O'Sullivan Thomas D, Leproux Anaïs, Chen Jeon-Hor, Bahri Shadfar, Matlock Alex, Roblyer Darren, McLaren Christine E, Chen Wen-Pin, Cerussi Albert E, Su Min-Ying, Tromberg Bruce J
Breast Cancer Res. 2013 Feb 22;15(1):R14. doi: 10.1186/bcr3389.
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 noninvasive bedside scanner based on diffuse optical spectroscopic imaging (DOSI) provides quantitative metrics to measure and track changes in breast tissue composition and density. 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 evaluated 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. Both 3.0-T MRI and broadband DOSI (650 to 1,000 nm) 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 with 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 with DOSI correlated strongly with MRI-measured density before therapy. Mean DOSI parameters differed significantly between pre- and postmenopausal subjects at baseline (water, P < 0.001; deoxyhemoglobin, P = 0.024; lipid, P = 0.006). During NAC treatment measured at about 90 days, significant reductions were observed in oxyhemoglobin for pre- (-20.0%; 95% confidence interval (CI), -32.7 to -7.4) and postmenopausal subjects (-20.1%; 95% CI, -31.4 to -8.8), and water concentration for premenopausal subjects (-11.9%; 95% CI, -17.1 to -6.7) compared with baseline. Lipid increased slightly in premenopausal subjects (3.8%; 95% CI, 1.1 to 6.5), and water increased slightly in postmenopausal subjects (4.4%; 95% CI, 0.1 to 8.6). Percentage change in water at the end of therapy compared with baseline correlated strongly with percentage change in MRI-measured density (r = 0.864; P = 0.012).
DOSI functional measurements correlate with MRI fibroglandular density, both before therapy and during NAC. Although from a limited patient dataset, 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.
除了作为乳腺癌的一个风险因素外,乳腺密度还被假设为预测基于内分泌的化疗反应的替代生物标志物。本研究的目的是评估基于漫射光光谱成像(DOSI)的无创床边扫描仪是否能提供定量指标来测量和跟踪乳腺组织成分和密度的变化。为了在有限的患者群体中获取广泛的密度范围,我们在新辅助化疗(NAC)之前和期间对患者的对侧正常乳腺进行了光学测量。在这项工作中,获得了包括组织血红蛋白、水和脂质浓度在内的DOSI参数,并将其与磁共振成像(MRI)测量的纤维腺组织密度相关联。我们评估了DOSI如何用于评估乳腺密度,同时深入了解化疗对乳腺组织的影响。
这是一项对28名接受乳腺癌NAC治疗的志愿者的回顾性研究。在NAC之前和期间,从对侧正常乳腺获取3.0-T MRI和宽带DOSI(650至1000 nm)。纵向DOSI测量用于计算乳腺组织中氧合血红蛋白、脱氧血红蛋白、水和脂质的浓度。将这些值与治疗前和治疗期间MRI测量的纤维腺密度进行比较。
治疗前,DOSI测量的水(r = 0.843;P < 0.001)、脱氧血红蛋白(r = 0.785;P = 0.003)和脂质(r = -0.707;P = 0.010)浓度与MRI测量的密度密切相关。绝经前和绝经后受试者在基线时的平均DOSI参数有显著差异(水,P < 0.001;脱氧血红蛋白,P = 0.024;脂质,P = 0.006)。在约90天进行NAC治疗期间,与基线相比,绝经前(-20.0%;95%置信区间(CI),-32.7至-7.4)和绝经后受试者(-20.1%;95% CI,-31.4至-8.8)的氧合血红蛋白以及绝经前受试者的水浓度(-11.9%;95% CI,-17.1至-6.7)均有显著降低。绝经前受试者的脂质略有增加(3.8%;95% CI,1.1至6.5),绝经后受试者的水略有增加(4.4%;95% CI,0.1至8.6)。治疗结束时水的百分比变化与基线相比与MRI测量密度的百分比变化密切相关(r = 0.864;P = 0.012)。
DOSI功能测量在治疗前和NAC期间均与MRI纤维腺密度相关。尽管来自有限的患者数据集,但这些结果表明DOSI可能基于血红蛋白和水提供新的密度功能指标,可在床边用于评估治疗反应和评估疾病风险。