Breast cancer (BC) is the most frequently occurring malignancy and the second cancer-specific cause of mortality in women in developed countries. Over 70% of the total number of BCs are hormone receptor-positive (HR+), and elevated levels of circulating estrogen (E) in the blood have been shown to be a major risk factor for the development of HR+ BC. This is attributable to estrogen’s contribution to increased cancer cell proliferation, stimulation of angiogenesis and metastasis, and resistance to therapy. The E metabolism–gut microbiome axis is functional, with subjacent individual variations in the levels of E. It is conceivable that the estrobolome (bacterial genes whose products metabolize E) may contribute to the risk of malignant neoplasms of hormonal origin, including BC, and may serve as a potential biomarker and target. It has been suggested that β-glucuronidase (GUS) enzymes of the intestinal microbiome participate in the strobolome. In addition, it has been proposed that bacterial GUS enzymes from the gastrointestinal tract participate in hormone BC. In this review, we discuss the latest knowledge about the role of the GUS enzyme in the pathogenesis of BC, focusing on (i) the microbiome and E metabolism; (ii) diet, estrobolome, and BC development; (iii) other activities of the bacterial GUS; and (iv) the new molecular targets for BC therapeutic application.

Breast cancer (BC) is the most common malignancy and the second cause of cancer specific death in women from high-income countries. More than 70% of all breast cancer are hormone receptor-positive BC, and elevated estrogen circulating in blood has been proved to be a strong risk for BC development. This is due to its contribution to enhance proliferation of cancerous cells, angiogenesis and metastasis stimulation and therapy resistance. The estrogen (E) metabolism–gut microbiome axis is functional with underlying individual variations in E levels. It is reasonable that the estrobolome (bacterial genes whose products are capable of metabolizing E) could contribute to the risk of hormone-driven malignancies including BC and may serve as a potential biomarker and target. Gut microbial β -glucuronidase (GUS) enzymes have been suggested to be involved in the estrobolome. Furthermore, bacterial GUS enzymes within the gastrointestinal tract have been postulated to contribute to hormone breast cancer. In this review, we discuss the recent knowledge about the role of GUS enzyme in the pathogenesis of breast cancer. We focus on the role of GUS in (i)-the microbioma and estrogen metabolism, (ii) diet, estrobolome, and the BC development, (iii) other activities of the bacterial β-glucuronidase, and (iv) the new molecular target for BC therapeutic application.

In triple-negative (TNBC) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer patients, neoadjuvant systemic therapy is the standard recommendation for tumors larger than 2 cm. Monitoring the response to primary systemic therapy allows for the assessment of treatment effects, the need for breast-conserving surgery (BCS), and the achievement of pathological complete responses (pCRs). In estrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer, the benefit of neoadjuvant strategies is controversial, as they have shown lower tumor downstaging and pCR rates compared to other breast cancers. In recent decades, several gene expression assays have been developed to tailor adjuvant treatments in ER+/HER2- early breast cancer (EBC) to identify the patients that will benefit the most from adjuvant chemotherapy (CT) and those at low risk who could be spared from undergoing CT. It is still a challenge to identify patients who will benefit from neoadjuvant systemic treatment (CT or endocrine therapy (ET)). Here, we review the published data on the most common gene expression signatures (MammaPrint (MP), BluePrint (BP), Oncotype Dx, PAM50, the Breast Cancer Index (BCI), and EndoPredict (EP)) and their ability to predict the response to neoadjuvant treatment, as well as the possibility of using them on core needle biopsies. Additionally, we review the changes in the gene expression signatures after neoadjuvant treatment, and the ongoing clinical trials related to the utility of gene expression signatures in the neoadjuvant setting.

Understanding the immune response to SARS-CoV-2 vaccination in cancer patients remains a critical priority given their immunocompromised status. In this prospective observational study, we evaluated humoral and cellular immunity across three time points—baseline, post-second dose, and post-booster—in 23 breast cancer patients undergoing active treatment. IgG antibody levels showed a significant increase following vaccination, with a 300-fold rise after the second dose and a 2200-fold increase post-booster, indicating a strong humoral response. CD19⁺ B cells also increased significantly, supporting B cell-mediated activation. Although overall T cell frequencies remained stable, we observed a shift toward memory phenotypes, with decreased naïve CD4⁺ and CD8⁺ T cells and increased central and peripheral memory subsets after the booster. Notably, CD8⁺ TEMRA cells expanded significantly, suggesting cytotoxic memory formation. Correlation analyses linked peripheral memory CD4⁺ T cells with anti-SARS-CoV-2 IgG titers, while CD8⁺ TEMRA cells showed an inverse association. Antigen-specific CD8⁺ T cell response was evaluated using APC-labeled MHC I Dextramer reagents. After the booster, 55.5% of patients developed detectable antigen-specific CD8⁺ T cells, whereas 44.5% did not. Importantly, one patient who failed to develop antigen-specific CD8⁺ T cells experienced a mild SARS-CoV-2 infection, suggesting that the absence of this response may increase susceptibility despite high IgG levels. These findings indicate that antigen-specific CD8⁺ T cell responses and antibody levels may act as complementary but not directly correlated arms of immunity. Microbiota profiling via sPLS-DA suggested weak but distinct microbial signatures associated with immune responsiveness, particularly enrichment of taxa such as Alistipes and Romoutsia among high-antibody responders. These findings emphasize that SARS-CoV-2 vaccination is immunogenic and well tolerated in breast cancer patients under therapy and highlight the need to further explore microbiota–immune interactions to optimize vaccination strategies in oncology.

1. Triple-negative breast cancer (TNBC) accounts for 15–20% of all breast cancers (BCs) and is among the most aggressive subtypes. 1 Defined by the absence of estrogen and progesterone receptors (E...