RESUMO
Cytotoxic chemotherapy with or without a combination of humanized monoclonal antibodies is regarded as the gold standard of personalized medicine for the treatment of breast cancer patients. Significant medication-related side effects are common accompanying phenomena for these patients, such as oral discomfort, mucositis, or even osteonecrosis of the jaw. In this study, we analyze the saliva samples of 20 breast cancer patients at three time points throughout their chemotherapy: at the baseline prior to treatment initiation (T1), after four-to-six cycles of chemotherapy (T2), and 1 year after the start of the treatment (T3) to investigate and characterize the long-term effects of chemotherapy on the oral microbiome. We aimed to characterize changes in the oral bacterial microbiome based on 16S rRNA gene amplicon analysis during chemotherapeutic treatment, as a potential target to treat common oral side effects occurring during therapy. The chemotherapeutic drugs used in our study for patient treatment were trastuzumab, docetaxel, pertuzumab, epirubicin, and cyclophosphamide. We find a significant increase in the relative abundance of potentially pathogenic taxa like Escherichia/Shigella and non-significant trends in the relative abundance of, for example, Actinomyces ssp. In conclusion, the role of microbiota in the oral side effects of chemotherapeutic treatment needs to be considered and should be analyzed in more detail using larger patient cohorts. Oral side effects in breast cancer patients undergoing chemotherapy are a common burden and should be treated for a better tolerability of the therapy.
RESUMO
OBJECTIVES: Pathophysiology of medication-related osteonecrosis of the jaw (MRONJ) is still unclear, and disease development is associated with adverse reaction of bisphosphonates and denosumab, and Actinomyces spp. as well. In this study, we evaluated the abundance of Actinomyces spp. in breast cancer patients undergoing chemotherapy compared to healthy controls. METHODS: Oropharyngeal samples were collected from treatment-naive early-stage breast cancer patients, who were scheduled for standard of care therapy (eight samples throughout chemotherapy, one prior to radiotherapy and one after a year of start), as well as from healthy controls at matched timepoints. We quantified Actinomyces spp. in the samples with a highly sensitive and specific quantitative polymerase chain reaction. RESULTS: Twenty-one patients and 16 healthy subjects were enrolled. Forty-eight percent of patients suffered from estrogen receptor-positive/progesterone receptor-positive or -negative/human epidermal growth factor receptor 2 (HER2)-negative disease, 38% were HER2-positive, and 14% were triple-negative. Comparison of Actinomyces spp. loads in cancer patients and healthy controls did not reveal significant difference. Fluctuations on bacterial quantity were observed in both groups over time. Tumor receptor status or different chemotherapy schemes of patients were not correlated with a particular pattern on abundance of Actinomyces spp. CONCLUSIONS: We suggest that Actinomyces spp. are not the initiative factors in MRONJ development. These bacteria are not altered in abundance during chemotherapy, but they behave opportunistic when there is a bone disruption in the oropharynx in the first place caused by antiresorptive drugs or dental trauma and proliferate in their new niche. Thus, Actinomyces spp. plays a latter role in MRONJ development, rather than a primary causative one.
