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Breast Cancer

Breast Cancer With Chest Wall Progression: Treatment With Photodynamic Therapy

Author(s): Rosa E. Cuenca, MD, Ron R. Allison, MD, Claudio Sibata, PhD, and Gordon H. Downie, MD, PhD

Background
Chest wall progression of breast carcinoma affects up to 5% of breast cancer patients and is a major source of their pain. Treatment options are limited or may not be offered to these patients. Low-dose Photofrin-induced photodynamic therapy (PDT) offers an excellent clinical response with minimal morbidity. We report our continued experience with PDT in this setting.

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Early neoplastic and metastatic mammary tumours of transgenic mice detected by 5-aminolevulinic acid-stimulated protoporphyrin IX accumulation

Author(s): A M Dorward, K S Fancher, T M Duffy, W G Beamer and H Walt

Abstract
A photodynamic technique for human breast cancer detection founded upon the ability of tumour cells to rapidly accumulate the fluorescent product protoporphyrin IX (PpIX) has been applied to transgenic mouse models of mammary tumorigenesis. A major goal of this investigation was to determine whether mouse mammary tumours are reliable models of human disease in terms of PpIX accumulation, for future mechanistic and therapeutic studies. The haeme substrate 5-aminolevulinic acid (5-ALA) (200 mg kg-1) was administered to mouse strains that develop mammary tumours of various histological subtypes upon expression of the transgenic oncogenes HRAS, Polyoma Virus middle T antigen, or Simian Virus 40 large T antigen in the mammary gland. Early neoplastic lesions, primary tumours and metastases showed consistent and rapid PpIX accumulation compared to the normal surrounding tissues, as evidenced by red fluorescence (635 nm) when the tumours were directly illuminated with blue light (380440 nm). Detection of mouse mammary tumours at the stage of ductal carcinoma in situ by red fluorescence emissions suggests that enhanced PpIX synthesis is a good marker for early tumorigenic processes in the mammary gland. We propose the mouse models provide an ideal experimental system for further investigation of the early diagnostic and therapeutic potential of 5-ALA-stimulated PpIX accumulation in human breast cancer patients.

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Photodynamic Detection of Mammary Cancer

Author(s): Dr. Ann Dorward, Assistant Professor, Canada Research Chair in Genetics, Faculty of Medicine, Dr. Heinrich Walt, University Hospital Zurich

Abstract
Epithelial-derived tumours share the biochemical property of increased production and retention of protoporphyrin IX (PpIX), the immediate biochemical precursor of heme, following administration of the rate-limiting substrate 5-aminolevulinic acid (5-ALA). PpIX is a naturally fluorescent molecule that emits red light under blue light excitation, and thus tumour-selective loading of PpIX following 5-ALA administration is under consideration as a photodetection and photodiagnostic tool in anatomical areas where light administration and detection are endoscopically feasible, such as the colon, oral cavity and bladder. PpIX loading following oral administration of 5-ALA has also been shown as a sensitive photodetection method for visualizing human breast tumour margins during surgery, and the histological identification of lymph node metastases. In collaboration with Dr. Heinrich Walt of University Hospital Zurich and Cancer Network Zurich, a follow up survey of mammary tumours from several transgenic mouse strains revealed a similar pattern of rapid PpIX loading following a single iv injection of 5-ALA. Like human patients, PpIX fluorescence was useful for identification of metastases and surprisingly, very early stages of ductal carcinoma in situ. Future efforts on this project will consider the significance of PpIX biochemistry to tumour development, and the opportunities afforded by this generalized tumour-marker to design non-invasive imaging strategies that are useful for early detection of solid tumours.

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