Abstract

Abstract Introduction: Inflammatory breast cancer (IBC) is a very aggressive variant of breast cancer with a poor prognosis.. Mouse Mammary Tumor-associated Virus (MMTV) and other infectious agents have been considered as possible etiological agents of IBC particularly related to the initial description of higher incidence in women living in rural areas in North Africa. The etiological role of bacteria in this disease has never been explored in spite of the evidence that chronic infections with certain bacteria can facilitate tumors development. We retrospectively evaluated tissue samples from patients with recurrent IBC to identify potential bacterial agents that could play a role in the development and progression of the disease. Methods: DNA was isolated from formalin-fixed paraffin embedded samples of 24 Inflammatory Breast Cancer (IBC) patients whose specimen had been submitted for genomic analysis using next-genomic sequencing (Foundation One™). An additional 3 non-IBC patients (lymph node, lung metastatic lesions) were included in the study. Unselected DNA libraries from these samples were pooled and sequenced on a HiSeq-2000 sequencer. Comparing the sequence data to a reference of 5,569 bacterial and viral genomic sequences identified the presence of Propionibacterium acnes, Ralstonia pickettii and Methylobacterium consequently, we enriched the DNA libraries for the presence of these species as well as bacterial rRNA genes using hybrid capture with synthesized oligonucleotide baits and sequenced the enriched libraries. Results: Twenty three IBC patients and 3 non-IBC breast cancer patients were included in the study. Tissue specimens included, 14 chest wall and skin;6 breast, 2 lymph nodes; 1 liver, 1 lung, 1 pleural fluid, 1 brain. In 16 out of the 23 IBC (70%) of specimens we detected bacteria DNA. Propionibacterium acnes were detected in 12 cases. Bartonella henselae was detected in 1 out of the 23 IBC specimens. Furthermore, additional detected species included Ralstonia pickettii (3 cases) and Pseudomonas aeruginosa (2). No bacteria were detected in samples from non-IBC breast cancer patients. Conclusions: In this study, we identified Propionibacterium acnes and Bartonella henselae in samples from IBC patients. The anaerobic Gram-positive bacterium P. acnes is ubiquitously found in sebaceous follicles of the human skin. Recent reports showed that P. acnes was present in a high number of cancerous prostate tissue samples. It has been suggested that P. acnes may be a contributing factor to the initiation or progression of prostate cancer. Bartonella is a Gram-negative bacteria usually associated with cat-scratch disease, urban trench fever, bacillary angiomatosis-peliosis and endocarditis. Some reports that have showed some similarities between cat scratch disease and inflammatory breast cancer. Our results suggested that P. acnes or Bartonella henselae infections might contribute to the clinical and pathological characteristics of IBC, associated with rapid spread of the breast tumor cells through the lymphatic system. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-12-07.

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