Precision of Raman spectroscopy measurements in detection of microcalcifications in breast needle biopsies

Microcalcifications are an early mammographic sign of breast cancer and a target for stereotactic breast needle biopsy. We developed Raman spectroscopy decision algorithms to detect breast microcalcifications, based on fit coefficients (FC) derived by modeling tissue Raman spectra as a linear combination of the Raman spectra of 9 chemical and morphologic components of breast tissue. However, little or no information is available on the precision of such measurements and its effect on the ability of Raman spectroscopy to make predictions for breast microcalcification detection. Here we report the precision, that is, the closeness of agreement between replicate Raman spectral measurements--and the model FC derived from them--obtained ex vivo from fresh breast biopsies from patients undergoing stereotactic breast needle biopsy, using a compact clinical Raman system. The coefficients of variation of the model FC averaged 0.03 for normal breast tissue sites, 0.12 for breast lesions without, and 0.22 for breast lesions with microcalcifications. Imprecision in the FC resulted in diagnostic discordance among replicates only for line-sitters, that is, tissue sites with FC values near the decision line or plane. The source of this imprecision and their implications for the use of Raman spectroscopy for guidance of stereotactic breast biopsies for microcalcifications are also discussed. In summary, we conclude that the precision of Raman spectroscopy measurements in breast tissue obtained using our compact clinical system is more than adequate to make accurate and repeatable predictions of microcalcifications in breast tissue using decision algorithms based on model FC. This provides strong evidence of the potential of Raman spectroscopy guidance of stereotactic breast needle biopsies for microcalcifications.