Background: Attributed to inter-tumor heterogeneity, the therapeutic effect of salvage treatment is diverse and different malignant lesions might manifest various therapeutic responses among advanced breast cancer (ABC) patients. The present study aimed to explore the influence of the mode of lesion response on the subsequent treatment and to subclassify ABC patients for precise prognosis prediction.Methods: Based on the inclusion and exclusion criteria, ABC patients were retrospectively collected and followed up in the Guangdong Provincial Hospital of Chinese Medicine between 2018 and 2021.The treatment responses of all malignant lesions were evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Testing subclassified models were constructed based on different assembly mode of progressed malignant lesions for further classification of ABC patients experiencing disease progression following first-line treatment. Multivariate survival analyses were performed to assess the second-line progression-free survival (PFS) of various subgroups and screen the suitable classification model. The most suitable model was utilized to classify enrolled ABC patients as a heterogeneous progression-disease (Heter-PD) group or homogeneous progression-disease (Hom-PD) group. Univariate analysis and multivariate Cox regression survival analyses were performed to assess the prognostic value of each variable.Results: A total of 70 ABC patients experiencing disease progression after first-line treatment were enrolled into the analyses and underwent median follow-up of 10.36 months. We constructed 3 testing models and Model C (Hom-PD was defined when all the target and non-target lesions were evaluated as progression, with or without new lesions) could further distinguish ABC patients with worse survival. The second-line progression-free survival (PFS) times were significantly different between two groups (11.04 vs.6.07 months, P=0.034). For ABC patients retaining partial medication after disease progression of first-line treatment, the Heter-PD group showed a tendency of better second-line PFS than the Hom-PD group (13.18 vs. 3.61 months, P=0.430).Conclusions: Based on the disease progression mode after first-line treatment, the classification model could classify ABC patients as Hom-PD and Heter-PD subgroups, which manifest distinct prognoses during the sequential treatment. For Heter-PD patients, retainment of partial medication might be a rational choice for second-line therapy.
Background Emerging evidence has revealed the novel role of gut microbiota in the development of cancer, and it has been reported that gut microbiota of breast cancer patients displayed certain characteristics. However, direct causation between gut microbiota and breast cancer remains uncertain. Results In the present study, it was found that Prevotalla is a significantly enriched and prevalent genus in gut microbiota of breast cancer patients. Prevotella copri is the dominate species of Prevotalla genus in gut microbiota. Prior-oral administration of P. copri could promote breast cancer growth in specific germ-free (SPF) mice and germ-free (GF) mice. Mechanistically, the excess P. copri consumed large amount of tryptophan (Trp), thus hampering the physiological accumulation of indol-3-pyruvid acid (IPyA) in host, in which the energy-controlling AMPK signaling pathway was inactivated by UHRF1-regulated DNA methylation as indicated by the alternation in profiles of protein expression and DNA methylation. As discovered in our data, IPyA is an intrinsic anti-cancer reagent in host at physiological level, and such potent cytotoxicity on breast cancer cells is mainly relied on the activation of AMPK via suppressing UHRF1-mediated negative regulation, which was just opposite to the effect of P. copri on tumor growth. Conclusions The exhaustion of IPyA by excess P. copri makes great contribution to the promotion of breast cancer. Our findings, for the first time, highlighted P. copri as a risk factor in development of breast cancer.
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