Abstract P3-10-03: <i>Bartonella henselae</i> Infection Detected in Patients with Inflammatory Breast Cancer.
Authors: SV Fernandez, L Aburto, R Maggi, EB Breitschwerdt, M Cristofanilli
Journal: Cancer Research (2012)

Abstract Inflammatory breast cancer (IBC) is a very aggressive type of advanced breast cancer with a poor prognosis. Clinical symptoms involve a rapid onset of changes in the skin overlying the breast, including edema, redness and swelling including a wrinkled and orange peel appearance in the skin. This particular presentation is due to the invasion of the skin dermal lymphatics by breast cancer cells that obstructed the lymph channels producing the characteristic skin changes that mimic an inflammatory process. Mouse Mammary Tumor-associated Virus (MMTV) and other infectious agents have been consider as possible etiological agents of IBC particularly related to the initial description of higher incidence in women living in rural areas in North Africa. Although, the etiopathological 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. Several bacterial infections promote cell proliferation and could increase the rate of cell transformation. Bartonella spp. is an emerging pathogen that can cause conditions which are characterized by the development of proliferative lesions. Bartonella might cause vasculoproliferative disorders by triggering the proliferation of endothelial cells and inducing the secretion of proliferative cytokines from infected host cells. It cause persistent infection of erythrocytes and endothelial cells in their mammalian hosts and their transmission occur mainly by blood-sucking arthropods. Bartonella are Gram-negative bacteria usually associated with cat-scratch disease, urban trench fever, bacillary angiomatosis-peliosis and endocarditis. Some reports have showed some similarities between cat scratch disease and inflammatory breast cancer (Povoski et al., Breast J 9: 497–500, 2003). Methods and Results: In the present work, we report the identification of Bartonella henselae in the pleural effusions of two patients with IBC. These patients had both estrogen-receptor negative (ER−) and progesterone-receptor negative (PR−) disease and have failed a number of previous chemotherapy regimens. Furthermore, they had metastatic disease to the pleura, skin, lymph nodes and lung. Cells from the pleural fluids of these patients stained positive for Bartonella sp. using the Warthin-Starry staining kit. Moreover, we used PCR and sequencing of the 16S–23S intergenic spacer (ITS) region to identify the etiological agent as Bartonella henselae. By immunofluorescence using an antibody that specifically recognized Bartonella henselae, the bacteria were found in the nucleus of IBC tumor cells confirming the infection and their intracellular localization. Conclusions: These results suggested that bacteria infections such as the one produced by Bartonella henselae might contribute to the clinical and pathological characteristics of IBC, associated with rapid spread of the breast tumor cells through the lymphatic system. The infection and activation of endothelial lymphatics by Bartonella might contribute to the highly metastatic process observed in IBC patients. An acute inflammatory reaction triggered by the Bartonella infected endothelium may be crucial for initiating the chronic inflammation in IBC patients and the rapid spread of tumor cells. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-10-03.