Niccolai, Elena, Baldi, Simone, Nannini, Giulia, Gensini, Francesca, Papi, Laura, Vezzosi, Vania, Bianchi, Simonetta, Orzalesi, Lorenzo, Ramazzotti, Matteo, and Amedei, Amedeo
Background: Emerging evidence suggests that breast microbiota dysbiosis contributes to cancer initiation, progression, prognosis and treatment efficacy. Anyway, available data are referred only to female patients, and studies on males are completely missing. Male breast cancer (MBC) is 70–100 times less frequent, but the mortality rate adjusted to incidence is higher in men than in females. Currently, MBC diagnostic approaches and treatments have generally been extrapolated from the clinical experience gained in women, while few studies focus on characterizing male cancer biology. Taking into account the rising importance of the oncobiome field and the need of MBC targeted studies, we explored the breast cancer oncobiome of male and female patients. Methods: 16S rRNA gene sequencing was performed in 20 tumor and 20 non-pathological adjacent FFPE breast tissues from male and female patients. Results: We documented, for the first time, the presence of a sexually dimorphic breast-associated microbiota, here defined as "breast microgenderome". Moreover, the paired analysis of tumor and non-pathological adjacent tissues suggests the presence of a cancer-associated dysbiosis in male patients, with surrounding tissue conserving a healthier microbiome, whereas in female patients, the entire breast tissue is predisposed to cancer development. Finally, the phylum Tenericutes, especially the genera Mesoplasma and Mycobacterium, could to be involved in breast carcinogenesis, in both sexes, deserving further investigation, not only for its role in cancer development but even as potential prognostic biomarker. Conclusions: Breast microbiota characterization can enhance the understanding of male breast cancer pathogenesis, being useful for detection of new prognostic biomarkers and development of innovative personalized therapies, remarking the relevant gender differences. Plain Language Summary: Breast tissue can become inhabited by microbes through different pathways, and an uneven distribution of these microorganisms could potentially contribute to the development, prognosis, and treatment response of breast cancer. However, the current available data primarily focus on female patients, with a significant dearth of studies on males. To address this gap, the present study investigates the microbiota composition of both tumorous and healthy breast tissue samples from both male and female patients. The findings of this research highlight a disparity in the types of bacteria present in male and female breast tissue. Specifically, it shows that male patients with breast cancer have a higher imbalance of bacteria in the cancerous area compared to the surrounding healthy tissue. In contrast, in females the dysbiosis extend to the whole breast tissue. Moreover, the study identifies specific strains of bacteria that might potentially be involved in the development of breast cancer in both males and females. In conclusion, this study underscores the significance of microbial colonization in breast tissue and its potential influence on breast cancer in both males and females. By expanding our understanding of the microbial composition in breast cancer, we can pave the way for innovative diagnostic methods and treatment approaches for male breast cancer, while simultaneously advancing our knowledge of this complex disease. Highlights: Few studies have been conducted to describe male cancer biology in comparison with female breast cancer. For the first time, we discovered a sexually dimorphic breast-associated microbiome, termed "breast microgenderome". In females, the dysbiosis extend to the whole breast tissue, while in men, it appears to be confined to the tumor site. Tenericutes, particularly the genera Mesoplasma and Mycobacterium, may be implicated in breast carcinogenesis in both sexes. [ABSTRACT FROM AUTHOR]