In addition to being a risk factor for breast cancer, breast density has been hypothesized to be a surrogate biomarker for predicting response to endocrine-based chemotherapies. The purpose of this study was to evaluate whether a non-invasive bedside scanner based on diffuse optical spectroscopic imaging (DOSI) provides quantitative metrics to measure and track changes in breast tissue composition and density. In order to access a broad range of densities in a limited patient population, we performed optical measurements on the contralateral normal breast of patients before and during neoadjuvant chemotherapy (NAC). In this work, DOSI parameters, including tissue hemoglobin, water, and lipid concentrations were obtained and correlated with magnetic resonance imaging (MRI)-measured fibroglandular tissue density. We evaluate how DOSI could be used to assess breast density while gaining new insight into the impact of chemotherapy on breast tissue.

This was a retrospective study of 28 volunteers undergoing NAC treatment for breast cancer. 3.0T MRI and broadband DOSI (650-1000nm) were obtained from the contralateral normal breast before and during NAC. Longitudinal DOSI measurements were used to calculate breast tissue concentrations of oxygenated and deoxygenated hemoglobin, water, and lipid. These values were compared to MRI-measured fibroglandular density before and during therapy.

Water (r=0.843, p<0.001), deoxyhemoglobin (r=0.785, p=0.003), and lipid (r=-0.707, p=0.010) concentration measured by DOSI correlated strongly with MRI-measured density prior to therapy. Mean DOSI parameters differed significantly between pre- and post-menopausal subjects at baseline (water: p<0.001, deoxyhemoglobin: p=0.024, lipid: p=0.006). During NAC treatment measured at ~90 days, significant reductions were observed in oxyhemoglobin for pre- (-20.0%, 95% confidence interval (CI): -32.7 to -7.4) and post-menopausal subjects (-20.1%, 95% CI: -31.4 to -8.8), and water concentration for pre-menopausal subjects (-11.9%, 95% CI: -17.1 to -6.7) compared to baseline. Lipid increased slightly in pre-menopausal subjects (3.8%, 95% CI: 1.1 to 6.5) and water increased slightly in post-menopausal subjects (4.4%, 95% CI: 0.1 to 8.6). Percent change in water at the end of therapy compared to baseline correlated strongly with percent change in MRI-measured density (r=0.864, p=0.012).

DOSI functional measurements correlate with MRI fibroglandular density, both prior to therapy and during NAC. Though a limited patient data set, these results suggest that DOSI may provide new functional indices of density based on hemoglobin and water that could be used at the bedside to assess response to therapy and evaluate disease risk.