conclusions and relevanceIn this study, suggestions regarding treatment benefits (placebo) and adverse side effects (nocebo) did not affect treatment expectations or adverse side effects. Information regarding adverse side effects might require more research to understand nocebo responses.Trial registrationGerman Clinical Trials Register Identifier: DRKS00010191.

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Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment.

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Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment.

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