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    Optical Transillumination Spectroscopy For Monitoring Breast Cancer Risk Changes

    Scientific Abstract:
    Preventive Oncology can be split into 2 major tasks, identifying a person at risk towards a specific disease and providing an risk reducing intervention that affects the quality of life least while providing adequate risk reduction for the population at risk. Both tasks suffer by good techniques to identify the risk population with a very high odds ratio and monitor the efficacy of the intervention. Specifically efficacy monitoring has to relay on some physical or biochemical measurements as the genetic or demographic information about the individual undergoing the treatment will not be changed by it. We have shown previously that Optical transillumination spectroscopy (OTS) can be used to quantify the parenchymal breast tissue density with a correlation coefficient of > 0.8, providing information about changes in the tissue composition. Additionally OTS provides information about the light scattering, tissue chromophores concentrations, such as hemoglobin, oxyhemoglobin, water, lipids and other optical active biomolecules, thus providing more metabolic and structural information than for example mammography. The study design follows a longitudinal Case-Control study. We propose to recruit women of less than ~45 years of age who are planning their first pregnancy through a Toronto fertility clinic and we will monitor the breast tissue optically them for up to 3 years prior to fertility treatment, during the hormone treatment, pregnancy and breast feeding in approximately 3 month intervals. A control group of nulliparous women will be recruited through the University of Toronto Community and will also be monitored optically at the same frequency and interval. Interpretation of the spectra can be achieved in term of parenchymal tissue density, and tissue chromophores and light scattering power and amplitude. Thus, this set of optical transillumination spectra obtained during this study (e.g. nulliparous, versus 1st pregnancy women) will enable possible indicators for cancer protection because of their long term change post pregnancy and/or breastfeeding.

    Lay Abstract:
    As our knowledge about the associations between certain risk factors and targets increases, strategies for breast cancer prevention are attracting more attention in the scientific and clinical communities and most certainly from the consumer at large. However, the community wide and clinical implementation of these strategies for prevention requires two independent tasks. First a method to identify women most likely to benefit from risk reduction interventions with high sensitivity and specificity, and secondly a method permitting monitoring of the efficacy of the risk reduction intervention itself. The development of such a method will empower women, with the support of her physician, to judge the benefit of the intervention strategy in relation to the restriction(s) it imposes on her lifestyle. Regarding the first task, we have demonstrated that Optical Transillumination Spectroscopy (OTS) can classify parenchymal breast tissue densities, the best known physical risk assessment technique with a sensitivity and specificity of over 0.97 each, thus providing at least a similar high odds ratio as parenchymal tissue density to cancer risk, without the adverse effect of using ionizing radiation. The second task, development of a physical assessment technique to monitor the efficacy of any given intervention strategy is the basis of this application. OTS is a non invasive, and harmless procedure due to the use of non-ionizing radiation only, thus frequent measurements are possible. It is a physical measurement and transillumination spectra have been shown to contain information about tissue density and tissue composition, such as water, lipid, hemoglobin, and other biomolecules. Additionally OTS can be applied to dense breast tissue. In order to demonstrate the technique’s ability to monitor changes in breast tissue composition resulting from an event associated with reducing breast cancer risk, we elected pregnancy, childbirth and breastfeeding as a model system. This model has the advantage of employing a (mostly) natural process shown to carry an odds ratio of 2 relative to breast cancer(when the first child is born early in life) even over multiple decades. By recruiting the participants through a fertility clinic one can also monitor short term changes in the breast tissue that are assumed to increase breast cancer risk, here hormonal exposure prior to artificial insemination or in vitro fertilization.