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  • Choosing the best therapy for breast cancer

BioPhotonics
Jul 2009
Gary Boas, gboas@eggship-media.com

DURHAM, N.C. – A new system based on diffuse reflectance spectroscopy could help doctors decide the best treatment for breast cancer patients. A group at Duke University has shown that measuring the oxygen status in the microenvironment of a tumor can shed light on how aggressive the tumor will be and thus suggest which therapy might be most effective against it.

The researchers did not set out to aid oncologists in choosing the best treatment option. Initially, they sought to establish optical spectroscopy in the visible wavelength range as an adjunct to core-needle biopsy, a procedure in which the breast is literally penetrated with a needle to remove suspected tumor tissue for further analysis. Typically, ultrasound and stereotactic mammography are used to guide the needle. The researchers’ idea was that spectroscopy would provide additional information about oxygenation of the tissue because tumor growth is typically characterized by hypoxia, or low oxygen tension.

The problem, said J. Quincy Brown, a postdoctoral fellow in the lab of Nirmala Ramanujam, associate professor of biomedical engineering at Duke’s Pratt School of Engineering, was that most women who undergo core-needle biopsy of the breast do not have cancer, “so the yield of malignant tissues was very low.” As a result, Brown and colleagues found it difficult to validate use of optical spectroscopy to aid in diagnosis.

The investigators began looking at women who were undergoing surgery for the cancer, to achieve a higher cancer yield. But as they started collecting data, a perhaps more important goal emerged: obtaining further information about the micro-environment of the tumor that could guide decisions about which therapy to use. “What if we could tell the oncologist that this tumor has less oxygen than another tumor,” Brown said, “and then use that to impact the treatment decision?”

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Researchers have integrated an optical probe into a core-needle biopsy system to enable optical spectroscopy in the visible range during biopsy of the breast. This setup provides them with information about the oxygenation status of the tissue, which can help to determine the best therapy for treating any tumors they find.

Brown noted that there is considerable variability in the oxygenation of breast cancers. Many cancers stimulate growth of new blood vessels to ship oxygen to tumors; however, more aggressive tumors tend to thrive in low-oxygen environments. In the study, the researchers found that tumor oxygen content was correlated with the expression of the HER2/neu receptor, which is associated with more aggressive tumors. Knowing the oxygenation status therefore can help determine what kind of cancer it is and what sort of treatment is most appropriate.

Detecting changes in oxygenation status is relatively straightforward, Brown said; it is mostly a matter of integrating an optical probe into the core-needle biopsy system. The challenge here was in acquiring quantitative measurements. The researchers achieved this by implementing an inverse Monte Carlo model, which allowed them to decouple absorption from scattering in the measurements. This method enabled them to record increases and decreases in oxygenation and thus to provide quantitative information about the underlying physiology in breast cancer.

The researchers hope to do more, however, than simply provide a tool that can measure changes in tissue oxygenation. “What we really want to do,” Brown said, “is to demonstrate that knowing the environment of a tumor can have relevant implications in how the tumor is treated.” To this end, they have begun a pilot study in which they will measure the oxygenation status of a tumor during image-guided biopsy and examine its association with therapeutic response. Many patients do not respond to chemotherapy, but this may not become clear until after six weeks or more of treatment. The researchers hope to develop a predictive tool that will identify those not likely to respond, even before the therapy has begun.


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