Division of Hematology and Medical Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
Breast Cancer Res Treat. 2021 Aug;189(1):297-304. doi: 10.1007/s10549-021-06320-6. Epub 2021 Jul 2.
Diffuse optical tomography breast imaging system (DOTBIS) non-invasively measures tissue concentration of hemoglobin, which is a potential biomarker of short-term response to neoadjuvant chemotherapy. We evaluated whether DOTBIS-derived measurements are modifiable with targeted therapies, including AKT inhibition and endocrine therapy.
We conducted a proof of principle study in seven postmenopausal women with stage I-III breast cancer who were enrolled in pre-surgical studies of the AKT inhibitor MK-2206 (n = 4) or the aromatase inhibitors exemestane (n = 2) and letrozole (n = 1). We performed DOTBIS at baseline (before initiation of therapy) and post-therapy in the affected breast (tumor volume) and contralateral, unaffected breast, and measured tissue concentrations (in μM) of total hemoglobin (ctTHb), oxyhemoglobin (ctOHb), and deoxyhemoglobin (ctHHb), as well as water fraction (%).
We found consistent decreases in DOTBIS-measured hemoglobin concentrations in tumor volume, with median percent changes for ctTHb, ctHHb, ctOHb, and water fraction for the entire cohort of - 27.1% (interquartile range [IQR] 37.5%), - 49.8% (IQR 29.3%), - 33.5% (IQR 47.4%), and - 3.6% (IQR 10.6%), respectively. In the contralateral breast, median percent changes for ctTHb, ctHHb, ctOHb, and water fraction were + 1.8% (IQR 26.7%), - 8.6% (IQR 29.3%), + 6.2% (IQR 29.5%), and + 1.9% (IQR 30.7%), respectively.
We demonstrated that DOTBIS-derived measurements are modifiable with pre-surgical AKT inhibition and endocrine therapy, supporting further investigation of DOTBIS as a potential imaging assessment of response to neoadjuvant targeted therapies in early stage breast cancer.
扩散光学断层成像乳腺成像系统(DOTBIS)无创性测量组织中血红蛋白的浓度,血红蛋白是新辅助化疗短期反应的潜在生物标志物。我们评估了 DOTBIS 衍生的测量值是否可以通过靶向治疗来改变,包括 AKT 抑制和内分泌治疗。
我们在 7 名绝经后患有 I-III 期乳腺癌的女性中进行了一项原理验证研究,这些女性参与了 AKT 抑制剂 MK-2206(n=4)或芳香酶抑制剂依西美坦(n=2)和来曲唑(n=1)的术前研究。我们在基线(治疗开始前)和治疗后在受影响的乳房(肿瘤体积)和对侧未受影响的乳房进行 DOTBIS,并测量组织浓度(以 μM 为单位)的总血红蛋白(ctTHb)、氧合血红蛋白(ctOHb)和脱氧血红蛋白(ctHHb),以及水分数(%)。
我们发现肿瘤体积中 DOTBIS 测量的血红蛋白浓度一致下降,整个队列的 ctTHb、ctHHb、ctOHb 和水分数的中位数百分比变化分别为-27.1%(四分位距 [IQR] 37.5%)、-49.8%(IQR 29.3%)、-33.5%(IQR 47.4%)和-3.6%(IQR 10.6%)。在对侧乳房中,ctTHb、ctHHb、ctOHb 和水分数的中位数百分比变化分别为+1.8%(IQR 26.7%)、-8.6%(IQR 29.3%)、+6.2%(IQR 29.5%)和+1.9%(IQR 30.7%)。
我们证明了 DOTBIS 衍生的测量值可以通过术前 AKT 抑制和内分泌治疗来改变,这支持了进一步研究 DOTBIS 作为新辅助靶向治疗早期乳腺癌反应的潜在成像评估。