ABSTRACT
This clinical study explored the associations between the intestinal microbiota, chemotherapy toxicity, and treatment response in postmenopausal oestrogen receptor positive breast cancer patients.Oestrogen receptor positive postmenopausal breast cancer patients were prospectively enroled in a multicentre cohort study and treated with 4 cycles of (neo)adjuvant adriamycin, cyclophosphamide (AC) followed by 4 cycles of docetaxel (D). Patients collected a faecal sample and completed a questionnaire before treatment, during AC, during D, and after completing AC-D. Chemotherapy toxicity and tumour response were determined. Intestinal microbiota was analysed by amplicon sequencing of the 16 S rRNA V4 gene-region. In total, 44 patients, including 18 neoadjuvant patients, were included, and 153 faecal samples were collected before AC-D (n = 44), during AC (n = 43), during D (n = 29), and after AC-D treatment (n = 37), 28 participants provided all four samples. In the whole group, observed species richness reduced during treatment (p = 0.042). The abundance of Proteobacteria, unclassified Enterobacterales, Lactobacillus, Ruminococcaceae NK4A214 group, Marvinbryantia, Christensenellaceae R7 group, and Ruminococcaceae UCG-005 changed significantly over time. Patients with any grade diarrhoea during docetaxel treatment had a significantly lower observed species richness compared to patients without diarrhoea. In the small group neoadjuvant treated patients, pathologic response was unrelated to baseline intestinal microbiota richness, diversity and composition. While the baseline microbiota was not predictive for pathologic response in a rather small group of neoadjuvant treated patients in our study, subsequent shifts in microbial richness, as well as the abundance of specific bacterial taxa, were observed during AC-D treatment in the whole group and the neoadjuvant group.
ABSTRACT
BACKGROUND: Previous preclinical and clinical research has investigated the role of intestinal microbiota in carcinogenesis. Growing evidence exists that intestinal microbiota can influence breast cancer carcinogenesis. However, the role of intestinal microbiota in breast cancer needs to be further investigated. This study aimed to identify the microbiota differences between postmenopausal breast cancer patients and controls. PATIENTS AND METHODS: This prospective cohort study compared the intestinal microbiota richness, diversity, and composition in postmenopausal histologically proven ER+/HER2- breast cancer patients and postmenopausal controls. Patients scheduled for (neo)adjuvant adriamycin, cyclophosphamide (AC), and docetaxel (D), or endocrine therapy (tamoxifen) were prospectively enrolled in a multicentre cohort study in the Netherlands. Patients collected a faecal sample and completed a questionnaire before starting systemic cancer treatment. Controls, enrolled from the National Dutch Breast Cancer Screening Programme, also collected a faecal sample and completed a questionnaire. Intestinal microbiota was analysed by amplicon sequencing of the 16S rRNA V4 gene region. RESULTS: In total, 81 postmenopausal ER+/HER2- breast cancer patients and 67 postmenopausal controls were included, resulting in 148 faecal samples. Observed species richness, Shannon index, and overall microbial community structure were not significantly different between breast cancer patients and controls. There was a significant difference in overall microbial community structure between breast cancer patients scheduled for adjuvant treatment, neoadjuvant treatment, and controls at the phylum (p = 0.042) and genus levels (p = 0.015). Dialister (p = 0.001) and its corresponding family Veillonellaceae (p = 0.001) were higher in patients scheduled for adjuvant treatment, compared to patients scheduled for neoadjuvant treatment. Additional sensitivity analysis to correct for the potential confounding effect of prophylactic antibiotic use, indicated no differences in microbial community structure between patients scheduled for neoadjuvant systemic treatment, adjuvant systemic treatment, and controls at the phylum (p = 0.471) and genus levels (p = 0.124). CONCLUSIONS: Intestinal microbiota richness, diversity, and composition are not different between postmenopausal breast cancer patients and controls. The increased relative abundance of Dialister and Veillonellaceae was observed in breast cancer patients scheduled for adjuvant treatment, which might be caused by a relative decrease in other bacteria due to prophylactic antibiotic administration rather than an absolute increase.
ABSTRACT
BACKGROUND: Studies have shown that multidisciplinary team meetings (MDTM) improve diagnostic work-up and treatment-decisions. This study aims to evaluate the influence of implementing a regional-video-Upper-GI-MDTM (uMDTM) for oesophageal cancer (OC) on the number of patients discussed, treatment-decisions, perspectives of involved clinicians and overall survival (OS) in the Eindhoven Upper-GI Network consisting of 1 resection hospital and 5 referring hospitals. METHODS: Between 2012 and 2018, patients diagnosed with OC within this region, were selected from the Netherlands Cancer Registry(n = 1119). From 2014, an uMDTM was gradually implemented and a mixed-method quantitative and qualitative design was used to analyse changes. Quantitative outcomes were described before and after implementation of the uMDTM. Clinicians were interviewed to assess their perspectives regarding the uMDTM. RESULTS: After participation in the uMDTM more patients were discussed in an MDTM (80%-89%,p < 0.0001) and involvement of a resection centre during the uMDTM increased (43%-82%,p < 0.0001). The proportion of patients diagnosed with potentially curable OC (cT1-4a-x, any cN, cM0) remained stable (59%-61%, p = 0.452). Endoscopic or surgical resections were performed more often (28%-34%,p = 0.034) and the use of best supportive care decreased (21%-15%,p = 0.018). In the qualitative part an improved knowledge, collaboration and discussion was perceived due to implementation of the uMDTM. Three-year OS for all OC patients increased after the implementation of the uMDTM (24%-30%,p = 0.025). CONCLUSIONS: Implementation of a regional Upper-GI MDTM was associated with an increase in patients discussed with a resection centre, more curative resections and a better OS. It remains to be elucidated which factors in the clinical pathway explain this observed improved survival.
Subject(s)
Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/therapy , Patient Care Team/standards , Videoconferencing , Aged , Decision Making , Esophageal Neoplasms/mortality , Female , Humans , Interdisciplinary Communication , Male , Middle Aged , Netherlands , Prognosis , Registries , Survival RateABSTRACT
BACKGROUND: Metastatic colorectal cancer patients with deficient mismatch repair (dMMR mCRC) benefit from immunotherapy. Interpretation of the single-arm immunotherapy trials is complicated by insignificant survival data during systemic non-immunotherapy. We present survival data on a large, comprehensive cohort of dMMR mCRC patients, treated with or without systemic non-immunotherapy. METHODS: Two hundred and eighty-one dMMR mCRC patients (n = 54 from three prospective Phase 3 CAIRO trials; n = 227 from the Netherlands Cancer Registry). Overall survival was analysed from diagnosis of mCRC (OS), from initiation of first-line (OS1) and second-line (OS2) systemic treatment. Cox regression analysis examined prognostic factors. As comparison for OS 2746 MMR proficient mCRC patients were identified. RESULTS: Of 281 dMMR patients, 62% received first-line and 26% second-line treatment. Median OS was 16.0 months (13.8-19.6) with antitumour therapy and 2.5 months (1.8-3.5) in untreated patients. OS1 was 12.8 months (10.7-15.2) and OS2 6.2 months (5.4-8.9) in treated dMMR patients. Treated dMMR patients had a 7.6-month shorter median OS than pMMR patients. CONCLUSION: Available data from immunotherapy trials lack a control arm with standard systemic treatment. Given the poor outcome compared to the immunotherapy results, our data strongly suggest a survival benefit of immunotherapy in dMMR mCRC patients.
Subject(s)
Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Microsatellite Instability , Adult , Aged , Colorectal Neoplasms/mortality , DNA Mismatch Repair , Female , Humans , Male , Middle Aged , Survival AnalysisABSTRACT
The combination of exemestane and everolimus is a new treatment option for metastatic hormone-sensitive breast cancer. This treatment is used after progression on non-steroidal aromatase inhibitors. The treatment is generally well tolerated, but sometimes leads to minor or even serious side effects. It is important to be aware of these side effects and to treat them. We describe two patients who had to cope with various forms of toxicity: a 73-year-old woman with aphthous mouth lesions and a 49-year-old woman with pneumonitis. We then discuss the efficacy of the combination exemestane and everolimus and its positioning in the treatment of metastatic hormone-sensitive breast cancer. Finally, some common and some potentially serious side effects will be discussed, along with recommendations for their management and indications for distinguishing side effects from disease progression.
