Lee A, et al. Ann Lab Med. 2020 Mar;40(2):114-121. https://doi.org/10.3343/alm.2020.40.2.114

Yom CK, et al. J Breast Cancer. 2011 Dec;14(4):262-268. https://doi.org/10.4048/jbc.2011.14.4.262

The microbiome involved in the human estrogen metabolism is known as the estrobolome. This study aimed to show that the estrobolome can be used in breast cancer treatment. We first analyzed the blood microbiome composition of healthy controls and patients with breast cancer. In particular, we investigated the bacteria producing β−glucuronidase and/or β−galactosidase, which are involved in estrogen metabolism in the human body. Staphylococcus species were more abundant in healthy controls than in breast cancer patients and therefore were selected for further analyses. The effect of Staphylococcus aureus on endocrine therapy was analyzed by a combination treatment with tamoxifen. Analysis of the microbiome of blood samples showed that species producing β−glucuronidase were more abundant in breast cancer patients than in healthy controls. Further experiments confirmed that the efficacy of tamoxifen increased when administered in conjugation with the extracellular vesicles (EVs) of S. aureus. Based on our results, we deduced that S. aureus EVs could potentially be used as adjuvants for breast cancer treatment in the future.

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme involved in tumor immune escape. Blockade of the IDO1 pathway is an emerging modality of cancer immunotherapy. Triple-negative breast cancer (TNBC) lacks established therapeutic targets and may be a good candidate for this novel immunotherapeutic agent. The purpose of this study was to evaluate the clinicopathologic characteristics of the IDO1-expressing TNBC subset. A tissue microarray was constructed from 200 patients with TNBC. Immunohistochemistry (IHC) for IDO1 and TNBC molecular subtype-surrogate markers (AR, GCDFP-15, claudin-3, E-cadherin, CK5/6, and EGFR) was performed using this tissue microarray. Real-time polymerase chain reaction was performed to confirm the IDO1 mRNA expression level in 16 fresh-frozen TNBC samples. Two hundred TNBCs were classified into four subtypes based on surrogate IHC results: 22 luminal androgen receptor type (11.0%), 23 claudin-low type (11.4%), 103 basal-like type (51.5%), and 52 mixed type (26.0%). IDO1 positivity (defined as expression of >10% tumor cells) was observed in 37% of all TNBCs. IDO1 IHC expression was well correlated with mRNA expression. IDO1 positivity was significantly associated with smaller tumor size, dense stromal lymphocytic infiltration, and basal-like phenotype; however, it did not affect the patients' prognosis. IDO1 expression in basal-like TNBCs is considered an immune inhibitory signal that counterbalances active immunity and may reflect the high mutational load of these tumors. Our results suggest which patients with TNBC would be more efficaciously treated with IDO1 blockade.

The incidence of breast cancer (BC) is increasing in South Korea, and diet is closely related to the high prevalence of BC. The microbiome directly reflects eating habits. In this study, a diagnostic algorithm was developed by analyzing the microbiome patterns of BC. Blood samples were collected from 96 patients with BC and 192 healthy controls. Bacterial extracellular vesicles (EVs) were collected from each blood sample, and next-generation sequencing (NGS) of bacterial EVs was performed. Microbiome analysis of patients with BC and healthy controls identified significantly higher bacterial abundances using EVs in each group and confirmed the receiver operating characteristic (ROC) curves. Using this algorithm, animal experiments were performed to determine which foods affect EV composition. Compared to BC and healthy controls, statistically significant bacterial EVs were selected from both groups, and a receiver operating characteristic (ROC) curve was drawn with a sensitivity of 96.4%, specificity of 100%, and accuracy of 99.6% based on the machine learning method. This algorithm is expected to be applicable to medical practice, such as in health checkup centers. In addition, the results obtained from animal experiments are expected to select and apply foods that have a positive effect on patients with BC.