Clinicopathological and prognostic impact of imaging of breast cancer angiogenesis and hypoxia using diffuse optical spectroscopy

Abstract

Near-infrared diffuse optical spectroscopy (DOS) imaging can non-invasively measure tumor hemoglobin concentration using high contrast to normal tissue, thus providing vascularity and oxygenation status. We assessed the clinical usefulness of DOS imaging in primary breast cancer. In all, 118 women with a histologically confirmed diagnosis of primary malignant tumor were enrolled. All participants underwent testing using time-resolved DOS before treatment initiation. Visual assessment of DOS imaging for detecting tumors was carried out by two readers blinded to the clinical data. Relative total hemoglobin (rtHb) and oxygen saturation (stO2) of the tumors was compared with clinicopathological variables and 10-year prognosis was calculated. Sensitivity for detecting a tumor based on the rtHb breast map was 62.7% (74/118). The sensitivity depended on T stage: 100% (7/7) for T3, 78.9% (45/57) for T2, 44.7% (17/38) for T1, and 31.3% (5/16) for Tis. Tumors showed unique features of higher rtHb with a wider range of stO2 than normal breast tissue, depending on histological type. There was a significant correlation of rtHb with tumor size, lymphatic vascular invasion, and histological grade, and of stO2 with age and tumor size. Neither rtHb nor stO2 correlated with intrinsic biomarkers such as estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2; rtHb inversely correlated with 10-year relapse-free survival and overall survival, with statistical significance. Diffuse optical spectroscopy imaging has limited utility for the early detection of breast cancer; nonetheless, the findings suggest that the degree of tumor angiogenesis and hypoxia may be associated with tumor aggressiveness and poor prognosis.

Early Therapeutic Prediction Based on Tumor Hemodynamic Response Imaging: Clinical Studies in Breast Cancer with Time-Resolved Diffuse Optical Spectroscopy

“…be significantly higher than those of the contralateral normal tissue ( Figure 3A) [34]. There were no significant differences in average rtHb levels among the various histological types such as ductal carcinoma in situ, invasive ductal carcinoma, invasive lobular carcinoma, or mucinous carcinoma.…”

“…In the initial study, we recruited 118 patients with an established histological diagnosis of breast carcinoma, and TRS-based values such as HbO 2 , HHb, tHb, and SO 2 of breast tumors were found to be significantly higher than those of the contralateral normal tissue ( Figure 3A) [34]. There were no significant differences in average rtHb levels among the various histological types such as ductal carcinoma in situ, invasive ductal carcinoma, invasive lobular carcinoma, or mucinous carcinoma.…”

Photoacoustic mammography capable of simultaneously acquiring photoacoustic and ultrasound images

“…The estimated area was positioned sufficiently far from the lesion of the tumor-bearing breast or the contralateral normal breast to avoid the effect of tumor-related blood vessels and to more precisely obtain the average optical properties of normal breast tissue. 31 We adopted μ a;b and μ s;b 0 values of 760 and 800 nm, respectively, in the TRS-20 to calculate the light fluence distribution at 756 and 797 nm. The light fluence distribution is appropriately calculated on the assumption the breast consists of homogeneous tissue and that the errors caused by the slight difference of wavelengths between measurements by TRS-20 and PAM-02, i.e., only several nanometers, are negligibly small.…”

“…Several clinical studies have reported promising results from diffuse optical tomography (DOT) for the differential diagnosis and therapeutic monitoring of breast cancer. [7][8][9] However, the clinical usefulness of DOT is currently limited because of its poor spatial resolution.…”

Assessing Oxygenation Response to Eribulin in a Patient with Recurrent Breast Cancer after Resistance to Endocrine Therapy

“…Investigators have reported FMISO uptake as a robust measure of intracellular hypoxia, and reduced hypoxic activity after endocrine therapy has been identified as a good predictive marker of clinical response in patients with HR-positive metastatic breast cancer [8]. Tissue hypoxia can also be noninvasively measured using Diffuse Optical Spectroscopic Imaging (DOSI) with near-infrared light, which can enhance the characterization of vascularity and tissue oxygenation [9].…”